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Sample records for agranular frontal cortex

  1. Microcircuitry of agranular frontal cortex: contrasting laminar connectivity between occipital and frontal areas.

    PubMed

    Ninomiya, Taihei; Dougherty, Kacie; Godlove, David C; Schall, Jeffrey D; Maier, Alexander

    2015-05-01

    Neocortex is striking in its laminar architecture. Tracer studies have uncovered anatomical connectivity among laminae, but the functional connectivity between laminar compartments is still largely unknown. Such functional connectivity can be discerned through spontaneous neural correlations during rest. Previous work demonstrated a robust pattern of mesoscopic resting-state connectivity in macaque primary visual cortex (V1) through interlaminar cross-frequency coupling. Here we investigated whether this pattern generalizes to other cortical areas by comparing resting-state laminar connectivity between V1 and the supplementary eye field (SEF), a frontal area lacking a granular layer 4 (L4). Local field potentials (LFPs) were recorded with linear microelectrode arrays from all laminae of granular V1 and agranular SEF while monkeys rested in darkness. We found substantial differences in the relationship between the amplitude of gamma-band (>30 Hz) LFP and the phase of alpha-band (7-14 Hz) LFP between these areas. In V1, gamma amplitudes in L2/3 and L5 were coupled with alpha-band LFP phase in L5, as previously described. In contrast, in SEF phase-amplitude coupling was prominent within L3 and much weaker across layers. These results suggest that laminar interactions in agranular SEF are unlike those in granular V1. Thus the intrinsic functional connectivity of the cortical microcircuit does not seem to generalize across cortical areas. PMID:25744881

  2. Microcircuitry of Agranular Frontal Cortex: Testing the Generality of the Canonical Cortical Microcircuit

    PubMed Central

    Godlove, David C.; Maier, Alexander; Woodman, Geoffrey F.

    2014-01-01

    We investigated whether a frontal area that lacks granular layer IV, supplementary eye field, exhibits features of laminar circuitry similar to those observed in primary sensory areas. We report, for the first time, visually evoked local field potentials (LFPs) and spiking activity recorded simultaneously across all layers of agranular frontal cortex using linear electrode arrays. We calculated current source density from the LFPs and compared the laminar organization of evolving sinks to those reported in sensory areas. Simultaneous, transient synaptic current sinks appeared first in layers III and V followed by more prolonged current sinks in layers I/II and VI. We also found no variation of single- or multi-unit visual response latency across layers, and putative pyramidal neurons and interneurons displayed similar response latencies. Many units exhibited pronounced discharge suppression that was strongest in superficial relative to deep layers. Maximum discharge suppression also occurred later in superficial than in deep layers. These results are discussed in the context of the canonical cortical microcircuit model originally formulated to describe early sensory cortex. The data indicate that agranular cortex resembles sensory areas in certain respects, but the cortical microcircuit is modified in nontrivial ways. PMID:24719113

  3. Reflections on agranular architecture: predictive coding in the motor cortex

    PubMed Central

    Shipp, Stewart; Adams, Rick A.; Friston, Karl J.

    2013-01-01

    The agranular architecture of motor cortex lacks a functional interpretation. Here, we consider a ‘predictive coding’ account of this unique feature based on asymmetries in hierarchical cortical connections. In sensory cortex, layer 4 (the granular layer) is the target of ascending pathways. We theorise that the operation of predictive coding in the motor system (a process termed ‘active inference’) provides a principled rationale for the apparent recession of the ascending pathway in motor cortex. The extension of this theory to interlaminar circuitry also accounts for a sub-class of ‘mirror neuron’ in motor cortex – whose activity is suppressed when observing an action –explaining how predictive coding can gate hierarchical processing to switch between perception and action. PMID:24157198

  4. The importance of being agranular: a comparative account of visual and motor cortex

    PubMed Central

    Shipp, Stewart

    2005-01-01

    The agranular cortex is an important landmark—anatomically, as the architectural flag of mammalian motor cortex, and historically, as a spur to the development of theories of localization of function. But why, exactly, do agranularity and motor function go together? To address this question, it should be noted that not only does motor cortex lack granular layer four, it also has a relatively thinner layer three. Therefore, it is the two layers which principally constitute the ascending pathways through the sensory (granular) cortex that have regressed in motor cortex: simply stated, motor cortex does not engage in serial reprocessing of incoming sensory data. But why should a granular architecture not be demanded by the downstream relay of motor instructions through the motor cortex? The scant anatomical evidence available regarding laminar patterns suggests that the pathways from frontal and premotor areas to the primary motor cortex actually bear a greater resemblance to the descending, or feedback connections of sensory cortex that avoid the granular layer. The action of feedback connections is generally described as ‘modulatory’ at a cellular level, or ‘selective’ in terms of systems analysis. By contrast, ascending connections may be labelled ‘driving’ or ‘instructive’. Where the motor cortex uses driving inputs, they are most readily identified as sensory signals instructing the visual location of targets and the kinaesthetic state of the body. Visual signals may activate motor concepts, e.g. ‘mirror neurons’, and the motor plan must select the appropriate muscles and forces to put the plan into action, if the decision to move is taken. This, perhaps, is why ‘driving’ motor signals might be inappropriate—the optimal selection and its execution are conditional upon both kinaesthetic and motivational factors. The argument, summarized above, is constructed in honour of Korbinian Brodmann's centenary, and follows two of the fundamental

  5. Correlation Between Activation of the Prelimbic Cortex, Basolateral Amygdala, and Agranular Insular Cortex During Taste Memory Formation.

    PubMed

    Uematsu, Akira; Kitamura, Akihiko; Iwatsuki, Ken; Uneyama, Hisayuki; Tsurugizawa, Tomokazu

    2015-09-01

    Conditioned taste aversion (CTA) is a well-established learning paradigm, whereby animals associate tastes with subsequent visceral illness. The prelimbic cortex (PL) has been shown to be involved in the association of events separated by time. However, the nature of PL activity and its functional network in the whole brain during CTA learning remain unknown. Here, using awake functional magnetic resonance imaging and fiber tracking, we analyzed functional brain connectivity during the association of tastes and visceral illness. The blood oxygen level-dependent (BOLD) signal significantly increased in the PL after tastant and lithium chloride (LiCl) infusions. The BOLD signal in the PL significantly correlated with those in the amygdala and agranular insular cortex (IC), which we found were also structurally connected to the PL by fiber tracking. To precisely examine these data, we then performed double immunofluorescence with a neuronal activity marker (c-Fos) and an inhibitory neuron marker (GAD67) combined with a fluorescent retrograde tracer in the PL. During CTA learning, we found an increase in the activity of excitatory neurons in the basolateral amygdala (BLA) or agranular IC that project to the PL. Taken together, these findings clearly identify a role of synchronized PL, agranular IC, and BLA activity in CTA learning. PMID:24735672

  6. A heterogeneous population code for elapsed time in rat medial agranular cortex

    PubMed Central

    Matell, Matthew S.; Shea-Brown, Eric; Gooch, Cindy; Wilson, A. George; Rinzel, John

    2010-01-01

    The neural mechanisms underlying the temporal control of behavior are largely unknown. Here we recorded from the medial agranular cortex in rats trained to respond on a temporal production procedure for probabilistically available food reward. Due to variability in estimating the time of food availability, robust responding typically bracketed the expected duration, starting some time before and ending some time after the signaled delay. This response period provided an analytic “steady-state” window during which the subject actively timed their behavior. Remarkably, during these response periods, a variety of firing patterns were seen which could be broadly described as ramps, peaks, and dips, with different slopes, directions, and times at which maxima or minima occur. Regularized linear discriminant analysis indicated that these patterns provided sufficiently reliable information to discriminate the elapsed duration of responding within these response periods. Modeling this across neuron variability showed that the utilization of ramps, dips, and peaks with different slopes and minimal/maximal rates at different times led to a substantial improvement in temporal prediction errors, suggesting that heterogeneity in the neural representation of elapsed time may facilitate temporally controlled behavior. PMID:21319888

  7. Moderate Prenatal Alcohol Exposure Enhances GluN2B Containing NMDA Receptor Binding and Ifenprodil Sensitivity in Rat Agranular Insular Cortex

    PubMed Central

    Bird, Clark W.; Candelaria-Cook, Felicha T.; Magcalas, Christy M.; Davies, Suzy; Valenzuela, C. Fernando; Savage, Daniel D.; Hamilton, Derek A.

    2015-01-01

    Prenatal exposure to alcohol affects the expression and function of glutamatergic neurotransmitter receptors in diverse brain regions. The present study was undertaken to fill a current gap in knowledge regarding the regional specificity of ethanol-related alterations in glutamatergic receptors in the frontal cortex. We quantified subregional expression and function of glutamatergic neurotransmitter receptors (AMPARs, NMDARs, GluN2B-containing NMDARs, mGluR1s, and mGluR5s) by radioligand binding in the agranular insular cortex (AID), lateral orbital area (LO), prelimbic cortex (PrL) and primary motor cortex (M1) of adult rats exposed to moderate levels of ethanol during prenatal development. Increased expression of GluN2B-containing NMDARs was observed in AID of ethanol-exposed rats compared to modest reductions in other regions. We subsequently performed slice electrophysiology measurements in a whole-cell patch-clamp preparation to quantify the sensitivity of evoked NMDAR-mediated excitatory postsynaptic currents (EPSCs) in layer II/III pyramidal neurons of AID to the GluN2B negative allosteric modulator ifenprodil. Consistent with increased GluN2B expression, ifenprodil caused a greater reduction in NMDAR-mediated EPSCs from prenatal alcohol-exposed rats than saccharin-exposed control animals. No alterations in AMPAR-mediated EPSCs or the ratio of AMPARs/NMDARs were observed. Together, these data indicate that moderate prenatal alcohol exposure has a significant and lasting impact on GluN2B-containing receptors in AID, which could help to explain ethanol-related alterations in learning and behaviors that depend on this region. PMID:25747876

  8. Sexual differentiation of mammalian frontal cortex

    SciTech Connect

    Maggi, A.; Zucchi, I.

    1987-03-23

    The pattern of distribution of the progesterone binding sites was examined in selected nuclei of the brain of male and female rat. In female rats the frontal cortex resulted to be the region with the highest concentration of /sup 3/H R5020 biding sites. However, in male rats the same region showed very little progestin binding activity. When female rats were androgenized via neonatal exposure to testosterone, the progestin binding activity of the frontal cortex became similar to that observed in male rats. The present investigation indicates that sexual differentiation of the rat brain may include also brain regions not clearly involved in sex related functions like the frontal cortex. 30 references, 2 figures, 1 table.

  9. The scaling of frontal cortex in primates and carnivores

    PubMed Central

    Bush, Eliot C.; Allman, John M.

    2004-01-01

    Size has a profound effect on the structure of the brain. Many brain structures scale allometrically, that is, their relative size changes systematically as a function of brain size. Here we use independent contrasts analysis to examine the scaling of frontal cortex in 43 species of mammals including 25 primates and 15 carnivores. We find evidence for significant differences in scaling between primates and carnivores. Primate frontal cortex hyperscales relative to the rest of neocortex and the rest of the brain. The slope of frontal cortex contrasts on rest of cortex contrasts is 1.18 (95% confidence interval, 1.06-1.30) for primates, which is significantly greater than isometric. It is also significantly greater than the carnivore value of 0.94 (95% confidence interval, 0.82-1.07). This finding supports the idea that there are substantial differences in frontal cortex structure and development between the two groups. PMID:15007170

  10. Frontal cortex mediates unconsciously triggered inhibitory control.

    PubMed

    van Gaal, Simon; Ridderinkhof, K Richard; Fahrenfort, Johannes J; Scholte, H Steven; Lamme, Victor A F

    2008-08-01

    To further our understanding of the function of conscious experience we need to know which cognitive processes require awareness and which do not. Here, we show that an unconscious stimulus can trigger inhibitory control processes, commonly ascribed to conscious control mechanisms. We combined the metacontrast masking paradigm and the Go/No-Go paradigm to study whether unconscious No-Go signals can actively trigger high-level inhibitory control processes, strongly associated with the prefrontal cortex (PFC). Behaviorally, unconscious No-Go signals sometimes triggered response inhibition to the level of complete response termination and yielded a slow down in the speed of responses that were not inhibited. Electroencephalographic recordings showed that unconscious No-Go signals elicit two neural events: (1) an early occipital event and (2) a frontocentral event somewhat later in time. The first neural event represents the visual encoding of the unconscious No-Go stimulus, and is also present in a control experiment where the masked stimulus has no behavioral relevance. The second event is unique to the Go/No-Go experiment, and shows the subsequent implementation of inhibitory control in the PFC. The size of the frontal activity pattern correlated highly with the impact of unconscious No-Go signals on subsequent behavior. We conclude that unconscious stimuli can influence whether a task will be performed or interrupted, and thus exert a form of cognitive control. These findings challenge traditional views concerning the proposed relationship between awareness and cognitive control and stretch the alleged limits and depth of unconscious information processing. PMID:18685030

  11. The Organization of Dorsal Frontal Cortex in Humans and Macaques

    PubMed Central

    Mars, Rogier B.; Noonan, MaryAnn P.; Neubert, Franz-Xaver; Jbabdi, Saad; O'Reilly, Jill X.; Filippini, Nicola; Thomas, Adam G.; Rushworth, Matthew F.

    2013-01-01

    The human dorsal frontal cortex has been associated with the most sophisticated aspects of cognition, including those that are thought to be especially refined in humans. Here we used diffusion-weighted magnetic resonance imaging (DW-MRI) and functional MRI (fMRI) in humans and macaques to infer and compare the organization of dorsal frontal cortex in the two species. Using DW-MRI tractography-based parcellation, we identified 10 dorsal frontal regions lying between the human inferior frontal sulcus and cingulate cortex. Patterns of functional coupling between each area and the rest of the brain were then estimated with fMRI and compared with functional coupling patterns in macaques. Areas in human medial frontal cortex, including areas associated with high-level social cognitive processes such as theory of mind, showed a surprising degree of similarity in their functional coupling patterns with the frontal pole, medial prefrontal, and dorsal prefrontal convexity in the macaque. We failed to find evidence for “new” regions in human medial frontal cortex. On the lateral surface, comparison of functional coupling patterns suggested correspondences in anatomical organization distinct from those that are widely assumed. A human region sometimes referred to as lateral frontal pole more closely resembled area 46, rather than the frontal pole, of the macaque. Overall the pattern of results suggest important similarities in frontal cortex organization in humans and other primates, even in the case of regions thought to carry out uniquely human functions. The patterns of interspecies correspondences are not, however, always those that are widely assumed. PMID:23884933

  12. Specialized cortical subnetworks differentially connect frontal cortex to parahippocampal areas.

    PubMed

    Hirai, Yasuharu; Morishima, Mieko; Karube, Fuyuki; Kawaguchi, Yasuo

    2012-02-01

    How information is manipulated and segregated within local circuits in the frontal cortex remains mysterious, in part because of inadequate knowledge regarding the connectivity of diverse pyramidal cell subtypes. The frontal cortex participates in the formation and retrieval of declarative memories through projections to the perirhinal cortex, and in procedural learning through projections to the striatum/pontine nuclei. In rat frontal cortex, we identified two pyramidal cell subtypes selectively projecting to distinct subregions of perirhinal cortex (PRC). PRC-projecting cells in upper layer 2/3 (L2/3) of the frontal cortex projected to perirhinal area 35, while neurons in L5 innervated perirhinal area 36. L2/3 PRC-projecting cells partially overlapped with those projecting to the basolateral amygdala. L5 PRC-projecting cells partially overlapped with crossed corticostriatal cells, but were distinct from neighboring corticothalamic (CTh)/corticopontine cells. L5 PRC-projecting and CTh cells were different in their electrophysiological properties and dendritic/axonal morphologies. Within the frontal cortex, L2/3 PRC-projecting cells innervated L5 PRC-projecting and CTh cells with similar probabilities, but received feedback excitation only from PRC-projecting cells. These data suggest that specific neuron subtypes in different cortical layers are reciprocally excited via interlaminar loops. Thus, two interacting output channels send information from the frontal cortex to different hierarchical stages of the parahippocampal network, areas 35 and 36, with additional collaterals selectively targeting the amygdala or basal ganglia, respectively. Combined with the hierarchical connectivity of PRC-projecting and CTh cells, these observations demonstrate an exquisite diversification of frontal projection neurons selectively connected according to their participation in distinct memory subsystems. PMID:22302828

  13. The Dorsal Agranular Insular Cortex Regulates the Cued Reinstatement of Cocaine-Seeking, but not Food-Seeking, Behavior in Rats

    PubMed Central

    Cosme, Caitlin V; Gutman, Andrea L; LaLumiere, Ryan T

    2015-01-01

    Prior studies suggest that the insular cortex (IC), and particularly its posterior region (the PIc), is involved in nicotine craving and relapse in humans and rodents. The present experiments were conducted to determine whether the IC and its different subregions regulate relapse to cocaine-seeking behavior in rats. To address this issue, male Sprague–Dawley rats underwent cocaine self-administration followed by extinction training and reinstatement tests. Before each reinstatement, the PIc or the more anterior dorsal agranular IC (AId) was inactivated to determine their roles in the reinstatement to cocaine seeking. In contrast to the nicotine findings, PIc inactivation had no effect on cue-induced reinstatement for cocaine seeking. However, AId inactivation reduced cued reinstatement while having no effect on cocaine-prime reinstatement. AId inactivation had no effect on reinstatement of food-seeking behavior induced by cues, a food-prime, or cues+food-prime. Based on previous work hypothesizing a role for corticotropin-releasing factor (CRF) in the IC during craving and relapse, a subsequent experiment found that CRF receptor-1 (CRF1) blockade in the AId similarly reduced cued reinstatement. Our results suggest that the AId, along with CRF1 receptors in this region, regulates reinstatement to cocaine seeking, but not food seeking, depending on the type of reinstatement, whereas PIc activity does not influence cue-induced reinstatement. PMID:25837282

  14. Mechanisms of spatial attention control in frontal and parietal cortex.

    PubMed

    Szczepanski, Sara M; Konen, Christina S; Kastner, Sabine

    2010-01-01

    Theories of spatial attentional control have been largely based upon studies of patients suffering from visuospatial neglect, resulting from circumscribed lesions of frontal and posterior parietal cortex. In the intact brain, the control of spatial attention has been related to a distributed frontoparietal attention network. Little is known about the nature of the control mechanisms exerted by this network. Here, we used a novel region-of-interest approach to relate activations of the attention network to recently described topographic areas in frontal cortex [frontal eye field (FEF), PreCC/IFS (precentral cortex/inferior frontal sulcus)] and parietal cortex [intraparietal sulcus areas (IPS1-IPS5) and an area in the superior parietal lobule (SPL1)] to examine their spatial attention signals. We found that attention signals in most topographic areas were spatially specific, with stronger responses when attention was directed to the contralateral than to the ipsilateral visual field. Importantly, two hemispheric asymmetries were found. First, a region in only right, but not left SPL1 carried spatial attention signals. Second, left FEF and left posterior parietal cortex (IPS1/2) generated stronger contralateral biasing signals than their counterparts in the right hemisphere. These findings are the first to characterize spatial attention signals in topographic frontal and parietal cortex and provide a neural basis in support of an interhemispheric competition account of spatial attentional control. PMID:20053897

  15. Causal evidence for frontal cortex organization for perceptual decision making.

    PubMed

    Rahnev, Dobromir; Nee, Derek Evan; Riddle, Justin; Larson, Alina Sue; D'Esposito, Mark

    2016-05-24

    Although recent research has shown that the frontal cortex has a critical role in perceptual decision making, an overarching theory of frontal functional organization for perception has yet to emerge. Perceptual decision making is temporally organized such that it requires the processes of selection, criterion setting, and evaluation. We hypothesized that exploring this temporal structure would reveal a large-scale frontal organization for perception. A causal intervention with transcranial magnetic stimulation revealed clear specialization along the rostrocaudal axis such that the control of successive stages of perceptual decision making was selectively affected by perturbation of successively rostral areas. Simulations with a dynamic model of decision making suggested distinct computational contributions of each region. Finally, the emergent frontal gradient was further corroborated by functional MRI. These causal results provide an organizational principle for the role of frontal cortex in the control of perceptual decision making and suggest specific mechanistic contributions for its different subregions. PMID:27162349

  16. Causal evidence for frontal cortex organization for perceptual decision making

    PubMed Central

    Nee, Derek Evan; Riddle, Justin; Larson, Alina Sue; D’Esposito, Mark

    2016-01-01

    Although recent research has shown that the frontal cortex has a critical role in perceptual decision making, an overarching theory of frontal functional organization for perception has yet to emerge. Perceptual decision making is temporally organized such that it requires the processes of selection, criterion setting, and evaluation. We hypothesized that exploring this temporal structure would reveal a large-scale frontal organization for perception. A causal intervention with transcranial magnetic stimulation revealed clear specialization along the rostrocaudal axis such that the control of successive stages of perceptual decision making was selectively affected by perturbation of successively rostral areas. Simulations with a dynamic model of decision making suggested distinct computational contributions of each region. Finally, the emergent frontal gradient was further corroborated by functional MRI. These causal results provide an organizational principle for the role of frontal cortex in the control of perceptual decision making and suggest specific mechanistic contributions for its different subregions. PMID:27162349

  17. Differential Involvement of the Agranular vs Granular Insular Cortex in the Acquisition and Performance of Choice Behavior in a Rodent Gambling Task.

    PubMed

    Pushparaj, Abhiram; Kim, Aaron S; Musiol, Martin; Zangen, Abraham; Daskalakis, Zafiris J; Zack, Martin; Winstanley, Catharine A; Le Foll, Bernard

    2015-11-01

    Substance-related and addictive disorders, in particular gambling disorder, are known to be associated with risky decision-making behavior. Several neuroimaging studies have identified the involvement of the insular cortex in decision-making under risk. However, the extent of this involvement remains unclear and the specific contributions of two distinct insular subregions, the rostral agranular (RAIC) and the caudal granular (CGIC), have yet to be examined. Animals were trained to perform a rat gambling task (rGT), in which subjects chose between four options that differed in the magnitude and probability of rewards and penalties. In order to address the roles of the RAIC and CGIC in established choice behavior, pharmacological inactivations of these two subregions via local infusions of GABA receptor agonists were performed following 30 rGT training sessions. The contribution made by the RAIC or CGIC to the acquisition of choice behavior was also determined by lesioning these areas before behavioral training. Inactivation of the RAIC, but not of the CGIC, shifted rats' preference toward options with greater reward frequency and lower punishment. Before rGT acquisition, lesions of the RAIC, but not the CGIC, likewise resulted in a higher preference for options with greater reward frequency and lower punishment, and this persisted throughout the 30 training sessions. Our results provide confirmation of the involvement of the RAIC in rGT choice behavior and suggest that the RAIC may mediate detrimental risky decision-making behavior, such as that associated with addiction and gambling disorder. PMID:25953358

  18. Differential Involvement of the Agranular vs Granular Insular Cortex in the Acquisition and Performance of Choice Behavior in a Rodent Gambling Task

    PubMed Central

    Pushparaj, Abhiram; Kim, Aaron S; Musiol, Martin; Zangen, Abraham; Daskalakis, Zafiris J; Zack, Martin; Winstanley, Catharine A; Le Foll, Bernard

    2015-01-01

    Substance-related and addictive disorders, in particular gambling disorder, are known to be associated with risky decision-making behavior. Several neuroimaging studies have identified the involvement of the insular cortex in decision-making under risk. However, the extent of this involvement remains unclear and the specific contributions of two distinct insular subregions, the rostral agranular (RAIC) and the caudal granular (CGIC), have yet to be examined. Animals were trained to perform a rat gambling task (rGT), in which subjects chose between four options that differed in the magnitude and probability of rewards and penalties. In order to address the roles of the RAIC and CGIC in established choice behavior, pharmacological inactivations of these two subregions via local infusions of GABA receptor agonists were performed following 30 rGT training sessions. The contribution made by the RAIC or CGIC to the acquisition of choice behavior was also determined by lesioning these areas before behavioral training. Inactivation of the RAIC, but not of the CGIC, shifted rats' preference toward options with greater reward frequency and lower punishment. Before rGT acquisition, lesions of the RAIC, but not the CGIC, likewise resulted in a higher preference for options with greater reward frequency and lower punishment, and this persisted throughout the 30 training sessions. Our results provide confirmation of the involvement of the RAIC in rGT choice behavior and suggest that the RAIC may mediate detrimental risky decision-making behavior, such as that associated with addiction and gambling disorder. PMID:25953358

  19. Changes in rat frontal cortex gene expression following chronic cocaine.

    PubMed

    Freeman, Willard M; Brebner, Karen; Lynch, Wendy J; Patel, Kruti M; Robertson, Daniel J; Roberts, David C S; Vrana, Kent E

    2002-07-15

    Alterations in gene expression caused by repeated cocaine administration have been implicated in the long-term behavioral aspects of cocaine abuse. The frontal cortex mediates reinforcement, sensory, associative, and executive functions and plays an important role in the mesocortical dopamine reinforcement system. Repeated cocaine administration causes changes in frontal cortex gene expression that may lead to changes in the behaviors subserved by this brain region. Rats treated non-contingently with a binge model of cocaine (45 mg/kg/day, i.p.) for 14 days were screened for changes in relative mRNA abundance in the frontal cortex by cDNA hybridization arrays. To confirm changes, immunoreactive protein was measured (via protein-specific immunoblots) in a second group of identically-treated animals. Protein levels of protein tyrosine kinase 2 (PYK2), activity-regulated cytoskeletal protein (ARC), as well as an antigen related to nerve growth factor I-B (NGFI-B-RA) were shown to be significantly induced after cocaine administration. Levels of NGFI-B mRNA were confirmed by real-time RT-PCR to be increased with cocaine administration. These observations are similar to previously reported cocaine-responsive changes in gene expression but novel to the frontal cortex. This study also validates the use of hybridization arrays for screening of neuronal gene expression changes and the utility of relative protein quantification as a post-hoc confirmation tool. PMID:12117546

  20. Orbito-Frontal Cortex Is Necessary for Temporal Context Memory

    ERIC Educational Resources Information Center

    Duarte, Audrey; Henson, Richard N.; Knight, Robert T.; Emery, Tina; Graham, Kim S.

    2010-01-01

    Lesion and neuroimaging studies suggest that orbito-frontal cortex (OFC) supports temporal aspects of episodic memory. However, it is unclear whether OFC contributes to the encoding and/or retrieval of temporal context and whether it is selective for temporal relative to nontemporal (spatial) context memory. We addressed this issue with two…

  1. Role of Frontal Cortex in Attentional Capture by Singleton Distractors

    ERIC Educational Resources Information Center

    de Fockert, Jan W.; Theeuwes, Jan

    2012-01-01

    The role of frontal cortex in selective attention to visual distractors was examined in an attentional capture task in which participants searched for a unique shape in the presence or absence of an additional colour singleton distractor. The presence of the additional singleton was associated with slower behavioural responses to the shape target,…

  2. Frontal cortex BOLD signal changes in premanifest Huntington disease

    PubMed Central

    Ferraro, Stefania; Piacentini, Sylvie; Mandelli, Maria L.; Bertolino, Nicola; Ghielmetti, Francesco; Epifani, Francesca; Nigri, Anna; Taroni, Franco; Bruzzone, Maria G.; Donato, Stefano Di; Savoiardo, Mario; Mariotti, Caterina; Grisoli, Marina

    2014-01-01

    Objective: To identify a possible functional imaging biomarker sensitive to the earliest neural changes in premanifest Huntington disease (preHD), allowing early therapeutic approaches aimed at preventing or delaying clinical onset. Methods: Sixteen preHD and 18 healthy participants were submitted to anatomical acquisitions and functional MRI (fMRI) acquisitions during the execution of the exogenous covert orienting of attention task. Due to strong a priori hypothesis, all fMRI correlation analyses were restricted to the following: (1) the frontal oculomotor cortex identified by the means of a prosaccadic task, comprising frontal eye fields and supplementary frontal eye fields; and (2) the data collected during inhibition of return, a phenomenon occurring during the executed task. In preHD, multiple regression analysis was performed between fMRI data and the probability to develop the disease in the next 5 years (p5HD). Moreover, mean blood oxygen level–dependent (BOLD) signal changes in the frontal oculomotor cortex and striatal volumes were linearly correlated with p5HD. Results: In preHD, multiple regression analysis showed that clusters of activity strongly correlated with p5HD in the right frontal oculomotor cortex. Importantly, mean BOLD signal changes of this region correlated with p5HD (r2 = 0.52). Among the considered striatal volumes, a modest correlation (r2 = 0.29) was observed in the right putamen and p5HD. Conclusion: fMRI activations in the right-frontal oculomotor cortex during inhibition of return can be considered a possible functional imaging biomarker in preHD. PMID:24898924

  3. Responses of primate frontal cortex neurons during natural vocal communication

    PubMed Central

    Thomas, A. Wren; Nummela, Samuel U.; de la Mothe, Lisa A.

    2015-01-01

    The role of primate frontal cortex in vocal communication and its significance in language evolution have a controversial history. While evidence indicates that vocalization processing occurs in ventrolateral prefrontal cortex neurons, vocal-motor activity has been conjectured to be primarily subcortical and suggestive of a distinctly different neural architecture from humans. Direct evidence of neural activity during natural vocal communication is limited, as previous studies were performed in chair-restrained animals. Here we recorded the activity of single neurons across multiple regions of prefrontal and premotor cortex while freely moving marmosets engaged in a natural vocal behavior known as antiphonal calling. Our aim was to test whether neurons in marmoset frontal cortex exhibited responses during vocal-signal processing and/or vocal-motor production in the context of active, natural communication. We observed motor-related changes in single neuron activity during vocal production, but relatively weak sensory responses for vocalization processing during this natural behavior. Vocal-motor responses occurred both prior to and during call production and were typically coupled to the timing of each vocalization pulse. Despite the relatively weak sensory responses a population classifier was able to distinguish between neural activity that occurred during presentations of vocalization stimuli that elicited an antiphonal response and those that did not. These findings are suggestive of the role that nonhuman primate frontal cortex neurons play in natural communication and provide an important foundation for more explicit tests of the functional contributions of these neocortical areas during vocal behaviors. PMID:26084912

  4. Modulation of Orthographic Decoding by Frontal Cortex

    PubMed Central

    Whaley, Meagan Lee; Kadipasaoglu, Cihan Mehmet; Cox, Steven James

    2016-01-01

    Opinions are divided on whether word reading processes occur in a hierarchical, feedforward fashion or within an interactive framework. To critically evaluate these competing theories, we recorded electrocorticographic (ECoG) data from 15 human patients with intractable epilepsy during a word completion task and evaluated brain network dynamics across individuals. We used a novel technique of analyzing multihuman ECoG recordings to identify cortical regions most relevant to processing lexical information. The mid fusiform gyrus showed the strongest, earliest response after stimulus onset, whereas activity was maximal in frontal, dorsal lateral prefrontal, and sensorimotor regions toward articulation onset. To evaluate interregional functional connectivity, ECoG data from electrodes situated over specific cortical regions of interest were fit into linear multivariate autoregressive (MVAR) models. Spectral characteristics of the MVAR models were used to precisely reveal the timing and the magnitude of information flow between localized brain regions. This is the first application of MVAR for developing a comprehensive account of interregional interactions from a word reading ECoG dataset. Our comprehensive findings revealed both top-down and bottom-up influences between higher-level language areas and the mid fusiform gyrus. Our findings thus challenge strictly hierarchical, feedforward views of word reading and suggest that orthographic processes are modulated by prefrontal and sensorimotor regions via an interactive framework. SIGNIFICANCE STATEMENT Word reading is a critical part of everyday life. When the ability to read is disrupted, it can lead to learning disorders, as well as emotional and academic difficulties. The neural mechanisms underlying word reading are not well understood due to limitations in the spatial and temporal specificity of prior word reading studies. Our research analyzed data recorded from sensors implanted directly from surface of human

  5. Frontal cortex and the discovery of abstract action rules

    PubMed Central

    Badre, David; Kayser, Andrew S.; D’Esposito, Mark

    2010-01-01

    Summary Although we often encounter circumstances with which we have no prior experience, we rapidly learn how to behave in these novel situations. Such adaptive behavior relies on abstract behavioral rules that are generalizable, rather than concrete rules mapping specific cues to specific responses. Though the frontal cortex is known to support concrete rule learning, less well understood are the neural mechanisms supporting the acquisition of abstract rules. Here we use a novel reinforcement learning paradigm to demonstrate that more anterior regions along the rostro-caudal axis of frontal cortex support rule learning at higher levels of abstraction. Moreover, these results indicate that when humans confront new rule learning problems, this rostro-caudal division of labor supports the search for relationships between context and action at multiple levels of abstraction simultaneously. PMID:20435006

  6. FRONTAL AND PARIETAL CORTEX CONTRIBUTIONS TO ACTION MODIFICATION

    PubMed Central

    Mutha, Pratik K.; Stapp, Lee H.; Sainburg, Robert L.; Haaland, Kathleen Y.

    2014-01-01

    Successful achievement of task goals depends critically on the ability to adjust ongoing actions in response to environmental changes. The neural substrates underlying action modification have been a topic of great controversy: both, posterior parietal cortex and frontal regions, particularly prefrontal cortex have been previously identified as crucial in this regard, with most studies arguing in favor of one or the other. We aimed to address this controversy and understand whether frontal and parietal regions might play distinct roles during action modification. We tested ipsilesional arm performance of 27 stroke patients with focal lesions to frontal or parietal regions of the left or right cerebral hemisphere, and left or right arm performance of 18 healthy subjects on the classic double-step task in which a target is unpredictably displaced to a new location, requiring modification of the ongoing action. Only right hemisphere frontal lesions adversely impacted the timing of initiation of the modified response, while only left hemisphere parietal lesions impaired the accuracy of the modified action. Patients with right frontal lesions tended to complete the ongoing action to the initially displayed baseline target and initiated the new movement after a significant delay. In contrast, patients with left parietal damage did not accurately reach the new target location, but compared to the other groups, initiated the new action during an earlier phase of motion, before their baseline action was complete. Our findings thus suggest distinct, hemisphere specific contributions of frontal and parietal regions to action modification, and bring together, for the first time, disparate sets of prior findings about its underlying neural substrates. PMID:24763127

  7. Learning a New Selection Rule in Visual and Frontal Cortex.

    PubMed

    van der Togt, Chris; Stănişor, Liviu; Pooresmaeili, Arezoo; Albantakis, Larissa; Deco, Gustavo; Roelfsema, Pieter R

    2016-08-01

    How do you make a decision if you do not know the rules of the game? Models of sensory decision-making suggest that choices are slow if evidence is weak, but they may only apply if the subject knows the task rules. Here, we asked how the learning of a new rule influences neuronal activity in the visual (area V1) and frontal cortex (area FEF) of monkeys. We devised a new icon-selection task. On each day, the monkeys saw 2 new icons (small pictures) and learned which one was relevant. We rewarded eye movements to a saccade target connected to the relevant icon with a curve. Neurons in visual and frontal cortex coded the monkey's choice, because the representation of the selected curve was enhanced. Learning delayed the neuronal selection signals and we uncovered the cause of this delay in V1, where learning to select the relevant icon caused an early suppression of surrounding image elements. These results demonstrate that the learning of a new rule causes a transition from fast and random decisions to a more considerate strategy that takes additional time and they reveal the contribution of visual and frontal cortex to the learning process. PMID:27269960

  8. Learning a New Selection Rule in Visual and Frontal Cortex

    PubMed Central

    van der Togt, Chris; Stănişor, Liviu; Pooresmaeili, Arezoo; Albantakis, Larissa; Deco, Gustavo; Roelfsema, Pieter R.

    2016-01-01

    How do you make a decision if you do not know the rules of the game? Models of sensory decision-making suggest that choices are slow if evidence is weak, but they may only apply if the subject knows the task rules. Here, we asked how the learning of a new rule influences neuronal activity in the visual (area V1) and frontal cortex (area FEF) of monkeys. We devised a new icon-selection task. On each day, the monkeys saw 2 new icons (small pictures) and learned which one was relevant. We rewarded eye movements to a saccade target connected to the relevant icon with a curve. Neurons in visual and frontal cortex coded the monkey's choice, because the representation of the selected curve was enhanced. Learning delayed the neuronal selection signals and we uncovered the cause of this delay in V1, where learning to select the relevant icon caused an early suppression of surrounding image elements. These results demonstrate that the learning of a new rule causes a transition from fast and random decisions to a more considerate strategy that takes additional time and they reveal the contribution of visual and frontal cortex to the learning process. PMID:27269960

  9. Cascade of neural processing orchestrates cognitive control in human frontal cortex

    PubMed Central

    Tang, Hanlin; Yu, Hsiang-Yu; Chou, Chien-Chen; Crone, Nathan E; Madsen, Joseph R; Anderson, William S; Kreiman, Gabriel

    2016-01-01

    Rapid and flexible interpretation of conflicting sensory inputs in the context of current goals is a critical component of cognitive control that is orchestrated by frontal cortex. The relative roles of distinct subregions within frontal cortex are poorly understood. To examine the dynamics underlying cognitive control across frontal regions, we took advantage of the spatiotemporal resolution of intracranial recordings in epilepsy patients while subjects resolved color-word conflict. We observed differential activity preceding the behavioral responses to conflict trials throughout frontal cortex; this activity was correlated with behavioral reaction times. These signals emerged first in anterior cingulate cortex (ACC) before dorsolateral prefrontal cortex (dlPFC), followed by medial frontal cortex (mFC) and then by orbitofrontal cortex (OFC). These results disassociate the frontal subregions based on their dynamics, and suggest a temporal hierarchy for cognitive control in human cortex. DOI: http://dx.doi.org/10.7554/eLife.12352.001 PMID:26888070

  10. Occipital cortex of blind individuals is functionally coupled with executive control areas of frontal cortex.

    PubMed

    Deen, Ben; Saxe, Rebecca; Bedny, Marina

    2015-08-01

    In congenital blindness, the occipital cortex responds to a range of nonvisual inputs, including tactile, auditory, and linguistic stimuli. Are these changes in functional responses to stimuli accompanied by altered interactions with nonvisual functional networks? To answer this question, we introduce a data-driven method that searches across cortex for functional connectivity differences across groups. Replicating prior work, we find increased fronto-occipital functional connectivity in congenitally blind relative to blindfolded sighted participants. We demonstrate that this heightened connectivity extends over most of occipital cortex but is specific to a subset of regions in the inferior, dorsal, and medial frontal lobe. To assess the functional profile of these frontal areas, we used an n-back working memory task and a sentence comprehension task. We find that, among prefrontal areas with overconnectivity to occipital cortex, one left inferior frontal region responds to language over music. By contrast, the majority of these regions responded to working memory load but not language. These results suggest that in blindness occipital cortex interacts more with working memory systems and raise new questions about the function and mechanism of occipital plasticity. PMID:25803598

  11. Frontal cortex functioning in the infant broader autism phenotype.

    PubMed

    Holmboe, Karla; Elsabbagh, Mayada; Volein, Agnes; Tucker, Leslie A; Baron-Cohen, Simon; Bolton, Patrick; Charman, Tony; Johnson, Mark H

    2010-12-01

    Atypical attention has been proposed as a marker of the broader autism phenotype. In the present study we investigated this and the related process of inhibitory control at the youngest possible age through the study of infant siblings of children with an autism spectrum disorder (Sibs-ASD). Both attention and inhibition have been related to the frontal cortex of the brain. Nine- to ten-month-old Sibs-ASD and low-risk control infants completed the Freeze-Frame task, in which infants are encouraged to inhibit looks to peripherally presented distractors whilst looking at a central animation. The attractiveness of the central stimulus is varied in order to investigate the selectivity of infants' responses. In line with previous studies, it was found that a subset of Sibs-ASD infants had difficulty disengaging attention from a central stimulus in order to orient to a peripheral stimulus. The Sibs-ASD group also showed less Selective Inhibition than controls. However, Sibs-ASD infants did demonstrate Selective Inhibitory Learning. These results provide preliminary evidence for atypical frontal cortex functioning in the infant broader autism phenotype. PMID:20609478

  12. A Method for Recording Single-cell Activity in the Frontal Pole Cortex of Macaque Monkeys

    PubMed Central

    Mitz, Andrew R.; Tsujimoto, Satoshi; MacLarty, Arthur J.; Wise, Steven P.

    2009-01-01

    Neurophysiological research has explored most of the prefrontal cortex of macaque monkeys, but the relatively inaccessible frontal pole cortex remains unexamined. Here we describe a method for gaining access to the frontal pole cortex with moveable microelectrodes. The key innovation is a direct approach through the frontal air sinus. In addition, the small size of the frontal pole cortex in macaques led to the design of a smaller recording chamber than typically used in behavioral neurophysiology. The method has proven successful in two subjects, with no adverse health consequences. PMID:18977387

  13. Giant cell glioblastoma in the frontal cortex of a dog.

    PubMed

    Uchida, K; Kuroki, K; Priosoeryanto, B P; Kato, K; Yano, Y; Murakami, T; Yamaguchi, R; Tateyama, S

    1995-03-01

    A dark gray mass 3 cm in diameter replacing the right frontal cortex was found in the brain of a 5-year-old male Doberman Pinscher dog at necropsy. Microscopic studies revealed that the mass consisted of a proliferation of pleomorphic tumor cells: large bizarre or plump eosinophilic cells, multinucleated giant cells, and small lymphocytic cells. These neoplastic cells at the margin of the necrotic area had a psuedopalisade arrangement and tended to proliferate around blood vessels. Immunohistochemically, the tumor cells reacted intensely with the antibody for vimentin and moderately with those for S-100 and glial fibrillary acidic protein. This canine tumor is placed in the category of glioblastoma or undifferentiated astrocytoma, which is analogous to human giant cell glioblastoma. PMID:7771064

  14. Neuronal reference frames for social decisions in primate frontal cortex

    PubMed Central

    Chang, Steve W. C.; Gariépy, Jean-Francois; Platt, Michael L.

    2012-01-01

    Social decisions play a crucial role in the success of individuals and the groups they compose. Group members respond vicariously to benefits obtained by others, and impairments in this capacity contribute to neuropsychiatric disorders like autism and sociopathy. We studied how neurons in three frontal cortical areas encode the outcomes of social decisions as monkeys performed a reward-allocation task. Neurons in the orbitofrontal cortex (OFC) predominantly encoded rewards delivered to oneself. Neurons in the anterior cingulate gyrus (ACCg) encoded reward allocations to the other monkey, reward allocations to oneself, or both. Neurons in the anterior cingulate sulcus (ACCs) signaled reward allocations to the other monkey or no one. Within this network of received (OFC) and foregone (ACCs) reward signaling, ACCg emerges as a key nexus for the computation of shared experience and social reward. Individual and species-specific variations in social decision-making might result from the relative activation and influence of these areas. PMID:23263442

  15. Human Medial Frontal Cortex Mediates Unconscious Inhibition of Voluntary Action

    PubMed Central

    Sumner, Petroc; Nachev, Parashkev; Morris, Peter; Peters, Andrew M.; Jackson, Stephen R.; Kennard, Christopher; Husain, Masud

    2007-01-01

    Summary Within the medial frontal cortex, the supplementary eye field (SEF), supplementary motor area (SMA), and pre-SMA have been implicated in the control of voluntary action, especially during motor sequences or tasks involving rapid choices between competing response plans. However, the precise roles of these areas remain controversial. Here, we study two extremely rare patients with microlesions of the SEF and SMA to demonstrate that these areas are critically involved in unconscious and involuntary motor control. We employed masked-prime stimuli that evoked automatic inhibition in healthy people and control patients with lateral premotor or pre-SMA damage. In contrast, our SEF/SMA patients showed a complete reversal of the normal inhibitory effect—ocular or manual—corresponding to the functional subregion lesioned. These findings imply that the SEF and SMA mediate automatic effector-specific suppression of motor plans. This automatic mechanism may contribute to the participation of these areas in the voluntary control of action. PMID:17553420

  16. Facilitated lexical ambiguity processing by transcranial direct current stimulation over the left inferior frontal cortex.

    PubMed

    Ihara, Aya S; Mimura, Takanori; Soshi, Takahiro; Yorifuji, Shiro; Hirata, Masayuki; Goto, Tetsu; Yoshinime, Toshiki; Umehara, Hiroaki; Fujimaki, Norio

    2015-01-01

    Previous studies suggest that the left inferior frontal cortex is involved in the resolution of lexical ambiguities for language comprehension. In this study, we hypothesized that processing of lexical ambiguities is improved when the excitability of the left inferior frontal cortex is enhanced. To test the hypothesis, we conducted an experiment with transcranial direct current stimulation (tDCS). We investigated the effect of anodal tDCS over the left inferior frontal cortex on behavioral indexes for semantic judgment on lexically ambiguous and unambiguous words within a context. Supporting the hypothesis, the RT was shorter in the anodal tDCS session than in the sham session for ambiguous words. The results suggest that controlled semantic retrieval and contextual selection were facilitated by anodal tDCS over the left inferior frontal cortex. PMID:25208744

  17. Spatiotemporal dynamics of excitation in rat insular cortex: intrinsic corticocortical circuit regulates caudal-rostro excitatory propagation from the insular to frontal cortex.

    PubMed

    Fujita, S; Adachi, K; Koshikawa, N; Kobayashi, M

    2010-01-13

    The insular cortex (IC), composing unique anatomical connections, receives multi-modal sensory inputs including visceral, gustatory and somatosensory information from sensory thalamic nuclei. Axonal projections from the limbic structures, which have a profound influence on induction of epileptic activity, also converge onto the IC. However, functional connectivity underlying the physiological and pathological roles characteristic to the IC still remains unclear. The present study sought to elucidate the spatiotemporal dynamics of excitatory propagation and their cellular mechanisms in the IC using optical recording in urethane-anesthetized rats. Repetitive electrical stimulations of the IC at 50 Hz demonstrated characteristic patterns of excitatory propagation depending on the stimulation sites. Stimulation of the granular zone of the IC (GI) and other surrounding cortices such as the motor/primary sensory/secondary sensory cortices evoked round-shaped excitatory propagations, which often extended over the borders of adjacent areas, whereas excitation of the agranular and dysgranular zones in the IC (AI and DI, respectively) spread along the rostrocaudal axis parallel to the rhinal fissure. Stimulation of AI/DI often evoked excitation in the dorsolateral orbital cortex, which exhibited spatially discontinuous topography of excitatory propagation in the IC. Pharmacological manipulations using 6,7-dinitroquinoxaline-2,3(1H,4H)-dione (DNQX), a non-NMDA receptor antagonist, D-2-amino-5-phosphonovaleric acid (D-APV), an NMDA receptor antagonist, and bicuculline methiodide, a GABA(A) receptor antagonist, indicate that excitatory propagation was primarily regulated by non-NMDA and GABA(A) receptors. Microinjection of lidocaine or incision of the supragranular layers of the rostrocaudally middle part of excitatory regions suppressed excitation in the remote regions from the stimulation site, suggesting that the excitatory propagation in the IC is largely mediated by

  18. Plasticity and Functions of the Orbital Frontal Cortex

    ERIC Educational Resources Information Center

    Kolb, Bryan; Pellis, Sergio; Robinson, Terry E.

    2004-01-01

    We compare the effects of psychoactive drugs such as morphine and amphetamine on the synaptic organization of neurons in the orbital frontal (OFC) and medial frontal (mPFC) regions in the rat. Both regions are altered chronically by exposure to intermittent doses of either drug but the effects are area-dependent. For example, whereas morphine…

  19. The differing roles of the frontal cortex in fluency tests

    PubMed Central

    Shallice, Tim; Bozzali, Marco; Cipolotti, Lisa

    2012-01-01

    Fluency tasks have been widely used to tap the voluntary generation of responses. The anatomical correlates of fluency tasks and their sensitivity and specificity have been hotly debated. However, investigation of the cognitive processes involved in voluntary generation of responses and whether generation is supported by a common, general process (e.g. fluid intelligence) or specific cognitive processes underpinned by particular frontal regions has rarely been addressed. This study investigates a range of verbal and non-verbal fluency tasks in patients with unselected focal frontal (n = 47) and posterior (n = 20) lesions. Patients and controls (n = 35) matched for education, age and sex were administered fluency tasks including word (phonemic/semantic), design, gesture and ideational fluency as well as background cognitive tests. Lesions were analysed by standard anterior/posterior and left/right frontal subdivisions as well as a finer-grained frontal localization method. Thus, patients with right and left lateral lesions were compared to patients with superior medial lesions. The results show that all eight fluency tasks are sensitive to frontal lobe damage although only the phonemic word and design fluency tasks were specific to the frontal region. Superior medial patients were the only group to be impaired on all eight fluency tasks, relative to controls, consistent with an energization deficit. The most marked fluency deficits for lateral patients were along material specific lines (i.e. left—phonemic and right—design). Phonemic word fluency that requires greater selection was most severely impaired following left inferior frontal damage. Overall, our results support the notion that frontal functions comprise a set of specialized cognitive processes, supported by distinct frontal regions. PMID:22669082

  20. Association fiber pathways to the frontal cortex from the superior temporal region in the rhesus monkey

    SciTech Connect

    Petrides, M.; Pandya, D.N.

    1988-07-01

    The projections to the frontal cortex that originate from the various areas of the superior temporal region of the rhesus monkey were investigated with the autoradiographic technique. The results demonstrated that the rostral part of the superior temporal gyrus (areas Pro, Ts1, and Ts2) projects to the proisocortical areas of the orbital and medial frontal cortex, as well as to the nearby orbital areas 13, 12, and 11, and to medial areas 9, 10, and 14. These fibers travel to the frontal lobe as part of the uncinate fascicle. The middle part of the superior temporal gyrus (areas Ts3 and paAlt) projects predominantly to the lateral frontal cortex (areas 12, upper 46, and 9) and to the dorsal aspect of the medial frontal lobe (areas 9 and 10). Only a small number of these fibers terminated within the orbitofrontal cortex. The temporofrontal fibers originating from the middle part of the superior temporal gyrus occupy the lower portion of the extreme capsule and lie just dorsal to the fibers of the uncinate fascicle. The posterior part of the superior temporal gyrus projects to the lateral frontal cortex (area 46, dorsal area 8, and the rostralmost part of dorsal area 6). Some of the fibers from the posterior superior temporal gyrus run initially through the extreme capsule and then cross the claustrum as they ascend to enter the external capsule before continuing their course to the frontal lobe. A larger group of fibers curves round the caudalmost Sylvian fissure and travels to the frontal cortex occupying a position just above and medial to the upper branch of the circular sulcus. This latter pathway constitutes a part of the classically described arcuate fasciculus.

  1. Ventral frontal cortex functions and quantified MRI in traumatic brain injury

    PubMed Central

    Fujiwara, Esther; Schwartz, Michael L.; Gao, Fuqiang; Black, Sandra E.; Levine, Brian

    2008-01-01

    Ventral frontal cortex is commonly involved in traumatic brain injury (TBI). The Smell Identification Test (SIT), Object Alternation (OA), and the Iowa Gambling Task (IGT) are associated with this brain region in experimental and neuropsychological research. We examined the relationship of performance on these tests to residual structural brain integrity quantified from MRI in 58 TBI patients, including 18 patients with focal cortical contusions and 40 patients with diffuse injury only. Image analysis yielded regional volumetric measures of gray matter, white matter and cerebrospinal fluid. Multivariate analyses identified distributed patterns of regional volume loss associated with test performance across all three behavioral measures. The tasks were sensitive to effects of TBI. In multivariate analyses, performance in all three tasks was related to gray matter loss including ventral frontal cortex, but the SIT was most sensitive to ventral frontal cortex damage, even in patients without focal lesions. The SIT was further related to temporal lobe and posterior cingulate/retrosplenial volumes. OA and the IGT were associated with superior medial frontal volumes. Complex tasks, such as OA and the IGT, do not consistently localize to a single cortical region. The SIT is associated with the integrity of ventral frontal regions, but it is also affected by distributed damage, although the contribution of undetected olfactory tract or bulb damage could not be ruled out. This study illustrates the scope and limitations of functional localization in human ventral frontal cortex. PMID:17976665

  2. Vulnerability of the Medial Frontal Corticospinal Projection Accompanies Combined Lateral Frontal and Parietal Cortex Injury in Rhesus Monkey

    PubMed Central

    Morecraft, R.J.; Ge, J.; Stilwell-Morecraft, K.S.; McNeal, D.W.; Hynes, S.M.; Pizzimenti, M.A.; Rotella, D.L.; Darling, W.G.

    2014-01-01

    Concurrent damage to the lateral frontal and parietal cortex is common following middle cerebral artery infarction leading to upper extremity paresis, paresthesia and sensory loss. Motor recovery is often poor and the mechanisms that support, or impede this process are unclear. Since the medial wall of the cerebral hemisphere is commonly spared following stroke, we investigated the long-term (6 and 12 month) effects of lateral frontoparietal injury (F2P2 lesion) on the terminal distribution of the corticospinal projection (CSP) from intact, ipsilesional supplementary motor cortex (M2) at spinal levels C5 to T1. Isolated injury to the frontoparietal arm/hand region resulted in a significant loss of contralateral corticospinal boutons from M2 compared to controls. Specifically, reductions occurred in the medial and lateral parts of lamina VII and the dorsal quadrants of lamina IX. There were no statistical differences in the ipsilateral corticospinal projection. Contrary to isolated lateral frontal motor injury (F2 lesion) which results in substantial increases in contralateral M2 labeling in laminae VII and IX (McNeal et al., Journal of Comparative Neurology 518:586-621, 2010), the added effect of adjacent parietal cortex injury to the frontal motor lesion (F2P2 lesion) not only impedes a favorable compensatory neuroplastic response, but results in a substantial loss of M2 CSP terminals. This dramatic reversal of the CSP response suggests a critical trophic role for cortical somatosensory influence on spared ipsilesional frontal corticospinal projections, and that restoration of a favorable compensatory response will require therapeutic intervention. PMID:25349147

  3. Source versus content memory in patients with a unilateral frontal cortex or a temporal lobe excision.

    PubMed

    Thaiss, Laila; Petrides, Michael

    2003-05-01

    It has been suggested previously that patients with a frontal lobe lesion might have a specific impairment in the retrieval of the source of information despite adequate memory for facts. Patients with an anterior temporal excision are known to have impairments in memory for facts and the question arises as to whether they are also impaired in source memory. The present study compared memory for facts and their source in patients with a unilateral frontal cortical or an anterior temporal excision in a situation in which both types of information were encoded explicitly. Patients with a unilateral frontal cortex or a temporal lobe excision watched videos of a game show and were instructed to attend to both the trivia facts and their source (the identity of the speaker or the relative time of presentation). Patients with a frontal cortex excision were not impaired on either fact or source memory. This was true even when a subgroup of patients with an excision involving the dorsolateral frontal cortex was examined. In contrast, patients with a left temporal lobe excision were impaired in both fact and identity source memory and right temporal lobe patients were impaired in identity source memory. All patients performed similarly to normal controls in temporal source memory. The present results are consistent with the view that source information is part of an associative network of information about an episode and that the medial temporal region is critical for both source and content memory. Furthermore, if source information is encoded explicitly, the frontal cortex does not appear to be necessary for its retrieval. Instead, it is proposed that the frontal cortex plays a metacognitive role in memory retrieval. PMID:12690051

  4. Noradrenaline depletion blocks behavioral sparing and alters cortical morphogenesis after neonatal frontal cortex damage in rats.

    PubMed

    Kolb, B; Sutherland, R J

    1992-06-01

    The possibility that cortical noradrenaline (NA) is necessary for sparing of function that occurs after neonatal frontal cortex damage was examined. Spatial localization by rats with frontal cortex damage on postnatal day 7 (P7) was better than that by rats with similar damage sustained as adults. The sparing was abolished in rats depleted of cortical NA by means of neonatal 6-hydroxydopamine (6HDA) administration. The blockade of sparing in the P7 frontal operates was associated with a smaller brain, thinner cortex, and reduced cortical dendritic branching relative to saline-treated P7 frontal operates. NA depletion alone in unoperated rats did not affect spatial learning but did reduce brain size and dendritic branching. Rats with frontal lesions on P4 did not show sparing of spatial localization, and 6HDA administration had no additional behavioral effect. Overall, these data are consistent with the notion that NA has some general function in maintaining some forms of plasticity in posterior cortex. PMID:1607943

  5. Rule learning enhances structural plasticity of long-range axons in frontal cortex.

    PubMed

    Johnson, Carolyn M; Peckler, Hannah; Tai, Lung-Hao; Wilbrecht, Linda

    2016-01-01

    Rules encompass cue-action-outcome associations used to guide decisions and strategies in a specific context. Subregions of the frontal cortex including the orbitofrontal cortex (OFC) and dorsomedial prefrontal cortex (dmPFC) are implicated in rule learning, although changes in structural connectivity underlying rule learning are poorly understood. We imaged OFC axonal projections to dmPFC during training in a multiple choice foraging task and used a reinforcement learning model to quantify explore-exploit strategy use and prediction error magnitude. Here we show that rule training, but not experience of reward alone, enhances OFC bouton plasticity. Baseline bouton density and gains during training correlate with rule exploitation, while bouton loss correlates with exploration and scales with the magnitude of experienced prediction errors. We conclude that rule learning sculpts frontal cortex interconnectivity and adjusts a thermostat for the explore-exploit balance. PMID:26949122

  6. Rule learning enhances structural plasticity of long-range axons in frontal cortex

    PubMed Central

    Johnson, Carolyn M.; Peckler, Hannah; Tai, Lung-Hao; Wilbrecht, Linda

    2016-01-01

    Rules encompass cue-action-outcome associations used to guide decisions and strategies in a specific context. Subregions of the frontal cortex including the orbitofrontal cortex (OFC) and dorsomedial prefrontal cortex (dmPFC) are implicated in rule learning, although changes in structural connectivity underlying rule learning are poorly understood. We imaged OFC axonal projections to dmPFC during training in a multiple choice foraging task and used a reinforcement learning model to quantify explore–exploit strategy use and prediction error magnitude. Here we show that rule training, but not experience of reward alone, enhances OFC bouton plasticity. Baseline bouton density and gains during training correlate with rule exploitation, while bouton loss correlates with exploration and scales with the magnitude of experienced prediction errors. We conclude that rule learning sculpts frontal cortex interconnectivity and adjusts a thermostat for the explore–exploit balance. PMID:26949122

  7. Influence of motivation on control hierarchy in the human frontal cortex.

    PubMed

    Bahlmann, Jörg; Aarts, Esther; D'Esposito, Mark

    2015-02-18

    The frontal cortex mediates cognitive control and motivation to shape human behavior. It is generally observed that medial frontal areas are involved in motivational aspects of behavior, whereas lateral frontal regions are involved in cognitive control. Recent models of cognitive control suggest a rostro-caudal gradient in lateral frontal regions, such that progressively more rostral (anterior) regions process more complex aspects of cognitive control. How motivation influences such a control hierarchy is still under debate. Although some researchers argue that both systems work in parallel, others argue in favor of an interaction between motivation and cognitive control. In the latter case it is yet unclear how motivation would affect the different levels of the control hierarchy. This was investigated in the present functional MRI study applying different levels of cognitive control under different motivational states (low vs high reward anticipation). Three levels of cognitive control were tested by varying rule complexity: stimulus-response mapping (low-level), flexible task updating (mid-level), and sustained cue-task associations (high-level). We found an interaction between levels of cognitive control and motivation in medial and lateral frontal subregions. Specifically, flexible updating (mid-level of control) showed the strongest beneficial effect of reward and only this level exhibited functional coupling between dopamine-rich midbrain regions and the lateral frontal cortex. These findings suggest that motivation differentially affects the levels of a control hierarchy, influencing recruitment of frontal cortical control regions depending on specific task demands. PMID:25698755

  8. Hierarchy of prediction errors for auditory events in human temporal and frontal cortex.

    PubMed

    Dürschmid, Stefan; Edwards, Erik; Reichert, Christoph; Dewar, Callum; Hinrichs, Hermann; Heinze, Hans-Jochen; Kirsch, Heidi E; Dalal, Sarang S; Deouell, Leon Y; Knight, Robert T

    2016-06-14

    Predictive coding theories posit that neural networks learn statistical regularities in the environment for comparison with actual outcomes, signaling a prediction error (PE) when sensory deviation occurs. PE studies in audition have capitalized on low-frequency event-related potentials (LF-ERPs), such as the mismatch negativity. However, local cortical activity is well-indexed by higher-frequency bands [high-γ band (Hγ): 80-150 Hz]. We compared patterns of human Hγ and LF-ERPs in deviance detection using electrocorticographic recordings from subdural electrodes over frontal and temporal cortices. Patients listened to trains of task-irrelevant tones in two conditions differing in the predictability of a deviation from repetitive background stimuli (fully predictable vs. unpredictable deviants). We found deviance-related responses in both frequency bands over lateral temporal and inferior frontal cortex, with an earlier latency for Hγ than for LF-ERPs. Critically, frontal Hγ activity but not LF-ERPs discriminated between fully predictable and unpredictable changes, with frontal cortex sensitive to unpredictable events. The results highlight the role of frontal cortex and Hγ activity in deviance detection and PE generation. PMID:27247381

  9. Stimulus Expectancy Modulates Inferior Frontal Gyrus and Premotor Cortex Activity in Auditory Perception

    ERIC Educational Resources Information Center

    Osnes, Berge; Hugdahl, Kenneth; Hjelmervik, Helene; Specht, Karsten

    2012-01-01

    In studies on auditory speech perception, participants are often asked to perform active tasks, e.g. decide whether the perceived sound is a speech sound or not. However, information about the stimulus, inherent in such tasks, may induce expectations that cause altered activations not only in the auditory cortex, but also in frontal areas such as…

  10. Cognitive Functioning after Medial Frontal Lobe Damage Including the Anterior Cingulate Cortex: A Preliminary Investigation

    ERIC Educational Resources Information Center

    Baird, Amee; Dewar, Bonnie-Kate; Critchley, Hugo; Gilbert, Sam J.; Dolan, Raymond J.; Cipolotti, Lisa

    2006-01-01

    Two patients with medial frontal lobe damage involving the anterior cingulate cortex (ACC) performed a range of cognitive tasks, including tests of executive function and anterior attention. Both patients lesions extended beyond the ACC, therefore caution needs to be exerted in ascribing observed deficits to the ACC alone. Patient performance was…

  11. Protective effects of quercetine on the neuronal injury in frontal cortex after chronic toluene exposure.

    PubMed

    Kanter, Mehmet

    2013-08-01

    The aim of this study was designed to evaluate the possible protective effects of quercetine (QE) on the neuronal injury in the frontal cortex after chronic toluene exposure in rats. The rats were randomly allotted into one of the three experimental groups, namely, groups A (control), B (toluene treated) and C (toluene-treated with QE), where each group contains 10 animals. Control group received 1 ml of normal saline solution, and toluene treatment was performed by the inhalation of 3000 ppm toluene in an 8-h/day and 6-day/week order for 12 weeks. The rats in QE-treated group was given QE (15 mg/kg body weight) once a day intraperitoneally for 12 weeks, starting just after toluene exposure. Tissue samples were obtained for histopathological investigation. To date, no histopathological changes of neurodegeneration in the frontal cortex after chronic toluene exposure in rats by QE treatment have been reported. In this study, the morphology of neurons in the QE treatment group was well protected. Chronic toluene exposure caused severe degenerative changes, shrunken cytoplasm and extensively dark picnotic nuclei in neurons of the frontal cortex. We conclude that QE therapy causes morphologic improvement in neurodegeneration of frontal cortex after chronic toluene exposure in rats. We believe that further preclinical research into the utility of QE may indicate its usefulness as a potential treatment on neurodegeneration after chronic toluene exposure in rats. PMID:22252859

  12. Tritiated imipramine binding sites are decreased in the frontal cortex of suicides

    SciTech Connect

    Stanley, M.; Virgilio, J.; Gershon, S.

    1982-06-18

    Binding characteristics of tritiated imipramine were determined in the frontal cortex of suicides and well-matched controls. Maximal binding was significantly lower in brains from the suicides. This finding is consistent with reports of decreased tritiated imipramine binding in the platelets of patients diagnosed as having a major affective disorder.

  13. Intra- and Interindividual Differences in Lateralized Cognitive Performance and Asymmetrical EEG Activity in the Frontal Cortex

    ERIC Educational Resources Information Center

    Papousek, Ilona; Murhammer, Daniela; Schulter, Gunter

    2011-01-01

    The study shows that changes in relative verbal vs. figural working memory and fluency performance from one session to a second session two to 3 weeks apart covary with spontaneously occurring changes of cortical asymmetry in the lateral frontal and central cortex, measured by electroencephalography (EEG) in resting conditions before the execution…

  14. Functional organization of human intraparietal and frontal cortex for attending, looking, and pointing

    NASA Technical Reports Server (NTRS)

    Astafiev, Serguei V.; Shulman, Gordon L.; Stanley, Christine M.; Snyder, Abraham Z.; Van Essen, David C.; Corbetta, Maurizio

    2003-01-01

    We studied the functional organization of human posterior parietal and frontal cortex using functional magnetic resonance imaging (fMRI) to map preparatory signals for attending, looking, and pointing to a peripheral visual location. The human frontal eye field and two separate regions in the intraparietal sulcus were similarly recruited in all conditions, suggesting an attentional role that generalizes across response effectors. However, the preparation of a pointing movement selectively activated a different group of regions, suggesting a stronger role in motor planning. These regions were lateralized to the left hemisphere, activated by preparation of movements of either hand, and included the inferior and superior parietal lobule, precuneus, and posterior superior temporal sulcus, plus the dorsal premotor and anterior cingulate cortex anteriorly. Surface-based registration of macaque cortical areas onto the map of fMRI responses suggests a relatively good spatial correspondence between human and macaque parietal areas. In contrast, large interspecies differences were noted in the topography of frontal areas.

  15. Memory and executive function impairments after frontal or posterior cortex lesions.

    PubMed

    Daum, Irene; Mayes, Andrew R.

    2000-01-01

    Free recall and recognition, memory for temporal order, spatial memory and prospective memory were assessed in patients with frontal lobe lesions, patients with posterior cortex lesions and control subjects. Both patient groups showed equivalent memory deficits relative to control subjects on a range of free recall and recognition tasks, on memory for temporal order and on a prospective memory task. The patient groups also performed equivalently on the spatial memory task although only patients with frontal lobe lesions were significantly impaired. However, the patients with frontal lobe lesions showed an increased false alarm rate and made more intrusion errors relative not only to the control subjects, but also to the patients with poster or cortex lesions. These memory problems are discussed in relation to deficits in executive function and basic memory processes. PMID:11568428

  16. Cortical Connections of Functional Zones in Posterior Parietal Cortex and Frontal Cortex Motor Regions in New World Monkeys

    PubMed Central

    Stepniewska, Iwona; Kaas, Jon H.

    2011-01-01

    We examined the connections of posterior parietal cortex (PPC) with motor/premotor cortex (M1/PM) and other cortical areas. Electrical stimulation (500 ms trains) delivered to microelectrode sites evoked movements of reach, defense, and grasp, from distinct zones in M1/PM and PPC, in squirrel and owl monkeys. Tracer injections into M1/PM reach, defense, and grasp zones showed dense connections with M1/PM hand/forelimb representations. The densest inputs outside of frontal cortex were from PPC zones. M1 zones were additionally connected with somatosensory hand/forelimb representations in areas 3a, 3b, and 1 and the somatosensory areas of the upper bank of the lateral sulcus (S2/PV). Injections into PPC zones showed primarily local connections and the densest inputs outside of PPC originated from M1/PM zones. The PPC reach zone also received dense inputs from cortex caudal to PPC, which likely relayed visual information. In contrast, the PPC grasp zone was densely connected with the hand/forelimb representations of areas 3a, 3b, 1, and S2/PV. Thus, the dorsal parietal–frontal network involved in reaching was preferentially connected to visual cortex, whereas the more ventral network involved in grasping received somatosensory inputs. Additional weak interlinks between dissimilar zones (e.g., PPC reach and PPC grasp) were apparent and may coordinate actions. PMID:21263034

  17. The Neural System of Postdecision Evaluation in Rostral Frontal Cortex during Problem-solving Tasks

    PubMed Central

    Wan, Xiaohong; Cheng, Kang

    2016-01-01

    Little attention has been paid to the postdecision processing in fMRI studies with task paradigms in which there was no explicit feedback. Although late-onset BOLD responses were previously observed in the lateral frontopolar cortex after the familiar-novel decision on visually presented words, the nature of neural activations that caused the late-onset BOLD responses remained elusive. We here found, in human experts conducting complicated problem-solving tasks in their expertise domain, that the rostral frontal cortex, including the lateral frontopolar cortex, along with the anterior inferior parietal lobule, was activated only during the postdecision period, although there was no feedback. That is, these areas showed late-onset BOLD responses, and fitting of the BOLD responses with different models indicates that they were caused by neural activations that occurred after the decision. However, there was no response after performing a sensory-motor control task, and the magnitude of postdecision activations was correlated with the degree of uncertainty about the preceding decision, which suggests that the postdecision neural activations were associated with the preceding decision procedure. Furthermore, the same set of areas was more strongly activated when the subject explicitly rethought the preceding problem. These results suggest that the rostral frontal cortex, together with anterior inferior parietal lobule, comprises a network for uncertainty monitoring and exploration of alternative resolutions in postdecision evaluation. The present results thus introduce a new aspect of the functional gradient along the rostrocaudal axis in the frontal cortex. PMID:27595134

  18. The Neural System of Postdecision Evaluation in Rostral Frontal Cortex during Problem-solving Tasks.

    PubMed

    Wan, Xiaohong; Cheng, Kang; Tanaka, Keiji

    2016-01-01

    Little attention has been paid to the postdecision processing in fMRI studies with task paradigms in which there was no explicit feedback. Although late-onset BOLD responses were previously observed in the lateral frontopolar cortex after the familiar-novel decision on visually presented words, the nature of neural activations that caused the late-onset BOLD responses remained elusive. We here found, in human experts conducting complicated problem-solving tasks in their expertise domain, that the rostral frontal cortex, including the lateral frontopolar cortex, along with the anterior inferior parietal lobule, was activated only during the postdecision period, although there was no feedback. That is, these areas showed late-onset BOLD responses, and fitting of the BOLD responses with different models indicates that they were caused by neural activations that occurred after the decision. However, there was no response after performing a sensory-motor control task, and the magnitude of postdecision activations was correlated with the degree of uncertainty about the preceding decision, which suggests that the postdecision neural activations were associated with the preceding decision procedure. Furthermore, the same set of areas was more strongly activated when the subject explicitly rethought the preceding problem. These results suggest that the rostral frontal cortex, together with anterior inferior parietal lobule, comprises a network for uncertainty monitoring and exploration of alternative resolutions in postdecision evaluation. The present results thus introduce a new aspect of the functional gradient along the rostrocaudal axis in the frontal cortex. PMID:27595134

  19. The Rostro-Caudal Axis of Frontal Cortex Is Sensitive to the Domain of Stimulus Information

    PubMed Central

    Bahlmann, Jörg; Blumenfeld, Robert S.; D'Esposito, Mark

    2015-01-01

    Evidence suggests that lateral frontal cortex implements cognitive control processing along its rostro-caudal axis, yet other evidence supports a dorsal–ventral functional organization for processes engaged by different stimulus domains (e.g., spatial vs. nonspatial). This functional magnetic resonance imaging study investigated whether separable dorsolateral and ventrolateral rostro-caudal gradients exist in humans, while participants performed tasks requiring cognitive control at 3 levels of abstraction with language or spatial stimuli. Abstraction was manipulated by using 3 different task sets that varied in relational complexity. Relational complexity refers to the process of manipulating the relationship between task components (e.g., to associate a particular cue with a task) and drawing inferences about that relationship. Tasks using different stimulus domains engaged distinct posterior regions, but within the lateral frontal cortex, we found evidence for a single rostro-caudal gradient that was organized according to the level of abstraction and was independent of processing of the stimulus domain. However, a pattern of dorsal/ventral segregation of processing engaged by domain-specific information was evident in each separable frontal region only within the most rostral region recruited by task demands. These results suggest that increasingly abstract information is represented in the frontal cortex along distinct rostro-caudal gradients that also segregate along a dorsal–ventral axis dependent on task demands. PMID:24451658

  20. Different involvement of subregions within dorsal premotor and medial frontal cortex for pro- and antisaccades.

    PubMed

    Cieslik, Edna C; Seidler, Isabelle; Laird, Angela R; Fox, Peter T; Eickhoff, Simon B

    2016-09-01

    The antisaccade task has been widely used to investigate cognitive action control. While the general network for saccadic eye movements is well defined, the exact location of eye fields within the frontal cortex strongly varies between studies. It is unknown whether this inconsistency reflects spatial uncertainty or is the result of different involvement of subregions for specific aspects of eye movement control. The aim of the present study was to examine functional differentiations within the frontal cortex by integrating results from neuroimaging studies analyzing pro- and antisaccade behavior using meta-analyses. The results provide evidence for a differential functional specialization of neighboring oculomotor frontal regions, with lateral frontal eye fields (FEF) and supplementary eye field (SEF) more often involved in prosaccades while medial FEF and anterior midcingulate cortex (aMCC) revealed consistent stronger involvement for antisaccades. This dissociation was furthermore mirrored by functional connectivity analyses showing that the lateral FEF and SEF are embedded in a motor output network, while medial FEF and aMCC are integrated in a multiple demand network. PMID:27211526

  1. Top-Down Control of Human Visual Cortex by Frontal and Parietal Cortex in Anticipatory Visual Spatial Attention

    PubMed Central

    Bressler, Steven L.; Tang, Wei; Sylvester, Chad M.; Shulman, Gordon L.; Corbetta, Maurizio

    2008-01-01

    Advance information about an impending stimulus facilitates its subsequent identification and ensuing behavioral responses. This facilitation is thought to be mediated by top-down control signals from frontal and parietal cortex that modulate sensory cortical activity. Here we show, using Granger Causality measures on blood oxygen-level-dependent time series, that frontal eye field (FEF) and intraparietal sulcus (IPS) activity predicts visual occipital activity prior to an expected visual stimulus. Top-down levels of Granger Causality from FEF and IPS to visual occipital cortex were significantly greater than both bottom-up and mean cortex-wide levels in all individual subjects and the group. In the group and most individual subjects, Granger Causality was significantly greater from FEF to IPS than from IPS to FEF, and significantly greater from both FEF and IPS to intermediate-tier than lower-tier ventral visual areas. Moreover, top-down Granger Causality from right IPS to intermediate-tier areas was predictive of correct behavioral performance. These results suggest that FEF and IPS modulate visual occipital cortex, and FEF modulates IPS, in relation to visual attention. The current approach may prove advantageous for the investigation of interregional directed influences in other human brain functions. PMID:18829963

  2. Orbito-Frontal Cortex Volumes in Panic Disorder

    PubMed Central

    Yildirim, Hanefi; Gurok, M. Gurkan; Akyol, Muammer

    2012-01-01

    Objective Given the association between the pathophysiology of panic disorder and prefrontal cortex function, we aimed to perform a volumetric MRI study in patients with panic disorder and healthy controls focusing on the in vivo neuroanatomy of the OFC. Methods Twenty right-handed patients with panic disorder and 20 right-handed healthy control subjects were studied. The volumes of whole brain, total white and gray matters, and OFC were measured by using T1-weighted coronal MRI images, with 1.5-mm-thick slices, at 1.5T. In addition, for psychological valuation, Hamilton Depression Rating (HDRS) and Panic Agoraphobia Scales (PAS) were administered. Results Unadjusted mean volumes of the whole brain volume, total white and gray matter were not different between the patients and healthy controls while the patient group had significantly smaller left (t=-6.70, p<0.0001) and right (t=-5.86, p<0.0001) OFC volumes compared with healthy controls. Conclusion Our findings indicate an alteration of OFC morphology in the panic disorder and suggest that OFC abnormalities may be involved in the pathophysiology of panic disorder. PMID:23251207

  3. Control of prepotent responses by the superior medial frontal cortex.

    PubMed

    Chen, Chiao-Yun; Muggleton, Neil G; Tzeng, Ovid J L; Hung, Daisy L; Juan, Chi-Hung

    2009-01-15

    The inhibitory control of prepotent action is vital for appropriate behaviour. An example of the importance of such control can be seen in the inhibition of aggressive behavior, deficits in which may have broader consequences for society. Many studies have related lesions or the under-development of the prefrontal cortex to inefficiency of inhibitory control. Here we used transcranial magnetic stimulation and a stop-signal task, which occasionally requires the inhibition of a prepotent motor response, to investigate the role of pre-supplementary motor area (Pre-SMA) in inhibitory control. While no effects were seen on the ability to generate responses, TMS delivered over the Pre-SMA disrupted the ability to respond to a stop signal. These results are the first to establish a casual link between Pre-SMA and inhibitory control in normal subjects. The understanding of the underlying mechanisms of inhibitory control may lead to clearer understanding of the neural basis of inappropriate behaviour. PMID:18852054

  4. The frontal cortex and the criminal justice system.

    PubMed Central

    Sapolsky, Robert M

    2004-01-01

    In recent decades, the general trend in the criminal justice system in the USA has been to narrow the range of insanity defences available, with an increasing dependence solely on the M'Naghten rule. This states that innocence by reason of insanity requires that the perpetrator could not understand the nature of their criminal act, or did not know that the act was wrong, by reason of a mental illness. In this essay, I question the appropriateness of this, in light of contemporary neuroscience. Specifically, I focus on the role of the prefrontal cortex (PFC) in cognition, emotional regulation, control of impulsive behaviour and moral reasoning. I review the consequences of PFC damage on these endpoints, the capacity for factors such as alcohol and stress to transiently impair PFC function, and the remarkably late development of the PFC (in which full myelination may not occur until early adulthood). I also consider how individual variation in PFC function and anatomy, within the normative range, covaries with some of these endpoints. This literature is reviewed because of its relevance to issues of criminal insanity; specifically, damage can produce an individual capable of differentiating right from wrong but who, nonetheless, is organically incapable of appropriately regulating their behaviour. PMID:15590619

  5. Frontal and motor cortex contributions to response inhibition: evidence from electrocorticography.

    PubMed

    Fonken, Yvonne M; Rieger, Jochem W; Tzvi, Elinor; Crone, Nathan E; Chang, Edward; Parvizi, Josef; Knight, Robert T; Krämer, Ulrike M

    2016-04-01

    Changes in the environment require rapid modification or inhibition of ongoing behavior. We used the stop-signal paradigm and intracranial recordings to investigate response preparation, inhibition, and monitoring of task-relevant information. Electrocorticographic data were recorded in eight patients with electrodes covering frontal, temporal, and parietal cortex, and time-frequency analysis was used to examine power differences in the beta (13-30 Hz) and high-gamma bands (60-180 Hz). Over motor cortex, beta power decreased, and high-gamma power increased during motor preparation for both go trials (Go) and unsuccessful stops (US). For successful stops (SS), beta increased, and high-gamma was reduced, indexing the cancellation of the prepared response. In the middle frontal gyrus (MFG), stop signals elicited a transient high-gamma increase. The MFG response occurred before the estimated stop-signal reaction time but did not distinguish between SS and US trials, likely signaling attention to the salient stop stimulus. A postresponse high-gamma increase in MFG was stronger for US compared with SS and absent in Go, supporting a role in behavior monitoring. These results provide evidence for differential contributions of frontal subregions to response inhibition, including motor preparation and inhibitory control in motor cortex and cognitive control and action evaluation in lateral prefrontal cortex. PMID:26864760

  6. Dyslexic children lack word selectivity gradients in occipito-temporal and inferior frontal cortex

    PubMed Central

    Olulade, O.A.; Flowers, D.L.; Napoliello, E.M.; Eden, G.F.

    2015-01-01

    fMRI studies using a region-of-interest approach have revealed that the ventral portion of the left occipito-temporal cortex, which is specialized for orthographic processing of visually presented words (and includes the so-called “visual word form area”, VWFA), is characterized by a posterior-to-anterior gradient of increasing selectivity for words in typically reading adults, adolescents, and children (e.g. Brem et al., 2006, 2009). Similarly, the left inferior frontal cortex (IFC) has been shown to exhibit a medial-to-lateral gradient of print selectivity in typically reading adults (Vinckier et al., 2007). Functional brain imaging studies of dyslexia have reported relative underactivity in left hemisphere occipito-temporal and inferior frontal regions using whole-brain analyses during word processing tasks. Hence, the question arises whether gradient sensitivities in these regions are altered in dyslexia. Indeed, a region-of-interest analysis revealed the gradient-specific functional specialization in the occipito-temporal cortex to be disrupted in dyslexic children (van der Mark et al., 2009). Building on these studies, we here (1) investigate if a word-selective gradient exists in the inferior frontal cortex in addition to the occipito-temporal cortex in normally reading children, (2) compare typically reading with dyslexic children, and (3) examine functional connections between these regions in both groups. We replicated the previously reported anterior-to-posterior gradient of increasing selectivity for words in the left occipito-temporal cortex in typically reading children, and its absence in the dyslexic children. Our novel finding is the detection of a pattern of increasing selectivity for words along the medial-to-lateral axis of the left inferior frontal cortex in typically reading children and evidence of functional connectivity between the most lateral aspect of this area and the anterior aspects of the occipito-temporal cortex. We report

  7. Dyslexic children lack word selectivity gradients in occipito-temporal and inferior frontal cortex.

    PubMed

    Olulade, O A; Flowers, D L; Napoliello, E M; Eden, G F

    2015-01-01

    fMRI studies using a region-of-interest approach have revealed that the ventral portion of the left occipito-temporal cortex, which is specialized for orthographic processing of visually presented words (and includes the so-called "visual word form area", VWFA), is characterized by a posterior-to-anterior gradient of increasing selectivity for words in typically reading adults, adolescents, and children (e.g. Brem et al., 2006, 2009). Similarly, the left inferior frontal cortex (IFC) has been shown to exhibit a medial-to-lateral gradient of print selectivity in typically reading adults (Vinckier et al., 2007). Functional brain imaging studies of dyslexia have reported relative underactivity in left hemisphere occipito-temporal and inferior frontal regions using whole-brain analyses during word processing tasks. Hence, the question arises whether gradient sensitivities in these regions are altered in dyslexia. Indeed, a region-of-interest analysis revealed the gradient-specific functional specialization in the occipito-temporal cortex to be disrupted in dyslexic children (van der Mark et al., 2009). Building on these studies, we here (1) investigate if a word-selective gradient exists in the inferior frontal cortex in addition to the occipito-temporal cortex in normally reading children, (2) compare typically reading with dyslexic children, and (3) examine functional connections between these regions in both groups. We replicated the previously reported anterior-to-posterior gradient of increasing selectivity for words in the left occipito-temporal cortex in typically reading children, and its absence in the dyslexic children. Our novel finding is the detection of a pattern of increasing selectivity for words along the medial-to-lateral axis of the left inferior frontal cortex in typically reading children and evidence of functional connectivity between the most lateral aspect of this area and the anterior aspects of the occipito-temporal cortex. We report absence

  8. Prenatal exposure to moderate levels of ethanol alters social behavior in adult rats: Relationship to structural plasticity and immediate early gene expression in frontal cortex

    PubMed Central

    Hamilton, Derek A.; Akers, Katherine G.; Rice, James P.; Johnson, Travis E.; Candelaria-Cook, Felicha T.; Maes, Levi I.; Rosenberg, Martina; Valenzuela, C. Fernando; Savage, Daniel D.

    2009-01-01

    The goals of the present study were to characterize the effects of prenatal exposure to moderate levels of ethanol on adult social behavior, and to evaluate fetal-ethanol-related effects on dendritic morphology, structural plasticity and activity-related immediate early gene (IEG) expression in the agranular insular (AID) and prelimbic (Cg3) regions of frontal cortex. Baseline fetal-ethanol-related alterations in social behavior were limited to reductions in social investigation in males. Repeated experience with novel cage-mates resulted in comparable increases in wrestling and social investigation among saccharin- and ethanol-exposed females, whereas social behavioral effects among males were more evident in ethanol-exposed animals. Male ethanol-exposed rats also displayed profound increases in wrestling when social interaction was motivated by 24 hours of isolation. Baseline decreases in dendritic length and spine density in AID were observed in ethanol-exposed rats that were always housed with the same cage-mate. Modest experience-related decreases in dendritic length and spine density in AID were observed in saccharin-exposed rats housed with various cage-mates. In contrast, fetal-ethanol-exposed rats displayed experience-related increases in dendritic length in AID, and no experience-related changes in spine density. The only effect observed in Cg3 was a baseline increase in basilar dendritic length among male ethanol-exposed rats. Robust increases in activity-related IEG expression in AID (c-fos and Arc) and Cg3 (c-fos) were observed following social interaction in saccharin-exposed rats, however, activity-related increases in IEG expression were not observed in fetal-ethanol-exposed rats in either region. The results indicate that deficits in social behavior are among the long-lasting behavioral consequences of moderate ethanol exposure during brain development, and implicate AID, and to a lesser degree Cg3, in fetal-ethanol-related social behavior

  9. Top-down-directed synchrony from medial frontal cortex to nucleus accumbens during reward anticipation.

    PubMed

    Cohen, Michael X; Bour, Lo; Mantione, Mariska; Figee, Martijn; Vink, Matthijs; Tijssen, Marina A J; van Rootselaar, Anne-Fleur; van den Munckhof, Pepijn; Schuurman, P Richard; Denys, Damiaan

    2012-01-01

    The nucleus accumbens and medial frontal cortex (MFC) are part of a loop involved in modulating behavior according to anticipated rewards. However, the precise temporal landscape of their electrophysiological interactions in humans remains unknown because it is not possible to record neural activity from the nucleus accumbens using noninvasive techniques. We recorded electrophysiological activity simultaneously from the nucleus accumbens and cortex (via surface EEG) in humans who had electrodes implanted as part of deep-brain-stimulation treatment for obsessive-compulsive disorder. Patients performed a simple reward motivation task previously shown to activate the ventral striatum. Spectral Granger causality analyses were applied to dissociate "top-down" (cortex → nucleus accumbens)- from "bottom-up" (nucleus accumbens → cortex)-directed synchronization (functional connectivity). "Top-down"-directed synchrony from cortex to nucleus accumbens was maximal over medial frontal sites and was significantly stronger when rewards were anticipated. These findings provide direct electrophysiological evidence for a role of the MFC in modulating nucleus accumbens reward-related processing and may be relevant to understanding the mechanisms of deep-brain stimulation and its beneficial effects on psychiatric conditions. PMID:21547982

  10. Enhancement of 18F-Fluorodeoxyglucose Metabolism in Rat Brain Frontal Cortex Using a β3 Adrenoceptor Agonist

    PubMed Central

    Mirbolooki, M. Reza; Schade, Kimberly N.; Constantinescu, Cristian C.; Pan, Min-Liang; Mukherjee, Jogeshwar

    2014-01-01

    We report the use of β3-adrenergic receptor mediated activation of rat brain frontal cortex using mirabegron (a selective β3-adrenoceptor agonist), measured by 18F-FDG PET/CT. Another β3-agonis t, CL 316,243, did not have this effect due to impermeability through the blood brain barrier (BBB), while atomoxetine, a norepinephrine transporter blocker, did increase 18F-FDG uptake in the frontal cortex. Mirabegron exhibited a dose-dependent increase in frontal cortex 18F-FDG uptake. These findings suggest a possible use of selective β3-adrenoceptor agonists in reversing regional glucose hypometabolism in the brain. PMID:25347981

  11. Reduced high affinity cholecystokinin binding in hippocampus and frontal cortex of schizophrenic patients

    SciTech Connect

    Farmery, S.M.; Owen, F.; Poulter, M.; Crow, T.J.

    1985-02-04

    Cholecystokinin (CCK) binding sites were assessed in post-mortem brain membrane preparations from controls and schizophrenic patients. /sup 125/ I-BH CCK/sub 33/ specific binding was reduced by 40% (p < 0.02) in the hippocampus and by 20% (p < 0.01) in the frontal cortex of schizophrenic patients compared with controls. There were no differences in /sup 125/I-BH CCK/sub 33/ binding between the two groups in the amygdala, temporal cortex or caudate nucleus. 20 references, 1 figure, 2 tables.

  12. Direction- and distance-dependent interareal connectivity of pyramidal cell subpopulations in the rat frontal cortex

    PubMed Central

    Ueta, Yoshifumi; Hirai, Yasuharu; Otsuka, Takeshi; Kawaguchi, Yasuo

    2013-01-01

    The frontal cortex plays an important role in the initiation and execution of movements via widespread projections to various cortical and subcortical areas. Layer 2/3 (L2/3) pyramidal cells in the frontal cortex send axons mainly to other ipsilateral/contralateral cortical areas. Subpopulations of layer 5 (L5) pyramidal cells that selectively project to the pontine nuclei or to the contralateral cortex [commissural (COM) cells] also target diverse and sometimes overlapping ipsilateral cortical areas. However, little is known about target area-dependent participation in ipsilateral corticocortical (iCC) connections by subclasses of L2/3 and L5 projection neurons. To better understand the functional hierarchy between cortical areas, we compared iCC connectivity between the secondary motor cortex (M2) and adjacent areas, such as the orbitofrontal and primary motor cortices, and distant non-frontal areas, such as the perirhinal and posterior parietal cortices. We particularly assessed the laminar distribution of iCC cells and fibers, and identified the subtypes of pyramidal cells participating in those projections. For connections between M2 and frontal areas, L2/3 and L5 cells in both areas contributed to reciprocal projections, which can be viewed as “bottom-up” or “top-down” on the basis of their differential targeting of cortical lamina. In connections between M2 and non-frontal areas, neurons participating in bottom-up and top-down projections were segregated into the different layers: bottom-up projections arose primarily from L2/3 cells, while top-down projections were dominated by L5 COM cells. These findings suggest that selective participation in iCC connections by pyramidal cell subtypes lead to directional connectivity between M2 and other cortical areas. Based on these findings, we propose a provisional unified framework of interareal hierarchy within the frontal cortex, and discuss the interaction of local circuits with long-range interareal

  13. GABAA receptor complex function in frontal cortex membranes from control and neurological patients.

    PubMed

    Lloyd, G K; Lowenthal, A; Javoy-Agid, F; Constantidinis, J

    1991-05-01

    The functional integrity of the GABAA receptor-benzodiazepine (BZ) recognition site-Cl- ionophore complex was assessed by means of [35S]TBPS (t-butylbicyclophosphorothionate) binding to frontal cortex membranes prepared from frozen postmortem brain tissue taken from control (n = 4), Alzheimer (n = 7), Parkinson (n = 3) and Huntington's chorea (n = 2) patients. Specific [35S]TBPS binding was similar in control, Parkinson's disease and Huntington's chorea brains, but was significantly reduced (78% control, P less than 0.01) in frontal cortex membranes from Alzheimer's patients. The linkage between the BZ recognition sites and the GABAA receptor-linked Cl- ionophore was functionally intact in these membranes as BZ site agonists (zolpidem, alpidem, flunitrazepam and clonazepam) enhanced [35S]TBPS binding under the conditions used (well-washed membranes in the presence of 1.0 M NaCl). Zolpidem (BZ1 selective) exhibited a biphasic enhancement in control membranes whereas the other compounds induced a bell-shaped concentration-response curve. The enhancement of [35S]TBPS binding by alpidem, flunitrazepam and clonazepam was greater in frontal cortex membranes from Alzheimer's patients than in controls whereas it tended to be reduced in membranes from the brains of Huntington's chorea patients. These studies demonstrate the functional integrity of the GABAA receptor macromolecular complex and also the usefulness of [35S]TBPS binding in the study of human postmortem tissue. PMID:1654259

  14. Hypoactivation in right inferior frontal cortex is specifically associated with motor response inhibition in adult ADHD

    PubMed Central

    Morein-Zamir, Sharon; Dodds, Chris; van Hartevelt, Tim J; Schwarzkopf, Wolfgang; Sahakian, Barbara; Müller, Ulrich; Robbins, Trevor

    2014-01-01

    Adult ADHD has been linked to impaired motor response inhibition and reduced associated activation in the right inferior frontal cortex (IFC). However, it is unclear whether abnormal inferior frontal activation in adult ADHD is specifically related to a response inhibition deficit or reflects a more general deficit in attentional processing. Using functional magnetic resonance imaging, we tested a group of 19 ADHD patients with no comorbidities and a group of 19 healthy control volunteers on a modified go/no-go task that has been shown previously to distinguish between cortical responses related to response inhibition and attentional shifting. Relative to the healthy controls, ADHD patients showed increased commission errors and reduced activation in inferior frontal cortex during response inhibition. Crucially, this reduced activation was observed when controlling for attentional processing, suggesting that hypoactivation in right IFC in ADHD is specifically related to impaired response inhibition. The results are consistent with the notion of a selective neurocognitive deficit in response inhibition in adult ADHD associated with abnormal functional activation in the prefrontal cortex, whilst ruling out likely group differences in attentional orienting, arousal and motivation. Hum Brain Mapp 35:5141–5152, 2014. PMID:24819224

  15. A direct GABAergic output from the basal ganglia to frontal cortex

    PubMed Central

    Saunders, Arpiar; Oldenburg, Ian A.; Berezovskii, Vladimir K.; Johnson, Caroline A.; Kingery, Nathan D.; Elliott, Hunter L.; Xie, Tiao; Gerfen, Charles R.; Sabatini, Bernardo L.

    2014-01-01

    The basal ganglia (BG) are phylogenetically conserved subcortical nuclei necessary for coordinated motor action and reward learning1. Current models postulate that the BG modulate cerebral cortex indirectly via an inhibitory output to thalamus, bidirectionally controlled by the BG via direct (dSPNs) and indirect (iSPNs) pathway striatal projection neurons2–4. The BG thalamic output sculpts cortical activity by interacting with signals from sensory and motor systems5. Here we describe a direct projection from the globus pallidus externus (GP), a central nucleus of the BG, to frontal regions of the cerebral cortex (FC). Two cell types make up the GP-FC projection, distinguished by their electrophysiological properties, cortical projections and expression of choline acetyltransferase (ChAT), a synthetic enzyme for the neurotransmitter acetylcholine (ACh). Despite these differences, ChAT+ cells, which have been historically identified as an extension of the nucleus basalis (NB), as well as ChAT− cells, release the inhibitory neurotransmitter GABA (γ-aminobutyric acid) and are inhibited by iSPNs and dSPNs of dorsal striatum. Thus GP-FC cells comprise a direct GABAergic/cholinergic projection under the control of striatum that activates frontal cortex in vivo. Furthermore, iSPN inhibition of GP-FC cells is sensitive to dopamine 2 receptor signaling, revealing a pathway by which drugs that target dopamine receptors for the treatment of neuropsychiatric disorders can act in the BG to modulate frontal cortices. PMID:25739505

  16. A direct GABAergic output from the basal ganglia to frontal cortex.

    PubMed

    Saunders, Arpiar; Oldenburg, Ian A; Berezovskii, Vladimir K; Johnson, Caroline A; Kingery, Nathan D; Elliott, Hunter L; Xie, Tiao; Gerfen, Charles R; Sabatini, Bernardo L

    2015-05-01

    The basal ganglia are phylogenetically conserved subcortical nuclei necessary for coordinated motor action and reward learning. Current models postulate that the basal ganglia modulate cerebral cortex indirectly via an inhibitory output to thalamus, bidirectionally controlled by direct- and indirect-pathway striatal projection neurons (dSPNs and iSPNs, respectively). The basal ganglia thalamic output sculpts cortical activity by interacting with signals from sensory and motor systems. Here we describe a direct projection from the globus pallidus externus (GP), a central nucleus of the basal ganglia, to frontal regions of the cerebral cortex (FC). Two cell types make up the GP-FC projection, distinguished by their electrophysiological properties, cortical projections and expression of choline acetyltransferase (ChAT), a synthetic enzyme for the neurotransmitter acetylcholine (ACh). Despite these differences, ChAT(+) cells, which have been historically identified as an extension of the nucleus basalis, as well as ChAT(-) cells, release the inhibitory neurotransmitter GABA (γ-aminobutyric acid) and are inhibited by iSPNs and dSPNs of dorsal striatum. Thus, GP-FC cells comprise a direct GABAergic/cholinergic projection under the control of striatum that activates frontal cortex in vivo. Furthermore, iSPN inhibition of GP-FC cells is sensitive to dopamine 2 receptor signalling, revealing a pathway by which drugs that target dopamine receptors for the treatment of neuropsychiatric disorders can act in the basal ganglia to modulate frontal cortices. PMID:25739505

  17. Septum and medial frontal cortex contribution to spatial problem-solving.

    PubMed

    Poucet, B; Herrmann, T

    1990-03-26

    An attempt was made to contrast the effects of lesions to the medial frontal cortex and septum in two spatial tasks. In the fixed-goal (FG) task, the food was located on the same table throughout testing, and the start table was randomly varied from day to day. In the variable-goal (VG) task, the start table remained constant but the food was randomly distributed on one or the other of the two remaining tables. In both tasks, normal animals performed better than frontal and septal rats whose performance, however, improved over days in the FG, but not in the VG, task. In both tasks, significant improvement within days was found in medial frontal animals, but not in septal animals. Additional analyses revealed that septal animals had a general pattern of disrupted exploration and a tendency to use a response strategy (i.e. to repeat the same response both within and between days) which decreased over days in the FG task. In contrast, medial frontal animals did not demonstrate disrupted exploration nor any response tendency. It is concluded that both septal and medial frontal cortical damage produce a common spatial working memory impairment. However, there is some evidence to suggest that this common memory impairment could result from disruption of distinct mechanisms in septal and frontal animals. It is proposed that medial frontal lesions could affect some specific mechanism related either to attentional processes or to the ability to anticipate future events, whereas septal damage would interfere with the building of comprehensive and flexible spatial memories. PMID:2340101

  18. Attentional Control of Task and Response in Lateral and Medial Frontal Cortex: Brain Activity and Reaction Time Distributions

    ERIC Educational Resources Information Center

    Aarts, Esther; Roelofs, Ardi; van Turennout, Miranda

    2009-01-01

    It is unclear whether task conflict is reflected in the anterior cingulate cortex (ACC) or in more dorsal regions of the medial frontal cortex (MFC). When participants switch between tasks involving incongruent, congruent, and neutral stimuli, it is possible to examine both response conflict (incongruent vs. congruent) and task conflict (congruent…

  19. Co-Activation-Based Parcellation of the Lateral Prefrontal Cortex Delineates the Inferior Frontal Junction Area.

    PubMed

    Muhle-Karbe, Paul S; Derrfuss, Jan; Lynn, Margaret T; Neubert, Franz X; Fox, Peter T; Brass, Marcel; Eickhoff, Simon B

    2016-05-01

    The inferior frontal junction (IFJ) area, a small region in the posterior lateral prefrontal cortex (LPFC), has received increasing interest in recent years due to its central involvement in the control of action, attention, and memory. Yet, both its function and anatomy remain controversial. Here, we employed a meta-analytic parcellation of the left LPFC to show that the IFJ can be isolated based on its specific functional connections. A seed region, oriented along the left inferior frontal sulcus (IFS), was subdivided via cluster analyses of voxel-wise whole-brain co-activation patterns. The ensuing clusters were characterized by their unique connections, the functional profiles of associated experiments, and an independent topic mapping approach. A cluster at the posterior end of the IFS matched previous descriptions of the IFJ in location and extent and could be distinguished from a more caudal cluster involved in motor control, a more ventral cluster involved in linguistic processing, and 3 more rostral clusters involved in other aspects of cognitive control. Overall, our findings highlight that the IFJ constitutes a core functional unit within the frontal lobe and delineate its borders. Implications for the IFJ's role in human cognition and the organizational principles of the frontal lobe are discussed. PMID:25899707

  20. Stimulus expectancy modulates inferior frontal gyrus and premotor cortex activity in auditory perception.

    PubMed

    Osnes, Berge; Hugdahl, Kenneth; Hjelmervik, Helene; Specht, Karsten

    2012-04-01

    In studies on auditory speech perception, participants are often asked to perform active tasks, e.g. decide whether the perceived sound is a speech sound or not. However, information about the stimulus, inherent in such tasks, may induce expectations that cause altered activations not only in the auditory cortex, but also in frontal areas such as inferior frontal gyrus (IFG) and motor cortices, even in the absence of an explicit task. To investigate this, we applied spectral mixes of a flute sound and either vowels or specific music instrument sounds (e.g. trumpet) in an fMRI study, in combination with three different instructions. The instructions either revealed no information about stimulus features, or explicit information about either the music instrument or the vowel features. The results demonstrated that, besides an involvement of posterior temporal areas, stimulus expectancy modulated in particular a network comprising IFG and premotor cortices during this passive listening task. PMID:22377261

  1. Auditory sequence processing reveals evolutionarily conserved regions of frontal cortex in macaques and humans.

    PubMed

    Wilson, Benjamin; Kikuchi, Yukiko; Sun, Li; Hunter, David; Dick, Frederic; Smith, Kenny; Thiele, Alexander; Griffiths, Timothy D; Marslen-Wilson, William D; Petkov, Christopher I

    2015-01-01

    An evolutionary account of human language as a neurobiological system must distinguish between human-unique neurocognitive processes supporting language and evolutionarily conserved, domain-general processes that can be traced back to our primate ancestors. Neuroimaging studies across species may determine whether candidate neural processes are supported by homologous, functionally conserved brain areas or by different neurobiological substrates. Here we use functional magnetic resonance imaging in Rhesus macaques and humans to examine the brain regions involved in processing the ordering relationships between auditory nonsense words in rule-based sequences. We find that key regions in the human ventral frontal and opercular cortex have functional counterparts in the monkey brain. These regions are also known to be associated with initial stages of human syntactic processing. This study raises the possibility that certain ventral frontal neural systems, which play a significant role in language function in modern humans, originally evolved to support domain-general abilities involved in sequence processing. PMID:26573340

  2. Auditory sequence processing reveals evolutionarily conserved regions of frontal cortex in macaques and humans

    PubMed Central

    Wilson, Benjamin; Kikuchi, Yukiko; Sun, Li; Hunter, David; Dick, Frederic; Smith, Kenny; Thiele, Alexander; Griffiths, Timothy D.; Marslen-Wilson, William D.; Petkov, Christopher I.

    2015-01-01

    An evolutionary account of human language as a neurobiological system must distinguish between human-unique neurocognitive processes supporting language and evolutionarily conserved, domain-general processes that can be traced back to our primate ancestors. Neuroimaging studies across species may determine whether candidate neural processes are supported by homologous, functionally conserved brain areas or by different neurobiological substrates. Here we use functional magnetic resonance imaging in Rhesus macaques and humans to examine the brain regions involved in processing the ordering relationships between auditory nonsense words in rule-based sequences. We find that key regions in the human ventral frontal and opercular cortex have functional counterparts in the monkey brain. These regions are also known to be associated with initial stages of human syntactic processing. This study raises the possibility that certain ventral frontal neural systems, which play a significant role in language function in modern humans, originally evolved to support domain-general abilities involved in sequence processing. PMID:26573340

  3. An Additional Motor-Related Field in the Lateral Frontal Cortex of Squirrel Monkeys

    PubMed Central

    Duric, Vanja; Barbay, Scott; Frost, Shawn B.; Stylianou, Antonis; Nudo, Randolph J.

    2008-01-01

    Our earlier efforts to document the cortical connections of the ventral premotor cortex (PMv) revealed dense connections with a field rostral and lateral to PMv, an area we called the frontal rostral field (FR). Here, we present data collected in FR using electrophysiological and anatomical methods. Results show that FR contains an isolated motor representation of the forelimb that can be differentiated from PMv based on current thresholds and latencies to evoke electromyographic activity using intracortical microstimulation techniques. In addition, FR has a different pattern of cortical connections compared with PMv. Together, these data support that FR is an additional, previously undescribed motor-related area in squirrel monkeys. PMID:18424778

  4. Neonatal Leptin Deficiency Reduces Frontal Cortex Volumes and Programs Adult Hyperactivity in Mice

    PubMed Central

    Dexter, Benjamin C; Rahmouni, Kamal; Cushman, Taylor; Hermann, Gregory M; Ni, Charles; Nopoulos, Peg C; Thedens, Daniel L; Roghair, Robert D

    2014-01-01

    Intrauterine growth restriction and premature delivery decrease circulating levels of the neurotrophic hormone leptin and increase the risk of adult psychiatric disease. In mouse models, neonatal leptin replacement normalizes brain growth and improves the neurodevelopmental outcomes of growth restricted mice, but leptin supplementation of well-grown mice decreases adult locomotor activity. We hypothesized isolated neonatal leptin deficiency is sufficient to reduce adult brain volumes and program behavioral outcomes, including hyperactivity. C57Bl/6 pups were randomized to daily injections of saline or PEG-leptin antagonist (LX, 12.5 mg/kg) from postnatal day 4 to 14. After 4 months, fear conditioning and open field testing were performed followed by carotid radiotelemetry for the measurement of baseline activity and blood pressure. Neonatal LX did not significantly increase cue-based fear or blood pressure, but increased adult locomotor activity during assessment in both the open field (beam breaks: control 930±40, LX 1099±42, P<0.01) and the home cage (radiotelemetry counts: control 4.5±0.3, LX 5.6±0.3, P=0.02). Follow-up MRI revealed significant reductions in adult frontal cortex volumes following neonatal LX administration (control 45.1±0.4 mm3, LX 43.8±0.4 mm3, P=0.04). This was associated with a significant increase in cerebral cortex leptin receptor mRNA expression. In conclusion, isolated neonatal leptin deficiency increases cerebral cortex leptin receptor expression and reduces frontal cortex volumes in association with increased adult locomotor activity. We speculate neonatal leptin deficiency may contribute to the adverse neurodevelopmental outcomes associated with perinatal growth restriction, and postnatal leptin therapy may be protective. PMID:24472638

  5. [Interaction between neurons of the frontal cortex and hippocampus during the realization of choice of food reinforcement quality in cats].

    PubMed

    Merzhanova, G Kh; Dolbakian, E E; Khokhlova, V N

    2003-01-01

    Six cats were subjected to the procedure of appetitive instrumental conditioning (with light as a conditioned stimuls) by the method of the "active choice" of reinforcement quality. Short-delay conditioned bar-press responses were rewarded with bread-meat mixture, and the delayed responses were reinforced by meat. The animals differed in behavior strategy: four animals preferred the bar-pressing with a long delay (the so-called "self-control" group), and two cats preferred the bar-pressing with a short delay (the so-called "impulsive" group). Multiunit activity in the frontal cortex and hippocampus (CA3) was recorded via chronically implanted nichrome wire semimicroelectrodes. An interaction between the neighboring neurons in the frontal cortex and hippocampus (within local neural networks) and between the neurons of the frontal cortex and hippocampus (distributed neural networks in frontal-hippocampal and hippocampal-frontal directions) was evaluated by means of statistical crosscorrelation analysis of spike trains. Crosscorrelations between neuronal spike trains in the delay range of 0-100 ms were explored. It was shown that the number of crosscorrelations between the neuronal discharges both in the local and distributed networks was significantly higher in the "self-control" cats. It was suggested that the local and distributed neural networks of the frontal cortex and hippocampus are involved in the system of brain structures which determine the behavioral strategy of animals in the "self-control" group. PMID:12889201

  6. Microglia recapitulate a hematopoietic master regulator network in the aging human frontal cortex

    PubMed Central

    Wehrspaun, Claudia C.; Haerty, Wilfried; Ponting, Chris P.

    2015-01-01

    Microglia form the immune system of the brain. Previous studies in cell cultures and animal models suggest altered activation states and cellular senescence in the aged brain. Instead, we analyzed 3 transcriptome data sets from the postmortem frontal cortex of 381 control individuals to show that microglia gene markers assemble into a transcriptional module in a gene coexpression network. These markers predominantly represented M1 and M1/M2b activation phenotypes. Expression of genes in this module generally declines over the adult life span. This decrease was more pronounced in microglia surface receptors for microglia and/or neuron crosstalk than in markers for activation state phenotypes. In addition to these receptors for exogenous signals, microglia are controlled by brain-expressed regulatory factors. We identified a subnetwork of transcription factors, including RUNX1, IRF8, PU.1, and TAL1, which are master regulators (MRs) for the age-dependent microglia module. The causal contributions of these MRs on the microglia module were verified using publicly available ChIP-Seq data. Interactions of these key MRs were preserved in a protein-protein interaction network. Importantly, these MRs appear to be essential for regulating microglia homeostasis in the adult human frontal cortex in addition to their crucial roles in hematopoiesis and myeloid cell-fate decisions during embryogenesis. PMID:26002684

  7. Evolution of increased glia–neuron ratios in the human frontal cortex

    PubMed Central

    Sherwood, Chet C.; Stimpson, Cheryl D.; Raghanti, Mary Ann; Wildman, Derek E.; Uddin, Monica; Grossman, Lawrence I.; Goodman, Morris; Redmond, John C.; Bonar, Christopher J.; Erwin, Joseph M.; Hof, Patrick R.

    2006-01-01

    Evidence from comparative studies of gene expression and evolution suggest that human neocortical neurons may be characterized by unusually high levels of energy metabolism. The current study examined whether there is a disproportionate increase in glial cell density in the human frontal cortex in comparison with other anthropoid primate species (New World monkeys, Old World monkeys, and hominoids) to support greater metabolic demands. Among 18 species of anthropoids, humans displayed the greatest departure from allometric scaling expectations for the density of glia relative to neurons in layer II/III of dorsolateral prefrontal cortex (area 9L). However, the human glia–neuron ratio in this prefrontal region did not differ significantly from allometric predictions based on brain size. Further analyses of glia–neuron ratios across frontal areas 4, 9L, 32, and 44 in a sample of humans, chimpanzees, and macaque monkeys showed that regions involved in specialized human cognitive functions, such as “theory of mind” (area 32) and language (area 44) have not evolved differentially higher requirements for metabolic support. Taken together, these findings suggest that greater metabolic consumption of human neocortical neurons relates to the energetic costs of maintaining expansive dendritic arbors and long-range projecting axons in the context of an enlarged brain. PMID:16938869

  8. Longitudinal Effects of Ketamine on Dendritic Architecture In Vivo in the Mouse Medial Frontal Cortex123

    PubMed Central

    Phoumthipphavong, Victoria; Barthas, Florent; Hassett, Samantha

    2016-01-01

    Abstract A single subanesthetic dose of ketamine, an NMDA receptor antagonist, leads to fast-acting antidepressant effects. In rodent models, systemic ketamine is associated with higher dendritic spine density in the prefrontal cortex, reflecting structural remodeling that may underlie the behavioral changes. However, turnover of dendritic spines is a dynamic process in vivo, and the longitudinal effects of ketamine on structural plasticity remain unclear. The purpose of the current study is to use subcellular resolution optical imaging to determine the time course of dendritic alterations in vivo following systemic ketamine administration in mice. We used two-photon microscopy to visualize repeatedly the same set of dendritic branches in the mouse medial frontal cortex (MFC) before and after a single injection of ketamine or saline. Compared to controls, ketamine-injected mice had higher dendritic spine density in MFC for up to 2 weeks. This prolonged increase in spine density was driven by an elevated spine formation rate, and not by changes in the spine elimination rate. A fraction of the new spines following ketamine injection was persistent, which is indicative of functional synapses. In a few cases, we also observed retraction of distal apical tuft branches on the day immediately after ketamine administration. These results indicate that following systemic ketamine administration, certain dendritic inputs in MFC are removed immediately, while others are added gradually. These dynamic structural modifications are consistent with a model of ketamine action in which the net effect is a rebalancing of synaptic inputs received by frontal cortical neurons. PMID:27066532

  9. Microglia recapitulate a hematopoietic master regulator network in the aging human frontal cortex.

    PubMed

    Wehrspaun, Claudia C; Haerty, Wilfried; Ponting, Chris P

    2015-08-01

    Microglia form the immune system of the brain. Previous studies in cell cultures and animal models suggest altered activation states and cellular senescence in the aged brain. Instead, we analyzed 3 transcriptome data sets from the postmortem frontal cortex of 381 control individuals to show that microglia gene markers assemble into a transcriptional module in a gene coexpression network. These markers predominantly represented M1 and M1/M2b activation phenotypes. Expression of genes in this module generally declines over the adult life span. This decrease was more pronounced in microglia surface receptors for microglia and/or neuron crosstalk than in markers for activation state phenotypes. In addition to these receptors for exogenous signals, microglia are controlled by brain-expressed regulatory factors. We identified a subnetwork of transcription factors, including RUNX1, IRF8, PU.1, and TAL1, which are master regulators (MRs) for the age-dependent microglia module. The causal contributions of these MRs on the microglia module were verified using publicly available ChIP-Seq data. Interactions of these key MRs were preserved in a protein-protein interaction network. Importantly, these MRs appear to be essential for regulating microglia homeostasis in the adult human frontal cortex in addition to their crucial roles in hematopoiesis and myeloid cell-fate decisions during embryogenesis. PMID:26002684

  10. What makes the dorsomedial frontal cortex active during reading the mental states of others?

    PubMed

    Isoda, Masaki; Noritake, Atsushi

    2013-01-01

    The dorsomedial frontal part of the cerebral cortex is consistently activated when people read the mental states of others, such as their beliefs, desires, and intentions, the ability known as having a theory of mind (ToM) or mentalizing. This ubiquitous finding has led many researchers to conclude that the dorsomedial frontal cortex (DMFC) constitutes a core component in mentalizing networks. Despite this, it remains unclear why the DMFC becomes active during ToM tasks. We argue that key psychological and behavioral aspects in mentalizing are closely associated with DMFC functions. These include executive inhibition, distinction between self and others, prediction under uncertainty, and perception of intentions, all of which are important for predicting others' intention and behavior. We review the literature supporting this claim, ranging in fields from developmental psychology to human neuroimaging and macaque electrophysiology. Because perceiving intentions in others' actions initiates mentalizing and forms the basis of virtually all types of social interaction, the fundamental issue in social neuroscience is to determine the aspects of physical entities that make an observer perceive that they are intentional beings and to clarify the neurobiological underpinnings of the perception of intentionality in others' actions. PMID:24367287

  11. The scarcity heuristic impacts reward processing within the medial-frontal cortex.

    PubMed

    Williams, Chad C; Saffer, Boaz Y; McCulloch, Robert B; Krigolson, Olave E

    2016-05-01

    Objects that are rare are often perceived to be inherently more valuable than objects that are abundant - a bias brought about in part by the scarcity heuristic. In the present study, we sought to test whether perception of rarity impacted reward evaluation within the human medial-frontal cortex. Here, participants played a gambling game in which they flipped rare and abundant 'cards' on a computer screen to win financial rewards while electroencephalographic data were recorded. Unbeknownst to participants, reward outcome and frequency was random and equivalent for both rare and abundant cards; thus, only a perception of scarcity was true. Analysis of the electroencephalographic data indicated that the P300 component of the event-related brain potential differed in amplitude for wins and losses following the selection of rare cards, but not following the selection of abundant cards. Importantly, then, we found that the perception of card rarity impacted reward processing even though reward feedback was independent of and subsequent to card selection. Our data indicate a top-down influence of the scarcity heuristic on reward evaluation, and specifically the processing of reward magnitude, within the human medial-frontal cortex. PMID:27031875

  12. Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome

    PubMed Central

    Mizuno, Kei; Tanaka, Masaaki; Tanabe, Hiroki C.; Joudoi, Takako; Kawatani, Junko; Shigihara, Yoshihito; Tomoda, Akemi; Miike, Teruhisa; Imai-Matsumura, Kyoko; Sadato, Norihiro; Watanabe, Yasuyoshi

    2015-01-01

    The ability to divide one's attention deteriorates in patients with childhood chronic fatigue syndrome (CCFS). We conducted a study using a dual verbal task to assess allocation of attentional resources to two simultaneous activities (picking out vowels and reading for story comprehension) and functional magnetic resonance imaging. Patients exhibited a much larger area of activation, recruiting additional frontal areas. The right middle frontal gyrus (MFG), which is included in the dorsolateral prefrontal cortex, of CCFS patients was specifically activated in both the single and dual tasks; this activation level was positively correlated with motivation scores for the tasks and accuracy of story comprehension. In addition, in patients, the dorsal anterior cingulate gyrus (dACC) and left MFG were activated only in the dual task, and activation levels of the dACC and left MFG were positively associated with the motivation and fatigue scores, respectively. Patients with CCFS exhibited a wider area of activated frontal regions related to attentional resources in order to increase their poorer task performance with massive mental effort. This is likely to be less efficient and costly in terms of energy requirements. It seems to be related to the pathophysiology of patients with CCFS and to cause a vicious cycle of further increases in fatigue. PMID:26594619

  13. Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome.

    PubMed

    Mizuno, Kei; Tanaka, Masaaki; Tanabe, Hiroki C; Joudoi, Takako; Kawatani, Junko; Shigihara, Yoshihito; Tomoda, Akemi; Miike, Teruhisa; Imai-Matsumura, Kyoko; Sadato, Norihiro; Watanabe, Yasuyoshi

    2015-01-01

    The ability to divide one's attention deteriorates in patients with childhood chronic fatigue syndrome (CCFS). We conducted a study using a dual verbal task to assess allocation of attentional resources to two simultaneous activities (picking out vowels and reading for story comprehension) and functional magnetic resonance imaging. Patients exhibited a much larger area of activation, recruiting additional frontal areas. The right middle frontal gyrus (MFG), which is included in the dorsolateral prefrontal cortex, of CCFS patients was specifically activated in both the single and dual tasks; this activation level was positively correlated with motivation scores for the tasks and accuracy of story comprehension. In addition, in patients, the dorsal anterior cingulate gyrus (dACC) and left MFG were activated only in the dual task, and activation levels of the dACC and left MFG were positively associated with the motivation and fatigue scores, respectively. Patients with CCFS exhibited a wider area of activated frontal regions related to attentional resources in order to increase their poorer task performance with massive mental effort. This is likely to be less efficient and costly in terms of energy requirements. It seems to be related to the pathophysiology of patients with CCFS and to cause a vicious cycle of further increases in fatigue. PMID:26594619

  14. Thalamocortical Connections of Functional Zones in Posterior Parietal Cortex and Frontal Cortex Motor Regions in New World Monkeys

    PubMed Central

    Stepniewska, Iwona; Burish, Mark J.; Kaas, Jon H.

    2010-01-01

    Posterior parietal cortex (PPC) links primate visual and motor systems and is central to visually guided action. Relating the anatomical connections of PPC to its neurophysiological functions may elucidate the organization of the parietal–frontal network. In owl and squirrel monkeys, long-duration electrical stimulation distinguished several functional zones within the PPC and motor/premotor cortex (M1/PM). Multijoint forelimb movements reminiscent of reach, defense, and grasp behaviors characterized each functional zone. In PPC, functional zones were organized parallel to the lateral sulcus. Thalamocortical connections of PPC and M1/PM zones were investigated with retrograde tracers. After several days of tracer transport, brains were processed, and labeled cells in thalamic nuclei were plotted. All PPC zones received dense inputs from the lateral posterior nucleus and the anterior pulvinar. PPC zones received additional projections from ventral lateral (VL) divisions of motor thalamus, which were also the primary source of input to M1/PM. Projections to PPC from rostral motor thalamus were sparse. Dense projections from ventral posterior (VP) nucleus of somatosensory thalamus distinguished the rostrolateral grasp zone from the other PPC zones. PPC connections with VL and VP provide links to cerebellar nuclei and the somatosensory system, respectively, that may integrate PPC functions with M1/PM. PMID:20080929

  15. Functional and Structural Remodeling of Glutamate Synapses in Prefrontal and Frontal Cortex Induced by Behavioral Stress

    PubMed Central

    Musazzi, Laura; Treccani, Giulia; Popoli, Maurizio

    2015-01-01

    Increasing evidence has shown that the pathophysiology of neuropsychiatric disorders, including mood disorders, is associated with abnormal function and regulation of the glutamatergic system. Consistently, preclinical studies on stress-based animal models of pathology showed that glucocorticoids and stress exert crucial effects on neuronal excitability and function, especially in cortical and limbic areas. In prefrontal and frontal cortex, acute stress was shown to induce enhancement of glutamate release/transmission dependent on activation of corticosterone receptors. Although the mechanisms whereby stress affects glutamate transmission have not yet been fully understood, it was shown that synaptic, non-genomic action of corticosterone is required to increase the readily releasable pool of glutamate vesicles, but is not sufficient to enhance transmission in prefrontal and frontal cortex. Slower, partly genomic mechanisms are probably necessary for the enhancement of glutamate transmission induced by stress. Combined evidence has suggested that the changes in glutamate release and transmission are responsible for the dendritic remodeling and morphological changes induced by stress and it has been argued that sustained alterations of glutamate transmission may play a key role in the long-term structural/functional changes associated with mood disorders in patients. Intriguingly, modifications of the glutamatergic system induced by stress in the prefrontal cortex seem to be biphasic. Indeed, while the fast response to stress suggests an enhancement in the number of excitatory synapses, synaptic transmission and working memory, long-term adaptive changes – including those consequent to chronic stress – induce opposite effects. Better knowledge of the cellular effectors involved in this biphasic effect of stress may be useful to understand the pathophysiology of stress-related disorders, and open new paths for the development of therapeutic approaches. PMID

  16. Reduced frontal cortex thickness and cortical volume associated with pathological narcissism.

    PubMed

    Mao, Yu; Sang, Na; Wang, Yongchao; Hou, Xin; Huang, Hui; Wei, Dongtao; Zhang, Jinfu; Qiu, Jiang

    2016-07-22

    Pathological narcissism is often characterized by arrogant behavior, a lack of empathy, and willingness to exploit other individuals. Generally, individuals with high levels of narcissism are more likely to suffer mental disorders. However, the brain structural basis of individual pathological narcissism trait among healthy people has not yet been investigated with surface-based morphometry. Thus, in this study, we investigated the relationship between cortical thickness (CT), cortical volume (CV), and individual pathological narcissism in a large healthy sample of 176 college students. Multiple regression was used to analyze the correlation between regional CT, CV, and the total Pathological Narcissism Inventory (PNI) score, adjusting for age, sex, and total intracranial volume. The results showed that the PNI score was significantly negatively associated with CT and CV in the right dorsolateral prefrontal cortex (DLPFC, key region of the central executive network, CEN), which might be associated with impaired emotion regulation processes. Furthermore, the PNI score showed significant negative associations with CV in the right postcentral gyrus, left medial prefrontal cortex (MPFC), and the CT in the right inferior frontal cortex (IFG, overlap with social brain network), which may be related to impairments in social cognition. Together, these findings suggest a unique structural basis for individual differences in pathological narcissism, distributed across different gray matter regions of the social brain network and CEN. PMID:27129440

  17. Distributed representations of rule identity and rule order in human frontal cortex and striatum.

    PubMed

    Reverberi, Carlo; Görgen, Kai; Haynes, John-Dylan

    2012-11-28

    Humans are able to flexibly devise and implement rules to reach their desired goals. For simple situations, we can use single rules, such as "if traffic light is green then cross the street." In most cases, however, more complex rule sets are required, involving the integration of multiple layers of control. Although it has been shown that prefrontal cortex is important for rule representation, it has remained unclear how the brain encodes more complex rule sets. Here, we investigate how the brain represents the order in which different parts of a rule set are evaluated. Participants had to follow compound rule sets that involved the concurrent application of two single rules in a specific order, where one of the rules always had to be evaluated first. The rules and their assigned order were independently manipulated. By applying multivariate decoding to fMRI data, we found that the identity of the current rule was encoded in a frontostriatal network involving right ventrolateral prefrontal cortex, right superior frontal gyrus, and dorsal striatum. In contrast, rule order could be decoded in the dorsal striatum and in the right premotor cortex. The nonhomogeneous distribution of information across brain areas was confirmed by follow-up analyses focused on relevant regions of interest. We argue that the brain encodes complex rule sets by "decomposing" them in their constituent features, which are represented in different brain areas, according to the aspect of information to be maintained. PMID:23197733

  18. Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain

    PubMed Central

    Lieblein-Boff, Jacqueline C.; Johnson, Elizabeth J.; Kennedy, Adam D.; Lai, Chron-Si; Kuchan, Matthew J.

    2015-01-01

    Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula, and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and postmortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem metabolomic analyses were performed on human infant brain tissues in three regions important for learning and memory: the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510) were excluded. In addition, moderate correlations with xenobiotic relationships (2) or those driven by single outliers (3) were excluded from further study. Lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region—specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development. PMID:26317757

  19. Echo-planar magnetic resonance imaging studies of frontal cortex activation during word generation in humans.

    PubMed Central

    McCarthy, G; Blamire, A M; Rothman, D L; Gruetter, R; Shulman, R G

    1993-01-01

    Nine subjects were studied by high-speed magnetic resonance imaging while performing language-based tasks. Subjects were asked either to repeat or to generate verbs associated with nouns read by an experimenter while magnetic resonance images were obtained of the left inferior frontal lobe. The echo-planar imaging sequence was used with a gradient echo time of 70 ms to give an apparent transverse relaxation time weighting (T2* that is sensitive to local hemoglobin levels. Images were acquired every 3 s (repetition time) in series of 32. In plane resolution was 6 x 4.5 mm and slice thickness was 10 mm. An increase in signal accompanied performance of the tasks, with significantly more activation for verb generation than for repeating. The activation effect occurred within 3 s after task onset and could be observed in single images from individual subjects. The primary focus of activation appeared in gray matter along a sulcus anterior to the lateral sulcus that included the anterior insula, Brodmann's area 47, and extending to area 10. Little or no activation of this region was found for a passive listening, covert generation, or mouth-movement control tasks. Significant activation was also found for a homologous region in the right frontal cortex but not for control regions in calcarine cortex. These results are consistent with prior studies that have used positron emission tomography imaging with 15O-labeled water as a blood flow tracer. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8506340

  20. Topographic analysis of individual activation patterns in medial frontal cortex in schizophrenia.

    PubMed

    Stern, Emily R; Welsh, Robert C; Fitzgerald, Kate D; Taylor, Stephan F

    2009-07-01

    Individual variability in the location of neural activations poses a unique problem for neuroimaging studies employing group averaging techniques to investigate the neural bases of cognitive and emotional functions. This may be especially challenging for studies examining patient groups, which often have limited sample sizes and increased intersubject variability. In particular, medial frontal cortex (MFC) dysfunction is thought to underlie performance monitoring dysfunction among patients with schizophrenia, yet previous studies using group averaging to compare schizophrenic patients to controls have yielded conflicting results. To examine individual activations in MFC associated with two aspects of performance monitoring, interference and error processing, functional magnetic resonance imaging data were acquired while 17 patients with schizophrenia and 21 healthy controls (HCs) performed an event-related version of the multisource interference task. Comparisons of averaged data revealed few differences between the groups. By contrast, topographic analysis of individual activations for errors showed that control subjects exhibited activations spanning across both posterior and anterior regions of MFC while patients primarily activated posterior MFC, possibly reflecting an impaired emotional response to errors in schizophrenia. This discrepancy between topographic and group-averaged results may be due to the significant dispersion among individual activations, particularly in HCs, highlighting the importance of considering intersubject variability when interpreting the medial frontal response to error commission. PMID:18819107

  1. The role of the frontal cortex in memory: an investigation of the Von Restorff effect

    PubMed Central

    Elhalal, Anat; Davelaar, Eddy J.; Usher, Marius

    2014-01-01

    Evidence from neuropsychology and neuroimaging indicate that the pre-frontal cortex (PFC) plays an important role in human memory. Although frontal patients are able to form new memories, these memories appear qualitatively different from those of controls by lacking distinctiveness. Neuroimaging studies of memory indicate activation in the PFC under deep encoding conditions, and under conditions of semantic elaboration. Based on these results, we hypothesize that the PFC enhances memory by extracting differences and commonalities in the studied material. To test this hypothesis, we carried out an experimental investigation to test the relationship between the PFC-dependent factors and semantic factors associated with common and specific features of words. These experiments were performed using Free-Recall of word lists with healthy adults, exploiting the correlation between PFC function and fluid intelligence. As predicted, a correlation was found between fluid intelligence and the Von-Restorff effect (better memory for semantic isolates, e.g., isolate “cat” within category members of “fruit”). Moreover, memory for the semantic isolate was found to depend on the isolate's serial position. The isolate item tends to be recalled first, in comparison to non-isolates, suggesting that the process interacts with short term memory. These results are captured within a computational model of free recall, which includes a PFC mechanism that is sensitive to both commonality and distinctiveness, sustaining a trade-off between the two. PMID:25018721

  2. An Herbal Nasal Drop Enhanced Frontal and Anterior Cingulate Cortex Activity

    PubMed Central

    Chan, Agnes S.; Cheung, Mei-chun; Sze, Sophia L.; Leung, Winnie W.; Shi, Dejian

    2011-01-01

    The present study examined the neuro-electrophysiological activity of the brain associated with the application of a herbal remedy developed by a Shaolin monk based upon the Chan healing principle of clearing the orifices (i.e., the nasal cavities). A repeated-measures design was used. Fourteen normal adults were administered herbal remedy and saline solution intranasally on separate sessions. Two intervals of eyes-closed resting EEG data were obtained individually before and after each administration. Results showed that only the herbal remedy but not the saline solution induced elevation in cordance, an index correlated with cerebral perfusion, in the anterior brain region. In addition, the activity of the anterior cingulate cortex (ACC), as examined by the LORETA analysis, was also increased after the application of the herbal remedy but not saline solution. The present study provided some preliminary evidence suggesting that the herbal nasal drop enhanced the activity of the frontal lobe and ACC. Implications for the potential clinical application of the herbal remedy to treat patients with frontal lobe disorders were discussed. PMID:19996154

  3. Manatee cerebral cortex: cytoarchitecture of the frontal region in Trichechus manatus latirostris.

    PubMed

    Reep, R L; Johnson, J I; Switzer, R C; Welker, W I

    1989-01-01

    Members of the order Sirenia are unique among mammals in being the only totally aquatic herbivores. They display correspondingly specialized physiological, behavioral and anatomical features. There have been few reports concerning sirenian neuroanatomy, and most of these have consisted of gross anatomical observations. Our interest in Sirenia stems from the desire to understand neuroanatomical specializations in the context of behavior and the effort to elucidate trends in mammalian brain evolution. The architecture of frontal regions of cerebral cortex was investigated in several brains of the Florida manatee, Trichechus manatus latirostris. Through observation of sections stained for Nissl substance or myelinated fibers, several distinct cortical areas were identified on the basis of laminar organization. These range from areas with poorly defined laminae to those having 6 well-defined layers, some of which exhibit sublayers. Two cortical areas exhibit pronounced cell clusters in layer VI, and these stain positively for acetylcholinesterase and cytochrome oxidase. We hypothesize that these clusters may be involved in perioral tactile bristle function. Certain of our findings are consistent with previous observations in the literature on the brains of dugongs. On the basis of their lamination patterns, these frontal cortical areas appear to be organized into concentric zones of allocortex, mesocortex and isocortex. PMID:2611642

  4. The effects of chronic fluoxetine treatment following injury of medial frontal cortex in mice.

    PubMed

    McAllister, Brendan B; Spanswick, Simon C; Patel, Payal P; Barneto, Alison A; Dyck, Richard H

    2015-09-01

    Injury of the brain is a leading cause of long-term disability. Recent evidence indicates that the selective serotonin reuptake inhibitor drug fluoxetine may be beneficial when administered following brain injury. However, its potential to promote recovery and the mechanisms by which it might do so require further characterization. In the present experiment, fluoxetine was administered to mice for 4 weeks following injury of medial frontal cortex (MFC). MFC injury altered behavior, reducing locomotion, decreasing swim speed in the Morris water task, and decreasing anxiety-like behavior in the elevated plus maze. Fluoxetine treatment did not affect these behavioral alterations, but it did increase the social dominance of the injured mice, as assessed by the tube test. Fluoxetine treatment also hastened learning of a T-maze position discrimination task, independently of lesion condition. Anatomically, fluoxetine failed to decrease lesion size, increase the survival of cells born 1-week post injury in the hippocampal dentate gyrus, or reverse the reduction in spine density in layer II/III pyramidal neurons in cingulate cortex caused by the lesions. Fluoxetine did, however, increase the dendritic arborization of these cells, which was reduced in the mice with lesions. Thus, while not all the effects of MFC injury were ameliorated, the behavioral outcome of mice with MFC injuries was improved, and one of the neuroanatomical sequelae of the lesions counteracted, by chronic fluoxetine, further contributing to the evidence that fluoxetine could be a useful treatment following brain injury. PMID:25956871

  5. Dorso-Lateral Frontal Cortex of the Ferret Encodes Perceptual Difficulty during Visual Discrimination

    PubMed Central

    Zhou, Zhe Charles; Yu, Chunxiu; Sellers, Kristin K.; Fröhlich, Flavio

    2016-01-01

    Visual discrimination requires sensory processing followed by a perceptual decision. Despite a growing understanding of visual areas in this behavior, it is unclear what role top-down signals from prefrontal cortex play, in particular as a function of perceptual difficulty. To address this gap, we investigated how neurons in dorso-lateral frontal cortex (dl-FC) of freely-moving ferrets encode task variables in a two-alternative forced choice visual discrimination task with high- and low-contrast visual input. About two-thirds of all recorded neurons in dl-FC were modulated by at least one of the two task variables, task difficulty and target location. More neurons in dl-FC preferred the hard trials; no such preference bias was found for target location. In individual neurons, this preference for specific task types was limited to brief epochs. Finally, optogenetic stimulation confirmed the functional role of the activity in dl-FC before target touch; suppression of activity in pyramidal neurons with the ArchT silencing opsin resulted in a decrease in reaction time to touch the target but not to retrieve reward. In conclusion, dl-FC activity is differentially recruited for high perceptual difficulty in the freely-moving ferret and the resulting signal may provide top-down behavioral inhibition. PMID:27025995

  6. Antiamnesic effect of acyl-prolyl-containing dipeptide (GVS-111) in compression-induced damage to frontal cortex.

    PubMed

    Romanova, G A; Mirzoev, T K; Barskov, I V; Victorov, I V; Gudasheva, T A; Ostrovskaya, R U

    2000-09-01

    Antiamnestic effect of acyl-prolyl-containing dipeptide GVS-111 was demonstrated in rats with bilateral compression-induced damage to the frontal cortex. Both intraperitoneal and oral administration of the dipeptide improved retrieval of passive avoidance responses in rats with compression-induced cerebral ischemia compared to untreated controls. PMID:11177261

  7. Frontal Eye Fields Control Attentional Modulation of Alpha and Gamma Oscillations in Contralateral Occipitoparietal Cortex

    PubMed Central

    O'Shea, Jacinta; Jensen, Ole; Bergmann, Til O.

    2015-01-01

    Covertly directing visuospatial attention produces a frequency-specific modulation of neuronal oscillations in occipital and parietal cortices: anticipatory alpha (8–12 Hz) power decreases contralateral and increases ipsilateral to attention, whereas stimulus-induced gamma (>40 Hz) power is boosted contralaterally and attenuated ipsilaterally. These modulations must be under top-down control; however, the control mechanisms are not yet fully understood. Here we investigated the causal contribution of the human frontal eye field (FEF) by combining repetitive transcranial magnetic stimulation (TMS) with subsequent magnetoencephalography. Following inhibitory theta burst stimulation to the left FEF, right FEF, or vertex, participants performed a visual discrimination task requiring covert attention to either visual hemifield. Both left and right FEF TMS caused marked attenuation of alpha modulation in the occipitoparietal cortex. Notably, alpha modulation was consistently reduced in the hemisphere contralateral to stimulation, leaving the ipsilateral hemisphere relatively unaffected. Additionally, right FEF TMS enhanced gamma modulation in left visual cortex. Behaviorally, TMS caused a relative slowing of response times to targets contralateral to stimulation during the early task period. Our results suggest that left and right FEF are causally involved in the attentional top-down control of anticipatory alpha power in the contralateral visual system, whereas a right-hemispheric dominance seems to exist for control of stimulus-induced gamma power. These findings contrast the assumption of primarily intrahemispheric connectivity between FEF and parietal cortex, emphasizing the relevance of interhemispheric interactions. The contralaterality of effects may result from a transient functional reorganization of the dorsal attention network after inhibition of either FEF. PMID:25632139

  8. Cortical thickness of superior frontal cortex predicts impulsiveness and perceptual reasoning in adolescence.

    PubMed

    Schilling, C; Kühn, S; Paus, T; Romanowski, A; Banaschewski, T; Barbot, A; Barker, G J; Brühl, R; Büchel, C; Conrod, P J; Dalley, J W; Flor, H; Ittermann, B; Ivanov, N; Mann, K; Martinot, J-L; Nees, F; Rietschel, M; Robbins, T W; Smolka, M N; Ströhle, A; Kathmann, N; Garavan, H; Heinz, A; Schumann, G; Gallinat, J

    2013-05-01

    Impulsiveness is a pivotal personality trait representing a core domain in all major personality inventories. Recently, impulsiveness has been identified as an important modulator of cognitive processing, particularly in tasks that require the processing of large amounts of information. Although brain imaging studies have implicated the prefrontal cortex to be a common underlying representation of impulsiveness and related cognitive functioning, to date a fine-grain and detailed morphometric analysis has not been carried out. On the basis of ahigh-resolution magnetic resonance scans acquired in 1620 healthy adolescents (IMAGEN), the individual cortical thickness (CT) was estimated. Correlations between Cloninger's impulsiveness and CT were studied in an entire cortex analysis. The cluster identified was tested for associations with performance in perceptual reasoning tasks of the Wechsler Intelligence Scale for Children (WISC IV). We observed a significant inverse correlation between trait impulsiveness and CT of the left superior frontal cortex (SFC; Monte Carlo Simulation P<0.01). CT within this cluster correlated with perceptual reasoning scores (Bonferroni corrected) of the WISC IV. On the basis of a large sample of adolescents, we identified an extended area in the SFC as a correlate of impulsiveness, which appears to be in line with the trait character of this prominent personality facet. The association of SFC thickness with perceptual reasoning argues for a common neurobiological basis of personality and specific cognitive domains comprising attention, spatial reasoning and response selection. The results may facilitate the understanding of the role of impulsiveness in several psychiatric disorders associated with prefrontal dysfunctions and cognitive deficits. PMID:22665261

  9. Ipsi- and contralateral frontal cortex oxygenation during handgrip task does not follow decrease on maximal force output.

    PubMed

    Kuboyama, Naomi; Shibuya, Kenichi

    2015-01-01

    The effect of fatiguing exercise on the ipsi- and contralateral frontal cortex has not been fully clarified. The purpose of this study was to investigate by near-infrared spectroscopy (NIRS) the frontal cortex oxygenation response to a prolonged fatiguing repetitive handgrip exercise performed at maximal voluntary contraction. It was found a significant oxyhemoglobin concentration ([HbO2]) increase (p < 0.05), accompanied by a smaller and delayed deoxyhemoglobin concentration ([Hb]) decrease (p < 0.05), in both hemispheres. Then, it was indicated higher delayed oxygenation in ipsilateral oxygenation compared to contralateral oxygenation. These results provide further evidence that the complemental interaction between the ipsilateral and contralateral cortex during the fatiguing maximal exercise. PMID:26536889

  10. Chronic Ritalin Administration during Adulthood Increases Serotonin Pool in Rat Medial Frontal Cortex

    PubMed Central

    Daniali, Samira; Nahavandi, Arezo; Madjd, Zahra; Shahbazi, Ali; Niknazar, Somayeh; Shahbazzadeh, Delavar

    2013-01-01

    Background: Ritalin has high tendency to be abused. It has been the main indication to control attention deficit hyperactivity disorder. The college students may seek for it to improve their memory, decrease the need for sleep (especially during exams), which at least partially, can be related to serotonergic system. Therefore, it seems worthy to evaluate the effect of Ritalin intake on mature brain. There are many studies on Ritalin effect on developing brain, but only few studies on adults are available. This study was undertaken to find Ritalin effect on serotonin transporter (SERT) density in medial frontal cortex (MFC) of mature rat. Methods: Thirty male Wistar rats were used in the study. Rats were assigned into five groups (n = 6 per group): one control, two Ritalin and two vehicle groups. Twelve rats received Ritalin (20 mg/kg/twice a day) orally for eleven continuous days. After one week of withdrawal and another two weeks of rest, in order to evaluate short-term effects of Ritalin, six rats were sacrificed. Another six rats were studied to detect the long-term effects of Ritalin; therefore, they were sacrificed 12 weeks after the previous group. The immunohistochemistry was performed to evaluate the results. Results: Immunohistochemistry studies showed a higher density of SERT in both 2 and 12 weeks after withdrawal from Ritalin intake in MFC of rat and there was no significant difference between these two groups. Conclusions: Our findings demonstrated both short- and long-term effects of Ritalin on frontal serotonergic system after withdrawal period. PMID:23748891

  11. Aberrant network integrity of the inferior frontal cortex in women with anorexia nervosa

    PubMed Central

    Kullmann, Stephanie; Giel, Katrin E.; Teufel, Martin; Thiel, Ansgar; Zipfel, Stephan; Preissl, Hubert

    2014-01-01

    Neuroimaging studies investigating the neural profile of anorexia nervosa (AN) have revealed a predominant imbalance between the reward and inhibition systems of the brain, which are also hallmark characteristics of the disorder. However, little is known whether these changes can also be determined independent of task condition, using resting-state functional magnetic resonance imaging, in currently ill AN patients. Therefore the aim of our study was to investigate resting-state connectivity in AN patients (n = 12) compared to healthy athlete (n = 12) and non-athlete (n = 14) controls. For this purpose, we used degree centrality to investigate functional connectivity of the whole-brain network and then Granger causality to analyze effective connectivity (EC), to understand directional aspects of potential alterations. We were able to show that the bilateral inferior frontal gyrus (IFG) is a region of special functional importance within the whole-brain network, in AN patients, revealing reduced functional connectivity compared to both healthy control groups. Furthermore, we found decreased EC from the right IFG to the midcingulum and increased EC from the bilateral orbitofrontal gyrus to the right IFG. For the left IFG, we only observed increased EC from the bilateral insula to the left IFG. These results suggest that AN patients have reduced connectivity within the cognitive control system of the brain and increased connectivity within regions important for salience processing. Due to its fundamental role in inhibitory behavior, including motor response, altered integrity of the inferior frontal cortex could contribute to hyperactivity in AN. PMID:24936412

  12. Dissociable Roles of Dorsolateral Prefrontal Cortex and Frontal Eye Fields During Saccadic Eye Movements

    PubMed Central

    Cameron, Ian G. M.; Riddle, Justin M.; D’Esposito, Mark

    2015-01-01

    The dorsolateral prefrontal cortex (DLPFC) and the frontal eye fields (FEF) have both been implicated in the executive control of saccades, yet possible dissociable roles of each region have not been established. Specifically, both establishing a “task set” as well as suppressing an inappropriate response have been linked to DLPFC and FEF activity, with behavioral outcome measures of these mechanisms mainly being the percentage of pro-saccade errors made on anti-saccade trials. We used continuous theta-burst stimulation (cTBS) to disrupt FEF or DLPFC function in humans during an anti-saccade task to assess the causal role of these regions in these executive control processes, and in programming saccades towards (pro-saccade) or away (anti-saccade) from visual targets. After right FEF cTBS, as compared to control cTBS to the right primary somatosensory cortex (rS1), anti-saccade amplitude of the first saccade decreased and the number of anti-saccades to acquire final position increased; however direction errors to the visual target were not different. In contrast, after left DLPFC cTBS, as compared to left S1 cTBS, subjects displayed greater direction errors for contralateral anti-saccades; however, there were no impairments on the number of saccades or the saccade amplitude. These results are consistent with the notion that DLPFC is necessary for executive control of saccades, whereas FEF is necessary for visuo-motor aspects of anti-saccade programming. PMID:26635572

  13. Patterns of social-experience-related c-fos and Arc expression in the frontal cortices of rats exposed to saccharin or moderate levels of ethanol during prenatal brain development

    PubMed Central

    Hamilton, Derek A.; Candelaria-Cook, Felicha T.; Akers, Katherine G.; Rice, James P.; Maes, Levi I.; Rosenberg, Martina; Valenzuela, C. Fernando; Savage, Daniel D.

    2010-01-01

    Recent findings from our laboratory indicate that alterations in frontal cortex function, structural plasticity, and related social behaviors are persistent consequences of exposure to moderate levels of ethanol during prenatal brain development [24]. Fetal-ethanol-related reductions in the expression of the immediate early genes (IEGs) c-fos and Arc and alterations in dendritic spine density in ventrolateral and medial aspects of frontal cortex suggest a dissociation reminiscent of that described by Kolb et al. [38] in which these aspects of frontal cortex undergo reciprocal experience-dependent changes. In addition to providing a brief review of the available data on social behavior and frontal cortex function in fetal-ethanol-exposed rats, the present paper presents novel data on social-experience-related IEG expression in four regions of frontal cortex (Zilles LO, VLO, Fr1, Fr2) that are evaluated alongside our prior data from AID and Cg3. Social experience in normal rats was related to a distinct pattern of IEG expression in ventrolateral and medial aspects of frontal cortex, with generally greater expression observed in ventrolateral frontal cortex. In contrast, weaker expression was observed in all aspects of frontal cortex in ethanol-exposed rats, with the exception of an experience-related increase in the medial agranular cortex. Behaviors related to social investigation and wrestling/boxing were differentially correlated with patterns of activity-related IEG expression in the regions under investigation for saccharin- and ethanol-exposed rats. These observations suggest that recruitment and expression of IEGs in frontal cortex following social experience are potentially important for understanding the long-term consequences of moderate prenatal ethanol exposure on frontal cortex function, synaptic plasticity, and related behaviors. PMID:20570698

  14. A causal role for posterior medial frontal cortex in choice-induced preference change.

    PubMed

    Izuma, Keise; Akula, Shyam; Murayama, Kou; Wu, Daw-An; Iacoboni, Marco; Adolphs, Ralph

    2015-02-25

    After a person chooses between two items, preference for the chosen item will increase and preference for the unchosen item will decrease because of the choice made. In other words, we tend to justify or rationalize our past behavior by changing our attitude. This phenomenon of choice-induced preference change has been traditionally explained by cognitive dissonance theory. Choosing something that is disliked or not choosing something that is liked are both cognitively inconsistent and, to reduce this inconsistency, people tend to change their subsequently stated preference in accordance with their past choices. Previously, human neuroimaging studies identified posterior medial frontal cortex (pMFC) as a key brain region involved in cognitive dissonance. However, it remains unknown whether the pMFC plays a causal role in inducing preference change after cognitive dissonance. Here, we demonstrate that 25 min, 1 Hz repetitive transcranial magnetic stimulation applied over the pMFC significantly reduces choice-induced preference change compared with sham stimulation or control stimulation over a different brain region, demonstrating a causal role for the pMFC. PMID:25716858

  15. Microglia and astrocyte activation in the frontal cortex of rats with experimental autoimmune encephalomyelitis.

    PubMed

    Chanaday, N L; Roth, G A

    2016-02-01

    Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model for the human disease multiple sclerosis (MS), a demyelinating and neurodegenerative pathology of the central nervous system. Both diseases share physiopathological and clinical characteristics, mainly associated with a neuroinflammatory process that leads to a set of motor, sensory, and cognitive symptoms. In MS, gray matter atrophy is related to the emergence of cognitive deficits and contributes to clinical progression. In particular, injury and dysfunction in certain areas of the frontal cortex (FrCx) have been related to the development of cognitive impairments with high incidence, like central fatigue and executive dysfunction. In the present work we show the presence of region-specific microglia and astrocyte activation in the FrCx, during the first hours of acute EAE onset. It is accompanied by the production of the pro-inflammatory cytokines IL-6 and TNF-α, in the absence of detectable leukocyte infiltration. These findings expand previous studies showing presynaptic neural dysfunction occurring at the FrCx and might contribute to the understanding of the mechanisms involved in the genesis and prevalence of common MS symptoms. PMID:26679600

  16. Glutamine synthetase activity and glutamate uptake in hippocampus and frontal cortex in portal hypertensive rats

    PubMed Central

    Acosta, Gabriela Beatriz; Fernández, María Alejandra; Roselló, Diego Martín; Tomaro, María Luján; Balestrasse, Karina; Lemberg, Abraham

    2009-01-01

    AIM: To study glutamine synthetase (GS) activity and glutamate uptake in the hippocampus and frontal cortex (FC) from rats with prehepatic portal vein hypertension. METHODS: Male Wistar rats were divided into sham-operated group and a portal hypertension (PH) group with a regulated stricture of the portal vein. Animals were sacrificed by decapitation 14 d after portal vein stricture. GS activity was determined in the hippocampus and FC. Specific uptake of radiolabeled L-glutamate was studied using synaptosome-enriched fractions that were freshly prepared from both brain areas. RESULTS: We observed that the activity of GS increased in the hippocampus of PH rats, as compared to control animals, and decreased in the FC. A significant decrease in glutamate uptake was found in both brain areas, and was more marked in the hippocampus. The decrease in glutamate uptake might have been caused by a deficient transport function, significantly and persistent increase in this excitatory neurotransmitter activity. CONCLUSION: The presence of moderate ammonia blood levels may add to the toxicity of excitotoxic glutamate in the brain, which causes alterations in brain function. Portal vein stricture that causes portal hypertension modifies the normal function in some brain regions. PMID:19533812

  17. A multivariate approach to aggression and the orbital frontal cortex in psychiatric patients.

    PubMed

    Gansler, David A; McLaughlin, Nicole C R; Iguchi, Lisa; Jerram, Matthew; Moore, Dana W; Bhadelia, Rafeeque; Fulwiler, Carl

    2009-03-31

    The association between orbital frontal cortex (OFC) volume and aggression was investigated in an at-risk psychiatric population. Forty-one psychiatric patients were referred for magnetic resonance imaging and a standardized psychometric assessment of aggression (Lifetime History of Aggression-Revised). Nineteen matched controls had lower levels of aggression and greater OFC volume, establishing the appropriateness of the psychiatric group for studying aggression pathophysiology. Consistent with study hypotheses, left OFC gray matter volume predicted 34% of the variance in self-reported aggression ratings. When impulsivity was not controlled for, left OFC gray matter only accounted for 26% of aggression variance, suggesting a complex relationship between impulsivity and OFC-aggression pathophysiology. Contrary to study hypotheses, right OFC gray matter volume did not predict degree of aggressive behavior. Current models do not account for lateralization, yet this may be quite important. Greater consideration should be given to laterality in OFC regulation of social/emotional behavior. Regulatory focus theory, positing two motivational systems, promotion and prevention, lateralized to the left and right hemispheres, respectively, may provide an explanatory framework for these results. Dysregulation of the left hemisphere 'promotion' motivational system may help to explain the aggressive behavior present in psychiatric populations. PMID:19216060

  18. Frontal Cortex Transcriptome Analysis of Mice Exposed to Electronic Cigarettes During Early Life Stages.

    PubMed

    Lauterstein, Dana E; Tijerina, Pamella B; Corbett, Kevin; Akgol Oksuz, Betul; Shen, Steven S; Gordon, Terry; Klein, Catherine B; Zelikoff, Judith T

    2016-01-01

    Electronic cigarettes (e-cigarettes), battery-powered devices containing nicotine, glycerin, propylene glycol, flavorings, and other substances, are increasing in popularity. They pose a potential threat to the developing brain, as nicotine is a known neurotoxicant. We hypothesized that exposure to e-cigarettes during early life stages induce changes in central nervous system (CNS) transcriptome associated with adverse neurobiological outcomes and long-term disease states. To test the hypothesis, pregnant C57BL/6 mice were exposed daily (via whole body inhalation) throughout gestation (3 h/day; 5 days/week) to aerosols produced from e-cigarettes either with nicotine (13-16 mg/mL) or without nicotine; following birth, pups and dams were exposed together to e-cigarette aerosols throughout lactation beginning at postnatal day (PND) 4-6 and using the same exposure conditions employed during gestational exposure. Following exposure, frontal cortex recovered from ~one-month-old male and female offspring were excised and analyzed for gene expression by RNA Sequencing (RNA-Seq). Comparisons between the treatment groups revealed that e-cigarette constituents other than nicotine might be partly responsible for the observed biological effects. Transcriptome alterations in both offspring sexes and treatment groups were all significantly associated with downstream adverse neurobiological outcomes. Results from this study demonstrate that e-cigarette exposure during early life alters CNS development potentially leading to chronic neuropathology. PMID:27077873

  19. Sex and the frontal cortex: A developmental CT study in the spotted hyena.

    PubMed

    Arsznov, Bradley M; Lundrigan, Barbara L; Holekamp, Kay E; Sakai, Sharleen T

    2010-01-01

    The purpose of this study was to examine developmental and individual variation in total endocranial volume and regional brain volumes, including the anterior cerebrum, posterior cerebrum and cerebellum/brain stem, in the spotted hyena (Crocuta crocuta). The spotted hyena is a highly gregarious animal noted for living in large, hierarchically organized groups. The social lives of male and female spotted hyenas do not differ until after puberty, when males disperse from the natal group, while females remain philopatric. Here we sought to determine whether the divergent life histories of male and female spotted hyenas are linked to differences in brain size or organization. Three-dimensional virtual endocasts were created using computed tomography from 46 spotted hyenas skulls (23 females, 22 males, 1 unknown sex) ranging in age from 1 day to 18 years. Brain volume and skull length were highly correlated (r = 0.91), and both reached asymptotic values by 34 months of age. Analyses of total endocranial volume (relative to skull length) and cerebellum/brain stem volume (relative to total endocranial volume) revealed no sex differences. However, relative anterior cerebrum volume, comprised mainly of frontal cortex, was significantly greater in adult males than adult females, and relative posterior cerebrum volume was greater in adult females than adult males. We hypothesize that the demands of neural processing underlying enhanced social cognition required for successful male transfer between matriarchical social groups at dispersal may be greater than cognitive demands on philopatric females. PMID:21088374

  20. Frontal Cortex Transcriptome Analysis of Mice Exposed to Electronic Cigarettes During Early Life Stages

    PubMed Central

    Lauterstein, Dana E.; Tijerina, Pamella B.; Corbett, Kevin; Akgol Oksuz, Betul; Shen, Steven S.; Gordon, Terry; Klein, Catherine B.; Zelikoff, Judith T.

    2016-01-01

    Electronic cigarettes (e-cigarettes), battery-powered devices containing nicotine, glycerin, propylene glycol, flavorings, and other substances, are increasing in popularity. They pose a potential threat to the developing brain, as nicotine is a known neurotoxicant. We hypothesized that exposure to e-cigarettes during early life stages induce changes in central nervous system (CNS) transcriptome associated with adverse neurobiological outcomes and long-term disease states. To test the hypothesis, pregnant C57BL/6 mice were exposed daily (via whole body inhalation) throughout gestation (3 h/day; 5 days/week) to aerosols produced from e-cigarettes either with nicotine (13–16 mg/mL) or without nicotine; following birth, pups and dams were exposed together to e-cigarette aerosols throughout lactation beginning at postnatal day (PND) 4–6 and using the same exposure conditions employed during gestational exposure. Following exposure, frontal cortex recovered from ~one-month-old male and female offspring were excised and analyzed for gene expression by RNA Sequencing (RNA-Seq). Comparisons between the treatment groups revealed that e-cigarette constituents other than nicotine might be partly responsible for the observed biological effects. Transcriptome alterations in both offspring sexes and treatment groups were all significantly associated with downstream adverse neurobiological outcomes. Results from this study demonstrate that e-cigarette exposure during early life alters CNS development potentially leading to chronic neuropathology. PMID:27077873

  1. Shared changes in gene expression in frontal cortex of four genetically modified mouse models of depression.

    PubMed

    Hoyle, D; Juhasz, G; Aso, E; Chase, D; del Rio, J; Fabre, V; Hamon, M; Lanfumey, L; Lesch, K-P; Maldonado, R; Serra, M-A; Sharp, T; Tordera, R; Toro, C; Deakin, J F W

    2011-01-01

    This study aimed to identify whether genetic manipulation of four systems implicated in the pathogenesis of depression converge on shared molecular processes underpinning depression-like behaviour in mice. Altered 5HT function was modelled using the 5-HT transporter knock out mouse, impaired glucocorticoid receptor (GR) function using an antisense-induced knock down mouse, disrupted glutamate function using a heterozygous KO of the vesicular glutamate transporter 1 gene, and impaired cannabinoid signalling using the cannabinoid 1 receptor KO mouse. All 4 four genetically modified mice were previously shown to show exaggerated helpless behaviour compared to wild-type controls and variable degrees of anxiety and anhedonic behaviour. mRNA was extracted from frontal cortex and hybridised to Illumina microarrays. Combined contrast analysis was used to identify genes showing different patterns of up- and down-regulation across the 4 models. 1823 genes were differentially regulated. They were over-represented in gene ontology categories of metabolism, protein handling and synapse. In each model compared to wild-type mice of the same genetic background, a number of genes showed increased expression changes of >10%, other genes showed decreases in each model. Most of the genes showed mixed effects. Several previous array findings were replicated. The results point to cellular stress and changes in post-synaptic remodelling as final common mechanisms of depression and resilience. PMID:21030216

  2. CREB5 computational regulation network construction and analysis between frontal cortex of HIV encephalitis (HIVE) and HIVE-control patients.

    PubMed

    Wang, Lin; Huang, Juxiang; Jiang, Minghu

    2011-07-01

    CREB5 computational regulation network construction and analysis of frontal cortex of HIV encephalitis (HIVE) is very useful to identify novel markers and potential targets for prognosis and therapy. By integration of gene regulatory network infer and the database for annotation, visualization and integrated discovery we identified and constructed significant molecule CREB5 regulation network from 12 frontal cortex of HIVE-control patients and 16 HIVE in the same GEO Dataset GDS1726. Our result verified CREB5 biological regulation module in the upstream of frontal cortex of HIVE-control patients (MAPKAPK3 activation; DGKG, LY96, TNFRSF11B inhibition) and downstream (ATP6V0E1, CFB, DGKG, MX1, TGFBR3 activation; LGALS3BP, RASGRP3, RDX, STAT1 inhibition), whereas in the upstream of frontal cortex of HIVE (BST2, CFB, LCAT, TNFRSF11B activation; CFHR1, LY96 inhibition) and downstream (GAS1, LCAT, LGALS3BP, NFAT5, VEZF1, ZNF652 activation; DGKG, IFITM1, LY96, TNFRSF11B inhibition). Importantly, we datamined that CREB5 regulation cluster of HIVE was involved in inflammatory response, proteolysis, biological adhesion, and negative regulation of biological process (only in HIVE terms) without positive regulation of cellular process, phosphotransferase, kinase, post-translational protein modification, ATP binding, transmembrane protein, calcium ion binding, acetylation, and hydrolase activity (only in HIVE-control patients terms), the condition was vital to inflammation and cognition impairment of HIVE. Our result demonstrated that common terms in both HIVE-control patients and HIVE included biological regulation, phosphoprotein, metabolic process, zinc, biosynthetic process, organelle, signal transduction, defense response, membrane, secreted, signal peptide, and glycoprotein, and these terms were more relative to inflammation and cognition impairment, therefore we deduced the stronger CREB5 regulation network in HIVE consistent with our number computation. It would be

  3. Dissociable contribution of the parietal and frontal cortex to coding movement direction and amplitude

    PubMed Central

    Davare, Marco; Zénon, Alexandre; Desmurget, Michel; Olivier, Etienne

    2015-01-01

    To reach for an object, we must convert its spatial location into an appropriate motor command, merging movement direction and amplitude. In humans, it has been suggested that this visuo-motor transformation occurs in a dorsomedial parieto-frontal pathway, although the causal contribution of the areas constituting the “reaching circuit” remains unknown. Here we used transcranial magnetic stimulation (TMS) in healthy volunteers to disrupt the function of either the medial intraparietal area (mIPS) or dorsal premotor cortex (PMd), in each hemisphere. The task consisted in performing step-tracking movements with the right wrist towards targets located in different directions and eccentricities; targets were either visible for the whole trial (Target-ON) or flashed for 200 ms (Target-OFF). Left and right mIPS disruption led to errors in the initial direction of movements performed towards contralateral targets. These errors were corrected online in the Target-ON condition but when the target was flashed for 200 ms, mIPS TMS manifested as a larger endpoint spreading. In contrast, left PMd virtual lesions led to higher acceleration and velocity peaks—two parameters typically used to probe the planned movement amplitude—irrespective of the target position, hemifield and presentation condition; in the Target-OFF condition, left PMd TMS induced overshooting and increased the endpoint dispersion along the axis of the target direction. These results indicate that left PMd intervenes in coding amplitude during movement preparation. The critical TMS timings leading to errors in direction and amplitude were different, namely 160–100 ms before movement onset for mIPS and 100–40 ms for left PMd. TMS applied over right PMd had no significant effect. These results demonstrate that, during motor preparation, direction and amplitude of goal-directed movements are processed by different cortical areas, at distinct timings, and according to a specific hemispheric

  4. Pharmacokinetic–pharmacodynamic modelling of fluvoxamine 5-HT transporter occupancy in rat frontal cortex

    PubMed Central

    Geldof, M; Freijer, J I; van Beijsterveldt, L; Langlois, X; Danhof, M

    2008-01-01

    Background and purpose: The pharmacokinetic–pharmacodynamic (PK–PD) correlation of fluvoxamine 5-HT transporter (SERT) occupancy was determined in rat frontal cortex ex vivo. Experimental approach: Rats (n=47) with permanent arterial and venous cannulas received a 30 min intravenous infusion of fluvoxamine (1 or 7.3 mg kg−1). At various time points after dosing, brains were collected for determination of fluvoxamine concentration and SERT occupancy. In addition, the time course of fluvoxamine concentration in plasma was determined up to the time of brain collection. In a separate study (n=26), the time course of fluvoxamine concentration in brain extracellular fluid (ECF) and plasma was determined. The results of the investigations were interpreted by nonlinear mixed effects modeling Key results: Highest SERT occupancy was reached at the first time point (10 or 15 min) and maintained for 1.5 and 7 h after 1 and 7.3 mg kg−1, respectively. Thereafter, SERT occupancy decreased linearly at a rate of 8% h−1. SERT occupancy could be directly related to plasma, brain ECF and brain tissue concentrations by a hyperbolic function (Bmax model). Maximal SERT occupancy (Bmax) was 95%. Estimated concentrations at half-maximal SERT occupancy (EC50) in plasma, ECF and brain tissue were 0.48, 0.22 and 14.8 ng mL−1 respectively. The minimum value of the objective function decreased 12 points for ECF and brain tissue concentrations relative to plasma (P<0.01), presumably as a result of nonlinear brain distribution. Conclusions and implications: The proposed PK–PD model constitutes a useful basis for prediction of the time course of ex vivo SERT occupancy in behavioural studies with selective serotonin reuptake inhibitors. PMID:18493251

  5. Frontal association cortex is engaged in stimulus integration during associative learning.

    PubMed

    Nakayama, Daisuke; Baraki, Zohal; Onoue, Kousuke; Ikegaya, Yuji; Matsuki, Norio; Nomura, Hiroshi

    2015-01-01

    The frontal association cortex (FrA) is implicated in higher brain function. Aberrant FrA activity is likely to be involved in dementia pathology. However, the functional circuits both within the FrA and with other regions are unclear. A recent study showed that inactivation of the FrA impairs memory consolidation of an auditory fear conditioning in young mice. In addition, dendritic spine remodeling of FrA neurons is sensitive to paired sensory stimuli that produce associative memory. These findings suggest that the FrA is engaged in neural processes critical to associative learning. Here we characterize stimulus integration in the mouse FrA during associative learning. We experimentally separated contextual fear conditioning into context exposure and shock, and found that memory formation requires protein synthesis associated with both context exposure and shock in the FrA. Both context exposure and shock trigger Arc, an activity-dependent immediate-early gene, expression in the FrA, and a subset of FrA neurons was dually activated by both stimuli. In addition, we found that the FrA receives projections from the perirhinal (PRh) and insular (IC) cortices and basolateral amygdala (BLA), which are implicated in context and shock encoding. PRh and IC neurons projecting to the FrA were activated by context exposure and shock, respectively. Arc expression in the FrA associated with context exposure and shock depended on PRh activity and both IC and BLA activities, respectively. These findings indicate that the FrA is engaged in stimulus integration and contributes to memory formation in associative learning. PMID:25496961

  6. Transcranial Direct Current Stimulation of Frontal Cortex Decreases Performance on the WAIS-IV Intelligence Test

    PubMed Central

    Sellers, Kristin K.; Mellin, Juliann M.; Lustenberger, Caroline M.; Boyle, Michael R.; Lee, Won Hee; Peterchev, Angel V.; Frohlich, Flavio

    2015-01-01

    Transcranial direct current stimulation (tDCS) modulates excitability of motor cortex. However, there is conflicting evidence about the efficacy of this non-invasive brain stimulation modality to modulate performance on cognitive tasks. Previous work has tested the effect of tDCS on specific facets of cognition and executive processing. However, no randomized, double-blind, sham-controlled study has looked at the effects of tDCS on a comprehensive battery of cognitive processes. The objective of this study was to test if tDCS had an effect on performance on a comprehensive assay of cognitive processes, a standardized intelligence quotient (IQ) test. The study consisted of two substudies and followed a double-blind, between-subjects, sham-controlled design. In total, 41 healthy adult participants completed the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV) as a baseline measure. At least one week later, participants in substudy 1 received either bilateral tDCS (anodes over both F4 and F3, cathode over Cz, 2mA at each anode for 20 minutes) or active sham tDCS (2mA for 40 seconds), and participants in substudy 2 received either right or left tDCS (anode over either F4 or F3, cathode over Cz, 2mA for 20 minutes). In both studies, the WAIS-IV was immediately administered following stimulation to assess for performance differences induced by bilateral and unilateral tDCS. Compared to sham stimulation, right, left, and bilateral tDCS reduced improvement between sessions on Full Scale IQ and the Perceptual Reasoning Index. This demonstration that frontal tDCS selectively degraded improvement on specific metrics of the WAIS-IV raises important questions about the often proposed role of tDCS in cognitive enhancement. PMID:25934490

  7. Expression of BDNF and TrkB Phosphorylation in the Rat Frontal Cortex During Morphine Withdrawal are NO Dependent.

    PubMed

    Peregud, Danil I; Yakovlev, Alexander A; Stepanichev, Mikhail Yu; Onufriev, Mikhail V; Panchenko, Leonid F; Gulyaeva, Natalia V

    2016-08-01

    Nitric oxide (NO) mediates pharmacological effects of opiates including dependence and abstinence. Modulation of NO synthesis during the induction phase of morphine dependence affects manifestations of morphine withdrawal syndrome, though little is known about mechanisms underlying this phenomenon. Neurotrophic and growth factors are involved in neuronal adaptation during opiate dependence. NO-dependent modulation of morphine dependence may be mediated by changes in expression and activity of neurotrophic and/or growth factors in the brain. Here, we studied the effects of NO synthesis inhibition during the induction phase of morphine dependence on the expression of brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and insulin-like growth factor 1 (IGF1) as well as their receptors in rat brain regions after spontaneous morphine withdrawal in dependent animals. Morphine dependence in rats was induced within 6 days by 12 injections of morphine in increasing doses (10-100 mg/kg), and NO synthase inhibitor L-N(G)-nitroarginine methyl ester (L-NAME) (10 mg/kg) was given 1 h before each morphine injection. The expression of the BDNF, GDNF, NGF, IGF1, and their receptors in the frontal cortex, striatum, hippocampus, and midbrain was assessed 40 h after morphine withdrawal. L-NAME treatment during morphine intoxication resulted in an aggravation of the spontaneous morphine withdrawal severity. Morphine withdrawal was accompanied by upregulation of BDNF, IGF1, and their receptors TrkB and IGF1R, respectively, on the mRNA level in the frontal cortex, and only BDNF in hippocampus and midbrain. L-NAME administration during morphine intoxication decreased abstinence-induced upregulation of these mRNAs in the frontal cortex, hippocampus and midbrain. L-NAME prevented from abstinence-induced elevation of mature but not pro-form of BDNF polypeptide in the frontal cortex. While morphine abstinence did not affect Trk

  8. Induction of hyperphagia and carbohydrate intake by mu-opioid receptor stimulation in circumscribed regions of frontal cortex

    PubMed Central

    Mena, Jesus D.; Sadeghian, Ken; Baldo, Brian A.

    2011-01-01

    Frontal cortical regions are activated by food-associated stimuli, and this activation appears to be dysregulated in individuals with eating disorders. Nevertheless, frontal control of basic unconditioned feeding responses remains poorly understood. Here we show that hyperphagia can be driven by μ-opioid receptor stimulation in restricted regions of ventral medial prefrontal cortex (vmPFC) and orbitofrontal cortex. In both ad libitum-fed and food-restricted male Sprague-Dawley rats, bilateral infusions of the μ-opioid agonist, DAMGO, markedly increased intake of standard rat chow. When given a choice between palatable fat- versus carbohydrate enriched test diets, intra-vmPFC DAMGO infusions selectively increased carbohydrate intake, even in rats with a baseline fat preference. Rats also exhibited motor hyperactivity characterized by rapid switching between brief bouts of investigatory and ingestive behaviors. Intra-vmPFC DAMGO affected neither water intake nor non-specific oral behavior. Similar DAMGO infusions into neighboring areas of lateral orbital or anterior motor cortex had minimal effects on feeding. Neither stimulation of vmPFC-localized delta-opioid, kappa-opioid, dopaminergic, serotonergic, or noradrenergic receptors, nor antagonism of D1, 5HT1A, or alpha- or beta-adrenoceptors, reproduced the profile of DAMGO effects. Muscimol-mediated inactivation of the vmPFC, and intra-vmPFC stimulation of κ-opioid receptors or blockade of 5HT2A receptors, suppressed motor activity and increased feeding bout duration-a profile opposite to that seen with DAMGO. Hence, μ-opioid-induced hyperphagia and carbohydrate intake can be elicited with remarkable pharmacological and behavioral specificity from discrete subterritories of the frontal cortex. These findings may have implications for understanding affect-driven feeding and loss of restraint in eating disorders. PMID:21368037

  9. Glutamate receptor binding in the frontal cortex and dorsal striatum of aged rats with impaired attentional set-shifting.

    PubMed

    Nicolle, Michelle M; Baxter, Mark G

    2003-12-01

    Aged Long-Evans rats exhibit deficits in attentional set shifting, an aspect of executive function, relative to adult rats. Impairments in set shifting and spatial learning are uncorrelated in aged rats, indicating a possible dissociation of the effects of ageing in prefrontal versus hippocampal systems. Ionotropic glutamate receptor binding was assessed using an in vitro autoradiography method in young and aged rats. The rats had been tested on a set-shifting task that measured attentional set shifts and reversal learning, as well as in a spatial learning task in the Morris water maze. [3H]Kainate, [3H]AMPA and NMDA-displaceable [3H]glutamate receptor binding were quantified in orbital cortex, cingulate cortex, medial frontal cortex, dorsolateral and dorsomedial striatum. Age-related decreases in [3H]kainate binding were apparent in all regions measured. Similarly, NMDA-displaceable [3H]glutamate binding was decreased in the aged rats in all the regions measured except for the medial frontal area where no age effects were observed. [3H]AMPA receptor binding was preserved with age in all the regions measured. Lower levels of [3H]kainate binding in the cingulate cortex were significantly correlated with poorer set-shifting performance, whereas higher levels of NMDA binding in the dorsomedial striatum were correlated with poorer set-shifting performance. There were no significant correlations between the levels of ionotropic glutamate receptors and performance in the reversal task or spatial learning in the Morris water maze. These results indicate that age-related behavioural deficits in attentional set shifting are selectively associated with neurobiological alterations in the cingulate cortex and dorsomedial striatum. PMID:14686906

  10. Rank Signals in Four Areas of Macaque Frontal Cortex During Selection of Actions and Objects in Serial Order

    PubMed Central

    Olson, Carl R.

    2010-01-01

    Neurons in several areas of monkey frontal cortex exhibit ordinal position (rank) selectivity during the performance of serial order tasks. It has been unclear whether rank selectivity or the dependence of rank selectivity on task context varies across the areas of frontal cortex. To resolve this issue, we recorded from neurons in the supplementary motor area (SMA), presupplementary motor area (pre-SMA), supplementary eye field (SEF), and dorsolateral prefrontal cortex (dlPFC) as monkeys performed two oculomotor tasks, one requiring the selection of three actions in sequence and the other requiring the selection of three objects in sequence. We found that neurons representing all ranks were present in all areas. Only to a moderate degree did the prevalence and nature of rank selectivity vary from area to area. The two most prominent inter-area differences involved a lower prevalence of rank selectivity in the dlPFC than in the other areas and a higher proportion of neurons preferring late ranks in the SMA and SEF than in the other areas. Neurons in all four areas are rank generalists in the sense of favoring the same rank in both the serial action task and the serial object task. PMID:20445037

  11. Long-range orbitofrontal and amygdala axons show divergent patterns of maturation in the frontal cortex across adolescence.

    PubMed

    Johnson, Carolyn M; Loucks, F Alexandra; Peckler, Hannah; Thomas, A Wren; Janak, Patricia H; Wilbrecht, Linda

    2016-04-01

    The adolescent transition from juvenile to adult is marked by anatomical and functional remodeling of brain networks. Currently, the cellular and synaptic level changes underlying the adolescent transition are only coarsely understood. Here, we use two-photon imaging to make time-lapse observations of long-range axons that innervate the frontal cortex in the living brain. We labeled cells in the orbitofrontal cortex (OFC) and basolateral amygdala (BLA) and imaged their axonal afferents to the dorsomedial prefrontal cortex (dmPFC). We also imaged the apical dendrites of dmPFC pyramidal neurons. Images were taken daily in separate cohorts of juvenile (P24-P28) and young adult mice (P64-P68), ages where we have previously discovered differences in dmPFC dependent decision-making. Dendritic spines were pruned across this peri-adolescent period, while BLA and OFC afferents followed alternate developmental trajectories. OFC boutons showed no decrease in density, but did show a decrease in daily bouton gain and loss with age. BLA axons showed an increase in both bouton density and daily bouton gain at the later age, suggesting a delayed window of enhanced plasticity. Our findings reveal projection specific maturation of synaptic structures within a single frontal region and suggest that stabilization is a more general characteristic of maturation than pruning. PMID:26896859

  12. Downregulation of GABA[Subscript A] Receptor Protein Subunits a6, ß2, d, e, ?2, ?, and ?2 in Superior Frontal Cortex of Subjects with Autism

    ERIC Educational Resources Information Center

    Fatemi, S. Hossein; Reutiman, Teri J.; Folsom, Timothy D.; Rustan, Oyvind G.; Rooney, Robert J.; Thuras, Paul D.

    2014-01-01

    We measured protein and mRNA levels for nine gamma-aminobutyric acid A (GABA[subscript A]) receptor subunits in three brain regions (cerebellum, superior frontal cortex, and parietal cortex) in subjects with autism versus matched controls. We observed changes in mRNA for a number of GABA[subscript A] and GABA[subscript B] subunits and overall…

  13. Issues in localization of brain function: The case of lateralized frontal cortex in cognition, emotion, and psychopathology

    PubMed Central

    Miller, Gregory A.; Crocker, Laura D.; Spielberg, Jeffrey M.; Infantolino, Zachary P.; Heller, Wendy

    2013-01-01

    The appeal of simple, sweeping portraits of large-scale brain mechanisms relevant to psychological phenomena competes with a rich, complex research base. As a prominent example, two views of frontal brain organization have emphasized dichotomous lateralization as a function of either emotional valence (positive/negative) or approach/avoidance motivation. Compelling findings support each. The literature has struggled to choose between them for three decades, without success. Both views are proving untenable as comprehensive models. Evidence of other frontal lateralizations, involving distinctions among dimensions of depression and anxiety, make a dichotomous view even more problematic. Recent evidence indicates that positive valence and approach motivation are associated with different areas in the left-hemisphere. Findings that appear contradictory at the level of frontal lobes as the units of analysis can be accommodated because hemodynamic and electromagnetic neuroimaging studies suggest considerable functional differentiation, in specialization and activation, of subregions of frontal cortex, including their connectivity to each other and to other regions. Such findings contribute to a more nuanced understanding of functional localization that accommodates aspects of multiple theoretical perspectives. PMID:23386814

  14. Mechanistic model for the acute effect of fluvoxamine on 5-HT and 5-HIAA concentrations in rat frontal cortex.

    PubMed

    Geldof, Marian; Freijer, Jan I; Peletier, Lambertus A; van Beijsterveldt, Ludy; Danhof, Meindert

    2008-03-01

    A mechanistic model is proposed to predict the time course of the concentrations of 5-HT and its metabolite 5-hydroxyindolacetic acid (5-HIAA) in rat frontal cortex following acute administration of SSRIs. In the model, SSRIs increase synaptic 5-HT concentrations by reversible blockade of the SERT in a direct concentration-dependent manner, while the 5-HT response is attenuated by negative feedback via 5-HT autoreceptors. In principle, the model allows for the description of oscillatory patterns in the time course of 5-HT and 5-HIAA concentrations in brain extracellular fluid. The model was applied in a pharmacokinetic-pharmacodynamic (PK/PD) investigation on the time course of the microdialysate 5-HT and 5-HIAA response in rat frontal cortex following a 30-min intravenous infusion of 3.7 and 7.3mg/kg fluvoxamine. Directly after administration of fluvoxamine, concentrations of 5-HT were increased to approximately 450-600% of baseline values while 5-HIAA concentrations were decreased. Thereafter 5-HT and 5-HIAA concentrations gradually returned to baseline values in 6-10h, respectively. The PK/PD analysis revealed that inhibition of 5-HT reuptake was directly related to the fluvoxamine concentration in plasma, with 50% inhibition of 5-HT reuptake occurring at a plasma concentration of 1.1ng/ml (EC50). The levels of 5-HT at which 50% of the inhibition of the 5-HT response was reached (IC50) amounted to 272% of baseline. The model was unable to capture the oscillatory patterns in the individual concentration time curves, which appeared to occur randomly. The proposed mechanistic model is the first step in modeling of complex neurotransmission processes. The model constitutes a useful basis for prediction of the time course of median 5-HT and 5-HIAA concentrations in the frontal cortex in behavioral pharmacology studies in vivo. PMID:18207708

  15. Observing accidental and intentional unusual actions is associated with different subregions of the medial frontal cortex.

    PubMed

    Desmet, Charlotte; Brass, Marcel

    2015-11-15

    The literature on action observation revealed contradictory results regarding the activation of different subregions of the medial prefrontal cortex when observing unusual behaviour. Error observation research has shown that the posterior part of the medial prefrontal cortex is more active when observing unusual behaviour compared to usual behaviour while action understanding research has revealed some mixed results concerning the role of the anterior part of the medial prefrontal cortex during the observation of unusual actions. Here, we resolve this discrepancy in the literature by showing that different parts of the medial prefrontal cortex are active depending on whether an observed unusual behaviour is intentional or not. While the posterior medial prefrontal cortex is more active when we observe unusual accidental actions compared to unusual intentional actions, a more anterior part of the medial prefrontal cortex is more active when we observe unusual intentional actions compared to unusual accidental actions. PMID:26279209

  16. Increased activity in frontal motor cortex compensates impaired speech perception in older adults

    PubMed Central

    Du, Yi; Buchsbaum, Bradley R.; Grady, Cheryl L.; Alain, Claude

    2016-01-01

    Understanding speech in noisy environments is challenging, especially for seniors. Although evidence suggests that older adults increasingly recruit prefrontal cortices to offset reduced periphery and central auditory processing, the brain mechanisms underlying such compensation remain elusive. Here we show that relative to young adults, older adults show higher activation of frontal speech motor areas as measured by functional MRI during a syllable identification task at varying signal-to-noise ratios. This increased activity correlates with improved speech discrimination performance in older adults. Multivoxel pattern classification reveals that despite an overall phoneme dedifferentiation, older adults show greater specificity of phoneme representations in frontal articulatory regions than auditory regions. Moreover, older adults with stronger frontal activity have higher phoneme specificity in frontal and auditory regions. Thus, preserved phoneme specificity and upregulation of activity in speech motor regions provide a means of compensation in older adults for decoding impoverished speech representations in adverse listening conditions. PMID:27483187

  17. A hierarchy of timescales explains distinct effects of local inhibition of primary visual cortex and frontal eye fields.

    PubMed

    Cocchi, Luca; Sale, Martin V; L Gollo, Leonardo; Bell, Peter T; Nguyen, Vinh T; Zalesky, Andrew; Breakspear, Michael; Mattingley, Jason B

    2016-01-01

    Within the primate visual system, areas at lower levels of the cortical hierarchy process basic visual features, whereas those at higher levels, such as the frontal eye fields (FEF), are thought to modulate sensory processes via feedback connections. Despite these functional exchanges during perception, there is little shared activity between early and late visual regions at rest. How interactions emerge between regions encompassing distinct levels of the visual hierarchy remains unknown. Here we combined neuroimaging, non-invasive cortical stimulation and computational modelling to characterize changes in functional interactions across widespread neural networks before and after local inhibition of primary visual cortex or FEF. We found that stimulation of early visual cortex selectively increased feedforward interactions with FEF and extrastriate visual areas, whereas identical stimulation of the FEF decreased feedback interactions with early visual areas. Computational modelling suggests that these opposing effects reflect a fast-slow timescale hierarchy from sensory to association areas. PMID:27596931

  18. Time-varying covariance of neural activities recorded in striatum and frontal cortex as monkeys perform sequential-saccade tasks.

    PubMed

    Fujii, N; Graybiel, A M

    2005-06-21

    Cortico-basal ganglia circuits are key parts of the brain's habit system, but little is yet known about how these forebrain pathways function as ingrained habits are performed. We simultaneously recorded spike and local field potential (LFP) activity from regions of the frontal cortex and basal ganglia implicated in visuo-oculomotor control as highly trained macaque monkeys performed sequences of visually guided saccades. The tasks were repetitive, required no new learning, and could be performed nearly automatically. Our findings demonstrate striking differences between the relative timing of striatal and cortical activity during performance of the tasks. At the onset of the visual cues, LFPs in the prefrontal cortex and the oculomotor zone of the striatum showed near-synchronous activation. During the period of sequential-saccade performance, however, peak LFP activity occurred 100-300 msec later in the striatum than in the prefrontal cortex. Peak prefrontal activity tended to be peri-saccadic, whereas peak striatal activity tended to be post-saccadic. This temporal offset was also apparent in pairs of simultaneously recorded prefrontal and striatal neurons. In triple-site recordings, the LFP activity recorded in the supplementary eye field shared temporal characteristics of both the prefrontal and the striatal patterns. The near simultaneity of prefrontal and striatal peak responses at cue onsets, but temporal lag of striatal activity in the movement periods, suggests that the striatum may integrate corollary discharge or confirmatory response signals during sequential task performance. These timing relationships may be signatures of the normal functioning of striatal and frontal cortex during repetitive performance of learned behaviors. PMID:15956185

  19. Time-varying covariance of neural activities recorded in striatum and frontal cortex as monkeys perform sequential-saccade tasks

    PubMed Central

    Fujii, N.; Graybiel, A. M.

    2005-01-01

    Cortico-basal ganglia circuits are key parts of the brain's habit system, but little is yet known about how these forebrain pathways function as ingrained habits are performed. We simultaneously recorded spike and local field potential (LFP) activity from regions of the frontal cortex and basal ganglia implicated in visuo-oculomotor control as highly trained macaque monkeys performed sequences of visually guided saccades. The tasks were repetitive, required no new learning, and could be performed nearly automatically. Our findings demonstrate striking differences between the relative timing of striatal and cortical activity during performance of the tasks. At the onset of the visual cues, LFPs in the prefrontal cortex and the oculomotor zone of the striatum showed near-synchronous activation. During the period of sequential-saccade performance, however, peak LFP activity occurred 100–300 msec later in the striatum than in the prefrontal cortex. Peak prefrontal activity tended to be peri-saccadic, whereas peak striatal activity tended to be post-saccadic. This temporal offset was also apparent in pairs of simultaneously recorded prefrontal and striatal neurons. In triple-site recordings, the LFP activity recorded in the supplementary eye field shared temporal characteristics of both the prefrontal and the striatal patterns. The near simultaneity of prefrontal and striatal peak responses at cue onsets, but temporal lag of striatal activity in the movement periods, suggests that the striatum may integrate corollary discharge or confirmatory response signals during sequential task performance. These timing relationships may be signatures of the normal functioning of striatal and frontal cortex during repetitive performance of learned behaviors. PMID:15956185

  20. Ginsenoside rb1 modulates level of monoamine neurotransmitters in mice frontal cortex and cerebellum in response to immobilization stress.

    PubMed

    Lee, Sang Hee; Hur, Jinyoung; Lee, Eunjoo H; Kim, Sun Yeou

    2012-09-01

    Cerebral monoamines play important roles as neurotransmitters that are associated with various stressful stimuli. Some components such as ginsenosides (triterpenoidal glycosides derived from the Ginseng Radix) may interact with monoamine systems. The aim of this study was to determine whether ginsenoside Rb1 can modulate levels of the monoamines such as dihydroxyphenylalanine (DOPA), dopamine (DA), norepinephrine (NE), epinephrine (EP), 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydorxytryptamine (5-HT), 5-hydroxindole-3-acetic acid (5-HIAA), and 5-hydroxytryptophan (5-HTP) in mice frontal cortex and cerebellum in response to immobilization stress. Mice were treated with ginsenoside Rb1 (10 mg/kg, oral) before a single 30 min immobilization stress. Acute immobilization stress resulted in elevation of monoamine levels in frontal cortex and cerebellum. Pretreatment with ginsenoside Rb1 attenuated the stress-induced changes in the levels of monoamines in each region. The present findings showed the anti-stress potential of ginsenoside Rb1 in relation to regulation effects on the cerebral monoaminergic systems. Therefore, the ginsenoside Rb1 may be a useful candidate for treating several brain symptoms related with stress. PMID:24009838

  1. Prenatal Stress Enhances Excitatory Synaptic Transmission and Impairs Long-Term Potentiation in the Frontal Cortex of Adult Offspring Rats

    PubMed Central

    Sowa, Joanna; Bobula, Bartosz; Glombik, Katarzyna; Slusarczyk, Joanna; Basta-Kaim, Agnieszka; Hess, Grzegorz

    2015-01-01

    The effects of prenatal stress procedure were investigated in 3 months old male rats. Prenatally stressed rats showed depressive-like behavior in the forced swim test, including increased immobility, decreased mobility and decreased climbing. In ex vivo frontal cortex slices originating from prenatally stressed animals, the amplitude of extracellular field potentials (FPs) recorded in cortical layer II/III was larger, and the mean amplitude ratio of pharmacologically-isolated NMDA to the AMPA/kainate component of the field potential—smaller than in control preparations. Prenatal stress also resulted in a reduced magnitude of long-term potentiation (LTP). These effects were accompanied by an increase in the mean frequency, but not the mean amplitude, of spontaneous excitatory postsynaptic currents (sEPSCs) in layer II/III pyramidal neurons. These data demonstrate that stress during pregnancy may lead not only to behavioral disturbances, but also impairs the glutamatergic transmission and long-term synaptic plasticity in the frontal cortex of the adult offspring. PMID:25749097

  2. Anterior and posterior subareas of the dorsolateral frontal cortex in socially relevant decisions based on masked affect expressions

    PubMed Central

    Prochnow, Denise; Brunheim, Sascha; Kossack, Hannes; Eickhoff, Simon B.; Markowitsch, Hans J.; Seitz, Rüdiger J.

    2015-01-01

    Socially-relevant decisions are based on clearly recognizable but also not consciously accessible affective stimuli. We studied the role of the dorsolateral frontal cortex (DLFC) in decision-making on masked affect expressions using functional magnetic resonance imaging. Our paradigm permitted us to capture brain activity during a pre-decision phase when the subjects viewed emotional expressions below the threshold of subjective awareness, and during the decision phase, which was based on verbal descriptions as the choice criterion. Using meta-analytic connectivity modeling, we found that the preparatory phase of the decision was associated with activity in a right-posterior portion of the DLFC featuring co-activations in the left-inferior frontal cortex. During the subsequent decision a right-anterior and more dorsal portion of the DLFC became activated, exhibiting a different co-activation pattern. These results provide evidence for partially independent sub-regions within the DLFC, supporting the notion of dual associative processes in intuitive judgments. PMID:26236464

  3. Impaired spatial working memory and decreased frontal cortex BDNF protein level in dopamine transporter knock out mice

    PubMed Central

    Li, BingJin; Arime, Yosefu; Hall, F. Scott; Uhl, George R.; Sora, Ichiro

    2010-01-01

    Brain-derived neurotrophic factor (BDNF), one of the key brain neurotrophins, has been implicated in neuronal plasticity and memory. Recent studies document the importance of BDNF for normal long-term memory functions. However, there are few studies of the roles of BDNF in short term memory. Dopamine is likely to play important roles in BDNF gene expression in specific brain regions, including frontal cortical regions that are implicated in short term working memory processes that include spontaneous alternation. We have thus tested spatial working memory in dopamine transporter knockout (DAT KO) and wild-type mice. Spontaneous alternation in the Y-maze, an index of short-term spatial working memory in mice, was significantly decreased in DAT KO mice compared to wildtype mice. BDNF protein was significantly decreased in frontal cortex, though not in striatum or hippocampus, of the DAT KO mice. The data support the hypothesis that impaired spatial working memory in DAT KO mice may be related to decreased frontal cortical BDNF in these animals, and document apparent roles for BDNF in a short term memory process. PMID:19932884

  4. Infusion of D1 Dopamine Receptor Agonist into Medial Frontal Cortex Disrupts Neural Correlates of Interval Timing

    PubMed Central

    Parker, Krystal L.; Ruggiero, Rafael N.; Narayanan, Nandakumar S.

    2015-01-01

    Medial frontal cortical (MFC) dopamine is essential for the organization of behavior in time. Our prior work indicates that blocking D1 dopamine receptors (D1DR) attenuates temporal processing and low-frequency oscillations by MFC neuronal networks. Here we investigate the effects of focal infusion of the D1DR agonist SKF82958 into MFC during interval timing. MFC D1DR agonist infusion impaired interval timing performance without changing overall firing rates of MFC neurons. MFC ramping patterns of neuronal activity that reflect temporal processing were attenuated following infusion of MFC D1DR agonist. MFC D1DR agonist infusion also altered MFC field potentials by enhancing delta activity between 1 and 4 Hz and attenuating alpha activity between 8 and 15 Hz. These data support the idea that the influence of D1-dopamine signals on frontal neuronal activity adheres to a U-shaped curve, and that cognition requires optimal levels of dopamine in frontal cortex. PMID:26617499

  5. Manic episodes are related to changes in frontal cortex: a longitudinal neuroimaging study of bipolar disorder 1.

    PubMed

    Abé, Christoph; Ekman, Carl-Johan; Sellgren, Carl; Petrovic, Predrag; Ingvar, Martin; Landén, Mikael

    2015-11-01

    Higher numbers of manic episodes in bipolar patients has, in cross-sectional studies, been associated with less grey matter volume in prefrontal brain areas. Longitudinal studies are needed to determine if manic episodes set off progressive cortical changes, or if the association is better explained by premorbid brain conditions that increase risk for mania. We followed patients with bipolar disorder type 1 for 6 years. Structural brain magnetic resonance imaging scans were performed at baseline and follow-up. We compared patients who had at least one manic episode between baseline and follow-up (Mania group, n = 13) with those who had no manic episodes (No-Mania group, n = 18). We used measures of cortical volume, thickness, and area to assess grey matter changes between baseline and follow-up. We found significantly decreased frontal cortical volume (dorsolateral prefrontal and inferior frontal cortex) in the Mania group, but no volume changes in the No-Mania group. Our results indicate that volume decrease in frontal brain regions can be attributed to the incidence of manic episodes. PMID:26373602

  6. Social and emotional functions in three patients with medial frontal lobe damage including the anterior cingulate cortex

    PubMed Central

    Baird, Amee; Dewar, Bonnie-Kate; Critchley, Hugo; Dolan, Ray; Shallice, Tim; Cipolotti, Lisa

    2009-01-01

    Introduction The aim of this study was to explore social and emotional functions in patients with medial frontal damage including the anterior cingulate cortex (ACC). Methods Three patients with medial frontal lobe lesions primarily involving the ACC performed tasks on motivational decision making, emotional facial expression recognition, and social cognition, including theory of mind (ToM). Their performance on these tasks was compared with age and education matched healthy controls. Results Patient performance on the motivational decision making and social situations tasks did not differ from controls. Selective emotional facial expression recognition impairment for fear was evident in one patient with a unilateral right ACC lesion (patient 3). ToM impairment was present in only one patient with a bilateral ACC lesion (patient 2). In contrast, the two patients with unilateral right ACC lesions had intact ToM (patients 1 and 3). Conclusions These findings suggest that medial frontal lobe lesions primarily involving the ACC do not appear to critically disrupt motivational decision making or social situation processing. The ACC plays a role in processing particular types of emotion (fear). Bilateral ACC damage impairs ToM processing, but unilateral damage to the right ACC is not sufficient to disrupt ToM. PMID:17354076

  7. Left Inferior Frontal Cortex and Syntax: Function, Structure and Behaviour in Patients with Left Hemisphere Damage

    ERIC Educational Resources Information Center

    Tyler, Lorraine K.; Marslen-Wilson, William D.; Randall, Billi; Wright, Paul; Devereux, Barry J.; Zhuang, Jie; Papoutsi, Marina; Stamatakis, Emmanuel A.

    2011-01-01

    For the past 150 years, neurobiological models of language have debated the role of key brain regions in language function. One consistently debated set of issues concern the role of the left inferior frontal gyrus in syntactic processing. Here we combine measures of functional activity, grey matter integrity and performance in patients with left…

  8. Agrammatic Comprehension Caused by a Glioma in the Left Frontal Cortex

    ERIC Educational Resources Information Center

    Kinno, Ryuta; Muragaki, Yoshihiro; Hori, Tomokatsu; Maruyama, Takashi; Kawamura, Mitsuru; Sakai, Kuniyoshi L.

    2009-01-01

    It has been known that lesions in the left inferior frontal gyrus (L. IFG) do not always cause Broca's aphasia, casting doubt upon the specificity of this region. We have previously devised a picture-sentence matching task for a functional magnetic resonance imaging (fMRI) study, and observed that both pars triangularis (L. F3t) of L. IFG…

  9. The role of left inferior frontal cortex during audiovisual speech perception in infants.

    PubMed

    Altvater-Mackensen, Nicole; Grossmann, Tobias

    2016-06-01

    In the first year of life, infants' speech perception attunes to their native language. While the behavioral changes associated with native language attunement are fairly well mapped, the underlying mechanisms and neural processes are still only poorly understood. Using fNIRS and eye tracking, the current study investigated 6-month-old infants' processing of audiovisual speech that contained matching or mismatching auditory and visual speech cues. Our results revealed that infants' speech-sensitive brain responses in inferior frontal brain regions were lateralized to the left hemisphere. Critically, our results further revealed that speech-sensitive left inferior frontal regions showed enhanced responses to matching when compared to mismatching audiovisual speech, and that infants with a preference to look at the speaker's mouth showed an enhanced left inferior frontal response to speech compared to infants with a preference to look at the speaker's eyes. These results suggest that left inferior frontal regions play a crucial role in associating information from different modalities during native language attunement, fostering the formation of multimodal phonological categories. PMID:26946090

  10. Reduced functional connectivity to the frontal cortex during processing of social cues in autism spectrum disorder.

    PubMed

    Hoffmann, Elgin; Brück, Carolin; Kreifelts, Benjamin; Ethofer, Thomas; Wildgruber, Dirk

    2016-08-01

    People diagnosed with autism spectrum disorder (ASD) characteristically present with severe difficulties in interpreting every-day social signals. Currently it is assumed that these difficulties might have neurobiological correlates in alterations in activation as well as in connectivity in and between regions of the social perception network suggested to govern the processing of social cues. In this study, we conducted functional magnetic resonance imaging (fMRI)-based activation and connectivity analyses focusing on face-, voice-, and audiovisual-processing brain regions as the most important subareas of the social perception network. Results revealed alterations in connectivity among regions involved in the processing of social stimuli in ASD subjects compared to typically developed (TD) controls-specifically, a reduced connectivity between the left temporal voice area (TVA) and the superior and medial frontal gyrus. Alterations in connectivity, moreover, were correlated with the severity of autistic traits: correlation analysis indicated that the connectivity between the left TVA and the limbic lobe, anterior cingulate and the medial frontal gyrus as well as between the right TVA and the frontal lobe, anterior cingulate, limbic lobe and the caudate decreased with increasing symptom severity. As these frontal regions are understood to play an important role in interpreting and mentalizing social signals, the observed underconnectivity might be construed as playing a role in social impairments in ASD. PMID:27094176

  11. The contribution of distinct subregions of the ventromedial frontal cortex to emotion, social behavior, and decision making.

    PubMed

    Rudebeck, P H; Bannerman, D M; Rushworth, M F S

    2008-12-01

    Damage to the ventromedial frontal cortex (VMFC) in humans is associated with deficits in decision making. Decision making, however, often happens while people are interacting with others, where it is important to take the social consequences of a course of action into account. It is well known that VMFC lesions also lead to marked alterations in patients' emotions and ability to interact socially; however, it has not been clear which parts of the VMFC are critical for these changes. Recently, there has been considerable interest in the role of the VMFC in choice behavior during interpersonal exchanges. Here, we highlight recent research that suggests that two areas within or adjacent to the VMFC, the orbitofrontal cortex (OFC) and the anterior cingulate cortex (ACC), may play distinct but complementary roles in mediating normal patterns of emotion and social behavior. Converging lines of evidence from human, macaque, and rat studies now suggest that the OFC may be more specialized for simple emotional responses, such as fear and aggression, through its role in representing primary reinforcement or punishment. By contrast, the ACC may play a distinct role in more complex aspects of emotion, such as social interaction, by virtue of its connections with the discrete parts of the temporal lobe and subcortical structures that control autonomic responses. PMID:19033243

  12. Differences in the mechanisms that increase noradrenaline efflux after administration of d-amphetamine: a dual-probe microdialysis study in rat frontal cortex and hypothalamus.

    PubMed

    Géranton, Sandrine M; Heal, David J; Stanford, S Clare

    2003-08-01

    1. The extent to which impulse-independent release of noradrenaline and/or inhibition of its reuptake contribute to the response to d-amphetamine in vivo is unclear. Here, dual-probe microdialysis was used to investigate this question in the rat frontal cortex and hypothalamus. 2. After systemic administration of d-amphetamine (10 mg kg(-1)), or its local infusion (10 micro M), the increase in noradrenaline efflux in the hypothalamus was greater than in the frontal cortex. 3. In contrast, during local infusion of the noradrenaline reuptake inhibitor, BTS 54 354 (50 micro M), the noradrenaline response was similar in the frontal cortex and hypothalamus, even after systemic administration of the alpha(2)-antagonist, atipamezole, to block presynaptic inhibition of transmitter release and neuronal firing. 4. In the frontal cortex, but not the hypothalamus, the noradrenaline response to 10 micro M d-amphetamine was constrained by activation of alpha(2)-adrenoceptors. This suggests that, at this concentration, inhibition of reuptake of noradrenaline, following its impulse-dependent release, is evident in the frontal cortex, but that the noradrenaline response in the hypothalamus derives mostly from impulse-independent release (retrotransport). 5. Atipamezole did not affect the noradrenaline response to 100 micro M d-amphetamine in either brain region possibly because, at this higher concentration, retrotransport of noradrenaline masks any compensatory reduction in impulse-evoked release. 6. It is concluded that inhibition of reuptake and retrotransport make different contributions to the noradrenaline response to d-amphetamine in the frontal cortex and hypothalamus and that retrotransport increases with the concentration of d-amphetamine. PMID:12922931

  13. Hidden prenatal malnutrition in the rat: role of β₁-adrenoceptors on synaptic plasticity in the frontal cortex.

    PubMed

    Flores, Osvaldo; Pérez, Hernán; Valladares, Luis; Morgan, Carlos; Gatica, Arnaldo; Burgos, Héctor; Olivares, Ricardo; Hernández, Alejandro

    2011-10-01

    Moderate reduction in the protein content of the mother's diet (hidden malnutrition) does not alter body and brain weights of rat pups at birth, but leads to dysfunction of neocortical noradrenaline systems together with impaired long-term potentiation and visuo-spatial memory performance. As β₁-adrenoceptors and downstream protein kinase signaling are critically involved in synaptic long-term potentiation and memory formation, we evaluated the β₁-adrenoceptor density and the expression of cyclic-AMP dependent protein kinase, calcium/calmodulin-dependent protein kinase and protein kinase Fyn, in the frontal cortex of prenatally malnourished adult rats. In addition, we also studied if β₁-adrenoceptor activation with the selective β₁ agonist dobutamine could improve deficits of prefrontal cortex long-term potentiation presenting these animals. Prenatally malnourished rats exhibited half of β₁-adrenoceptor binding, together with a 51% and 65% reduction of cyclic AMP-dependent protein kinase α and calcium/calmodulin-dependent protein kinase α expression, respectively, as compared with eutrophic animals. Administration of the selective β₁ agonist dobutamine prior to tetanization completely rescued the ability of the prefrontal cortex to develop and maintain long-term potentiation in the malnourished rats. Results suggest that under-expression of neocortical β₁-adrenoceptors and protein kinase signaling in hidden malnourished rats functionally affects the synaptic networks subserving prefrontal cortex long-term potentiation. β₁-adrenoceptor activation was sufficient to fully recover neocortical plasticity in the PKA- and calcium/calmodulin-dependent protein kinase II-deficient undernourished rats, possibly by producing extra amounts of cAMP and/or by recruiting alternative signaling cascades. PMID:21848869

  14. Connectivity reveals relationship of brain areas for reward-guided learning and decision making in human and monkey frontal cortex

    PubMed Central

    Neubert, Franz-Xaver; Mars, Rogier B.; Sallet, Jérôme; Rushworth, Matthew F. S.

    2015-01-01

    Reward-guided decision-making depends on a network of brain regions. Among these are the orbitofrontal and the anterior cingulate cortex. However, it is difficult to ascertain if these areas constitute anatomical and functional unities, and how these areas correspond between monkeys and humans. To address these questions we looked at connectivity profiles of these areas using resting-state functional MRI in 38 humans and 25 macaque monkeys. We sought brain regions in the macaque that resembled 10 human areas identified with decision making and brain regions in the human that resembled six macaque areas identified with decision making. We also used diffusion-weighted MRI to delineate key human orbital and medial frontal brain regions. We identified 21 different regions, many of which could be linked to particular aspects of reward-guided learning, valuation, and decision making, and in many cases we identified areas in the macaque with similar coupling profiles. PMID:25947150

  15. The role of the dorsal medial frontal cortex in central processing limitation: a transcranial magnetic stimulation study.

    PubMed

    Soutschek, Alexander; Taylor, Paul C J; Schubert, Torsten

    2016-09-01

    When humans perform two tasks simultaneously, responses to the second task are increasingly delayed as the interval between the two tasks decreases (psychological refractory period). This delay of the second task is thought to reflect a central processing limitation at the response selection stage. However, the neural mechanisms underlying this central processing limitation remain unclear. Using transcranial magnetic stimulation (TMS), we examined the role of the dorsal medial frontal cortex (dMFC) in a dual-task paradigm in which participants performed an auditory task 1 and a visual task 2. We found that dMFC TMS, relative to control conditions, reduced the psychological refractory period for task 2 processing, whereas we observed no dMFC TMS effects on task 1 processing. This suggests a causal role of the dMFC in coordinating response selection processes at the central bottleneck. PMID:27083589

  16. Spatially selective representations of voluntary and stimulus-driven attentional priority in human occipital, parietal, and frontal cortex.

    PubMed

    Serences, John T; Yantis, Steven

    2007-02-01

    When multiple objects are present in a visual scene, they compete for cortical processing in the visual system; selective attention biases this competition so that representations of behaviorally relevant objects enter awareness and irrelevant objects do not. Deployments of selective attention can be voluntary (e.g., shift or attention to a target's expected spatial location) or stimulus driven (e.g., capture of attention by a target-defining feature such as color). Here we use functional magnetic resonance imaging to show that both of these factors induce spatially selective attentional modulations within regions of human occipital, parietal, and frontal cortex. In addition, the voluntary attentional modulations are temporally sustained, indicating that activity in these regions dynamically tracks the locus of attention. These data show that a convolution of factors, including prior knowledge of location and target-defining features, determines the relative competitive advantage of visual stimuli within multiple stages of the visual system. PMID:16514108

  17. Single exposure to cocaine impairs aspartate uptake in the pre-frontal cortex via dopamine D1-receptor dependent mechanisms.

    PubMed

    Sathler, Matheus Figueiredo; Stutz, Bernardo; Martins, Robertta Silva; Dos Santos Pereira, Maurício; Pecinalli, Ney Roner; Santos, Luis E; Taveira-da-Silva, Rosilane; Lowe, Jennifer; de Freitas, Isis Grigorio; de Melo Reis, Ricardo Augusto; Manhães, Alex C; Kubrusly, Regina C C

    2016-08-01

    Dopamine and glutamate play critical roles in the reinforcing effects of cocaine. We demonstrated that a single intraperitoneal administration of cocaine induces a significant decrease in [(3)H]-d-aspartate uptake in the pre-frontal cortex (PFC). This decrease is associated with elevated dopamine levels, and requires dopamine D1-receptor signaling (D1R) and adenylyl cyclase activation. The effect was observed within 10min of cocaine administration and lasted for up to 30min. This rapid response is related to D1R-mediated cAMP-mediated activation of PKA and phosphorylation of the excitatory amino acid transporters EAAT1, EAAT2 and EAAT3. We also demonstrated that cocaine exposure increases extracellular d-aspartate, l-glutamate and d-serine in the PFC. Our data suggest that cocaine activates dopamine D1 receptor signaling and PKA pathway to regulate EAATs function and extracellular EAA level in the PFC. PMID:27208619

  18. Chronic glucocorticoids exposure enhances neurodegeneration in the frontal cortex and hippocampus via NLRP-1 inflammasome activation in male mice.

    PubMed

    Hu, Wen; Zhang, Yaodong; Wu, Wenning; Yin, Yanyan; Huang, Dake; Wang, Yuchan; Li, Weiping; Li, Weizu

    2016-02-01

    Neuroinflammation plays an important role in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD) and depression. Chronic glucocorticoids (GCs) exposure has deleterious effects on the structure and function of neurons and is associated with development and progression of AD. However, little is known about the proinflammatory effects of chronic GCs exposure on neurodegeneration in brain. Therefore, the aim of this study was to evaluate the effects of chronic dexamethasone (DEX) treatment (5mg/kg, s.c. for 7, 14, 21 and 28 days) on behavior, neurodegeneration and neuroinflammatory parameters of nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 1 (NLRP-1) inflammasome in male mice. The results showed that DEX treatment for 21 and 28 days significantly reduced the spontaneous motor activity and exploratory behavior of the mice. In addition, these mice showed significant neurodegeneration and a decrease of microtubule-associated protein 2 (MAP2) in the frontal cortex and hippocampus CA3. DEX treatment for 7, 14, 21 and 28 days significantly decreased the mRNA and protein expression of glucocorticoid receptor (GR). Moreover, DEX treatment for 21 and 28 days significantly increased the proteins expression of NLRP-1, Caspase-1, Caspase-5, apoptosis associated speck-like protein (ASC), nuclear factor-κB (NF-κB), p-NF-κB, interleukin-1β (IL-1β), IL-18 and IL-6 in the frontal cortex and hippocampus brain tissue. DEX treatment for 28 days also significantly increased the mRNA expression levels of NLRP-1, Caspase-1, ASC and IL-1β. These results suggest that chronic GCs exposure may increase brain inflammation via NLRP-1 inflammasome activation and induce neurodegeneration. PMID:26434621

  19. NIRS-based hyperscanning reveals increased interpersonal coherence in superior frontal cortex during cooperation.

    PubMed

    Cui, Xu; Bryant, Daniel M; Reiss, Allan L

    2012-02-01

    We used Near-Infrared Spectroscopy (NIRS) to simultaneously measure brain activity in two people while they played a computer-based cooperation game side by side. Inter-brain activity coherence was calculated between the two participants. We found that the coherence between signals generated by participants' right superior frontal cortices increased during cooperation, but not during competition. Increased coherence was also associated with better cooperation performance. To our knowledge, this work represents the first use of a single NIRS instrument for simultaneous measurements of brain activity in two people. This study demonstrates the use of NIRS-based hyperscanning in studies of social interaction in a naturalistic environment. PMID:21933717

  20. Activities in the frontal cortex and gait performance are modulated by preparation. An fNIRS study.

    PubMed

    Suzuki, Mitsuo; Miyai, Ichiro; Ono, Takeshi; Kubota, Kisou

    2008-01-15

    Neural activities in the primary motor cortex and supplementary motor area increase during the preparation as well as execution of voluntary movements of the hand and foot. However, there are few studies concerning preparatory activities of the brain preceding walking performance. We investigated how a verbal instruction "ready" before walking affected cortical activations and walking performances using a functional near-infrared spectroscopy. Seven healthy subjects performed two locomotor tasks on a treadmill with a verbal instruction "ready" before the treadmill was started (prepared walking; PW) and without it (simple walking; SW). Cadence was smaller and stride length was longer in PW than in SW. Increases of oxygenated hemoglobin (oxyHb) in the frontal regions especially in the prefrontal and premotor cortices were greater in PW than in SW both during the preparation and walking periods. These results suggested that preparation for walking cued by a verbal instruction enhanced frontal activations both during the preparation and execution of walking as well as walking performance. PMID:17950626

  1. Evolution of posterior parietal cortex and parietal-frontal networks for specific actions in primates.

    PubMed

    Kaas, Jon H; Stepniewska, Iwona

    2016-02-15

    Posterior parietal cortex (PPC) is an extensive region of the human brain that develops relatively late and is proportionally large compared with that of monkeys and prosimian primates. Our ongoing comparative studies have led to several conclusions about the evolution of this posterior parietal region. In early placental mammals, PPC likely was a small multisensory region much like PPC of extant rodents and tree shrews. In early primates, PPC likely resembled that of prosimian galagos, in which caudal PPC (PPCc) is visual and rostral PPC (PPCr) has eight or more multisensory domains where electrical stimulation evokes different complex motor behaviors, including reaching, hand-to-mouth, looking, protecting the face or body, and grasping. These evoked behaviors depend on connections with functionally matched domains in premotor cortex (PMC) and motor cortex (M1). Domains in each region compete with each other, and a serial arrangement of domains allows different factors to influence motor outcomes successively. Similar arrangements of domains have been retained in New and Old World monkeys, and humans appear to have at least some of these domains. The great expansion and prolonged development of PPC in humans suggest the addition of functionally distinct territories. We propose that, across primates, PMC and M1 domains are second and third levels in a number of parallel, interacting networks for mediating and selecting one type of action over others. PMID:26101180

  2. Arc Regulates Experience-Dependent Persistent Firing Patterns in Frontal Cortex

    PubMed Central

    Ren, Ming; Cao, Vania; Ye, Yizhou; Manji, Husseini K.

    2014-01-01

    The brain encodes information about past experience in specific populations of neurons that communicate with one another by firing action potentials. Studies of experience-dependent neural plasticity have largely focused on individual synaptic changes in response to neuronal input. Indicative of the neuronal output transmitted to downstream neurons, persistent firing patterns are affected by prior experience in selective neuronal populations. However, little is known about the molecular and cellular mechanisms by which experience-related persistent firing patterns are regulated in specific neuronal populations. Using frontal cortical slices prepared from transgenic mice carrying a fluorescent reporter of Arc gene expression, this study investigates how behavioral experience and the activity-regulated Arc gene affect patterns of neuronal firing. We found that motor training increases Arc expression in subsets of excitatory neurons. Those neurons exhibit persistent firing in contrast to Arc-negative neurons from the same mice or neurons from the untrained mice. Furthermore, in mice carrying genetic deletion of Arc, the frontal cortical circuitry is still in place to initiate experience-dependent gene expression, but the level of persistent firing thereafter is diminished. Finally, our results showed that the emergence of persistent activity is associated with Arc-dependent changes in the function of NMDA-type glutamate receptors, rather than changes in AMPA-type receptors or membrane excitability. Our findings therefore reveal an Arc-dependent molecular pathway by which gene–experience interaction regulates the emergence of persistent firing patterns in specific neuronal populations. PMID:24806683

  3. A hierarchy of timescales explains distinct effects of local inhibition of primary visual cortex and frontal eye fields

    PubMed Central

    Cocchi, Luca; Sale, Martin V; L Gollo, Leonardo; Bell, Peter T; Nguyen, Vinh T; Zalesky, Andrew; Breakspear, Michael; Mattingley, Jason B

    2016-01-01

    Within the primate visual system, areas at lower levels of the cortical hierarchy process basic visual features, whereas those at higher levels, such as the frontal eye fields (FEF), are thought to modulate sensory processes via feedback connections. Despite these functional exchanges during perception, there is little shared activity between early and late visual regions at rest. How interactions emerge between regions encompassing distinct levels of the visual hierarchy remains unknown. Here we combined neuroimaging, non-invasive cortical stimulation and computational modelling to characterize changes in functional interactions across widespread neural networks before and after local inhibition of primary visual cortex or FEF. We found that stimulation of early visual cortex selectively increased feedforward interactions with FEF and extrastriate visual areas, whereas identical stimulation of the FEF decreased feedback interactions with early visual areas. Computational modelling suggests that these opposing effects reflect a fast-slow timescale hierarchy from sensory to association areas. DOI: http://dx.doi.org/10.7554/eLife.15252.001 PMID:27596931

  4. Effective Connectivity Hierarchically Links Temporoparietal and Frontal Areas of the Auditory Dorsal Stream with the Motor Cortex Lip Area during Speech Perception

    ERIC Educational Resources Information Center

    Murakami, Takenobu; Restle, Julia; Ziemann, Ulf

    2012-01-01

    A left-hemispheric cortico-cortical network involving areas of the temporoparietal junction (Tpj) and the posterior inferior frontal gyrus (pIFG) is thought to support sensorimotor integration of speech perception into articulatory motor activation, but how this network links with the lip area of the primary motor cortex (M1) during speech…

  5. AGE-RELATED CHANGES IN NEUTRAL SPHINGOMYELIN-SPECIFIC PHOSPHOLIPASE C ACTIVITY IN STRIATUM, HIPPOCAMPUS, AND FRONTAL CORTEX: IMPLICATION FOR SENSITIVITY TO STRESS AND INFLAMMATION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous studies show the enrichment of mammalian brain with neutral sphingomyelin specific phospholipase C (ceramide-phosphocholine phosphodiesterase, EC 3.1.4.12; N-Sase). The objective of this study was to evaluate the subcellular N-Sase activity in striatum, hippocampus, and frontal cortex. Resu...

  6. Investigation of human frontal cortex under noxious thermal stimulation of temporo-mandibular joint using functional near infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Yennu, Amarnath; Rawat, Rohit; Manry, Michael T.; Gatchel, Robert; Liu, Hanli

    2013-03-01

    According to American Academy of Orofacial Pain, 75% of the U.S. population experiences painful symptoms of temporo-mandibular joint and muscle disorder (TMJMD) during their lifetime. Thus, objective assessment of pain is crucial for efficient pain management. We used near infrared spectroscopy (NIRS) as a tool to explore hemodynamic responses in the frontal cortex to noxious thermal stimulation of temporomadibular joint (TMJ). NIRS experiments were performed on 9 healthy volunteers under both low pain stimulation (LPS) and high pain stimulation (HPS), using a temperature-controlled thermal stimulator. To induce thermal pain, a 16X16 mm2 thermode was strapped onto the right TMJ of each subject. Initially, subjects were asked to rate perceived pain on a scale of 0 to 10 for the temperatures from 41°C to 47°C. For the NIRS measurement, two magnitudes of temperatures, one rated as 3 and another rated as 7, were chosen as LPS and HPS, respectively. By analyzing the temporal profiles of changes in oxy-hemoglobin concentration (HbO) using cluster-based statistical tests, we were able to identify several regions of interest (ROI), (e.g., secondary somatosensory cortex and prefrontal cortex), where significant differences (p<0.05) between HbO responses to LPS and HPS are shown. In order to classify these two levels of pain, a neural-network-based classification algorithm was used. With leave-one-out cross validation from 9 subjects, the two levels of pain were identified with 100% mean sensitivity, 98% mean specificity and 99% mean accuracy to high pain. From the receiver operating characteristics curve, 0.99 mean area under curve was observed.

  7. Electrical stimulation of the frontal cortex enhances slow-frequency EEG activity and sleepiness.

    PubMed

    D'Atri, A; De Simoni, E; Gorgoni, M; Ferrara, M; Ferlazzo, F; Rossini, P M; De Gennaro, L

    2016-06-01

    Our aim was to enhance the spontaneous slow-frequency EEG activity during the resting state using oscillating transcranial direct currents (tDCS) with a stimulation frequency that resembles the spontaneous oscillations of sleep onset. Accordingly, in this preliminary study, we assessed EEG after-effects of a frontal oscillatory tDCS with different frequency (0.8 vs. 5Hz) and polarity (anodal, cathodal, and sham). Two single-blind experiments compared the after effects on the resting EEG of oscillatory tDCS [Exp. 1=0.8Hz, 10 subjects (26.2±2.5years); Exp. 2=5Hz, 10 subjects (27.4±2.4years)] by manipulating its polarity. EEG signals recorded (28 scalp derivations) before and after stimulation [slow oscillations (0.5-1Hz), delta (1-4Hz), theta (5-7Hz), alpha (8-12Hz), beta 1 (13-15Hz) and beta 2 (16-24Hz)] were compared between conditions as a function of polarity (anodal vs. cathodal vs. sham) and frequency of stimulation (0.8 vs. 5Hz). We found a significant relative enhancement of the delta activity after the anodal tDCS at 5Hz compared to that at 0.8Hz. This increase, even though not reaching the statistical significance compared to sham, is concomitant to a significant increase of subjective sleepiness, as assessed by a visual analog scale. These two phenomena are linearly related with a regional specificity, correlations being restricted to cortical areas perifocal to the stimulation site. We have shown that a frontal oscillating anodal tDCS at 5Hz results in an effective change of both subjective sleepiness and spontaneous slow-frequency EEG activity. These changes are critically associated to both stimulation polarity (anodal) and frequency (5Hz). However, evidence of frequency-dependence seems more unequivocal than evidence of polarity-dependence. PMID:26964682

  8. Short theta burst stimulation to left frontal cortex prior to encoding enhances subsequent recognition memory.

    PubMed

    Demeter, Elise; Mirdamadi, Jasmine L; Meehan, Sean K; Taylor, Stephan F

    2016-08-01

    Deep semantic encoding of verbal stimuli can aid in later successful retrieval of those stimuli from long-term episodic memory. Evidence from numerous neuropsychological and neuroimaging experiments demonstrate regions in left prefrontal cortex, including left dorsolateral prefrontal cortex (DLPFC), are important for processes related to encoding. Here, we investigated the relationship between left DLPFC activity during encoding and successful subsequent memory with transcranial magnetic stimulation (TMS). In a pair of experiments using a 2-session within-subjects design, we stimulated either left DLPFC or a control region (Vertex) with a single 2-s train of short theta burst stimulation (sTBS) during a semantic encoding task and then gave participants a recognition memory test. We found that subsequent memory was enhanced on the day left DLPFC was stimulated, relative to the day Vertex was stimulated, and that DLPFC stimulation also increased participants' confidence in their decisions during the recognition task. We also explored the time course of how long the effects of sTBS persisted. Our data suggest 2 s of sTBS to left DLPFC is capable of enhancing subsequent memory for items encoded up to 15 s following stimulation. Collectively, these data demonstrate sTBS is capable of enhancing long-term memory and provide evidence that TBS protocols are a potentially powerful tool for modulating cognitive function. PMID:27098772

  9. The origins of thalamic inputs to grasp zones in frontal cortex of macaque monkeys.

    PubMed

    Gharbawie, Omar A; Stepniewska, Iwona; Kaas, Jon H

    2016-07-01

    The hand representation in primary motor cortex (M1) is instrumental to manual dexterity in primates. In Old World monkeys, rostral and caudal aspects of the hand representation are located in the precentral gyrus and the anterior bank of the central sulcus, respectively. We previously reported the organization of the cortico-cortical connections of the grasp zone in rostral M1. Here we describe the organization of thalamocortical connections that were labeled from the same tracer injections. Thalamocortical connections of a grasp zone in ventral premotor cortex (PMv) and the M1 orofacial representation are included for direct comparison. The M1 grasp zone was primarily connected with ventral lateral divisions of motor thalamus. The largest proportion of inputs originated in the posterior division (VLp) followed by the medial and the anterior divisions. Thalamic inputs to the M1 grasp zone originated in more lateral aspects of VLp as compared to the origins of thalamic inputs to the M1 orofacial representation. Inputs to M1 from thalamic divisions connected with cerebellum constituted three fold the density of inputs from divisions connected with basal ganglia, whereas the ratio of inputs was more balanced for the grasp zone in PMv. Privileged access of the cerebellothalamic pathway to the grasp zone in rostral M1 is consistent with the connection patterns previously reported for the precentral gyrus. Thus, cerebellar nuclei are likely more involved than basal ganglia nuclei with the contributions of rostral M1 to manual dexterity. PMID:26254903

  10. Sustaining high acetylcholine levels in the frontal cortex, but not retrosplenial cortex, recovers spatial memory performance in a rodent model of diencephalic amnesia.

    PubMed

    Savage, Lisa M

    2012-04-01

    Although the thalamus and/or mammillary bodies are the primary sites of neuropathology in cases of diencephalic amnesia such as Wernicke Korsakoff Syndrome (WKS), there is also functional deactivation of certain cortical regions that contribute to the cognitive dysfunction. Acetylcholine (ACh) is a key neurotransmitter that modulates neural processing within the cortex and between the thalamus and cortex. In the pyrithiamine-induced thiamine deficiency (PTD) rat model of WKS, there are significant reductions in cholinergic innervation and behaviorally stimulated ACh efflux in the frontal (FC) and retrosplenial (RSC) cortices. In the present study, ACh released levels were site-specifically amplified with physostigmine (0.5 μg, 1.0 μg) in the FC and the RSC, which was confirmed with in vivo microdialysis. Although physostigmine sustained high ACh levels in both cortical regions, the effects on spatial memory, assessed by spontaneous alternation, were different as a function of region (FC, RSC) and treatment (PTD, pair-fed [PF]). Higher ACh levels in the FC recovered the rate of alternation in PTD rats as well as reduced arm-reentry perseverative errors. However, higher ACh levels within the FC of PF rats exacerbated arm-reentry perseverative errors without significantly affecting alternation rates. Maintaining high ACh levels in the RSC had no procognitive effects in PTD rats, but rather impaired alternation behavior in PF rats. These results demonstrate that diverse cortical regions respond differently to intensified ACh levels-and the effects are dependent on thalamic pathology. Thus, pharmacotherapeutics aimed at enhancing cognitive functions must account for the unique features of cortical ACh stimulation and the connective circuitry with the thalamus. PMID:22448856

  11. Sustaining high acetylcholine levels in the frontal cortex, but not retrosplenial cortex, recovers spatial memory performance in a rodent model of diencephalic amnesia

    PubMed Central

    Savage, Lisa M.

    2012-01-01

    Although the thalamus and/or mammillary bodies are the primary sites of neuropathology in cases of diencephalic amnesia such as Wernicke Korsakoff Syndrome (WKS), there is also functional deactivation of certain cortical regions that contribute to the cognitive dysfunction. Acetylcholine (ACh) is a key neurotransmitter that modulates neural processing within the cortex and between the thalamus and cortex. In the pyrithiamine-induced thiamine deficiency (PTD) rat model of WKS there are significant reductions in cholinergic innervation and behaviorally-stimulated ACh efflux in the frontal (FC) and retrosplenial (RSC) cortices. In the present study, ACh released levels were site-specifically amplified with physostigmine (0.5 μg, 1.0 μg) in the FC and the RSC, which was confirmed with in vivo microdialysis. Although physostigmine sustained high ACh levels in both cortical regions, the effects on spatial memory, assessed by spontaneous alternation, were different as a function of region (FC, RSC) and treatment (PTD, pair-fed [PF]). Higher ACh levels in the FC recovered the rate of alternation in PTD rats as well as reduced arm-re-entry preservative errors. However, higher ACh levels within the FC of PF rats exacerbated arm-re-entry preservative errors without significantly affecting alternation rates. Maintaining high ACh levels in the RSC had no procognitive effects in PTD rats, but rather impaired alternation behavior in PF rats. These results demonstrate that diverse cortical regions respond differently to intensified ACh levels—and the effects are dependent on thalamic pathology. Thus, pharmacotherapeutics aimed at enhancing cognitive functions must account for the unique features of cortical ACh stimulation and the connective circuitry with the thalamus. PMID:22448856

  12. Inferior frontal cortex activity is modulated by reward sensitivity and performance variability.

    PubMed

    Fuentes-Claramonte, Paola; Ávila, César; Rodríguez-Pujadas, Aina; Costumero, Víctor; Ventura-Campos, Noelia; Bustamante, Juan Carlos; Rosell-Negre, Patricia; Barrós-Loscertales, Alfonso

    2016-02-01

    High reward sensitivity has been linked with motivational and cognitive disorders related with prefrontal and striatal brain function during inhibitory control. However, few studies have analyzed the interaction among reward sensitivity, task performance and neural activity. Participants (N=57) underwent fMRI while performing a Go/No-go task with Frequent-go (77.5%), Infrequent-go (11.25%) and No-go (11.25%) stimuli. Task-associated activity was found in inhibition-related brain regions, with different activity patterns for right and left inferior frontal gyri (IFG): right IFG responded more strongly to No-go stimuli, while left IFG responded similarly to all infrequent stimuli. Reward sensitivity correlated with omission errors in Go trials and reaction time (RT) variability, and with increased activity in right and left IFG for No-go and Infrequent-go stimuli compared with Frequent-go. Bilateral IFG activity was associated with RT variability, with reward sensitivity mediating this association. These results suggest that reward sensitivity modulates behavior and brain function during executive control. PMID:26772873

  13. Alcohol abuse and HIV infection have additive effects on frontal cortex function as measured by auditory evoked potential P3A latency.

    PubMed

    Fein, G; Biggins, C A; MacKay, S

    1995-02-01

    Both alcohol and human immunodeficiency virus (HIV) infection have been shown to produce central nervous system (CNS) morbidity in frontal brain regions. The degree to which the CNS morbidity in HIV infection, as it affects frontal cortex function, may be preferentially increased by alcohol abuse was examined using the auditory P3A evoked potential. The P3A indexes an orienting response, maximal over frontal cortex that occurs when novel nontarget stimuli are presented in the midst of a target detection paradigm. Four groups of subjects were compared: HIV+ alcohol abusers, HIV+ light/nondrinkers, HIV- alcohol abusers, and HIV- light/nondrinkers. The alcohol abuser and light/nondrinker HIV+ groups were matched on percent CD4 lymphocytes, insuring that the results reflected specific CNS effects and were not a result of differences between the groups in the degree of systemic immune suppression. Alcohol abuse and HIV infection had at least additive effects on P3A latency, consistent with alcohol abuse worsening the effect of HIV disease on frontal cortex function. Post-hoc analyses suggested that concomitant alcohol abuse results in the effects of HIV infection on P3A latency becoming manifest earlier in the HIV disease process. PMID:7727627

  14. The development of performance-monitoring function in the posterior medial frontal cortex

    PubMed Central

    Fitzgerald, Kate Dimond; Perkins, Suzanne C.; Angstadt, Mike; Johnson, Timothy; Stern, Emily R.; Welsh, Robert C.; Taylor, Stephan F.

    2009-01-01

    Background Despite its critical role in performance-monitoring, the development of posterior medial prefrontal cortex (pMFC) in goal-directed behaviors remains poorly understood. Performance monitoring depends on distinct, but related functions that may differentially activate the pMFC, such as monitoring response conflict and detecting errors. Developmental differences in conflict- and error-related activations, coupled with age-related changes in behavioral performance, may confound attempts to map the maturation of pMFC functions. To characterize the development of pMFC-based performance monitoring functions, we segregated interference and error-processing, while statistically controlling for performance. Methods Twenty-one adults and 23 youth performed an event-related version of the Multi-Source Interference Task during functional magnetic resonance imaging (fMRI). Linear modeling of interference and error contrast estimates derived from the pMFC were regressed on age, while covarying for performance. Results Interference- and error-processing were associated with robust activation of the pMFC in both youth and adults. Among youth, interference- and error-related activation of the pMFC increased with age, independent of performance. Greater accuracy associated with greater pMFC activity during error commission in both groups. Discussion Increasing pMFC response to interference and errors occurs with age, likely contributing to the improvement of performance monitoring capacity during development. PMID:19913101

  15. Increase of glucose consumption in basal ganglia, thalamus and frontal cortex of patients with spasmodic torticollis

    SciTech Connect

    Grassi, F.; Bressi, S.; Antoni, M.

    1994-05-01

    The pathophysiology of spasmodic torticollis, a focal dystonia involving neck muscles, is still unclear. Positron emission tomography (PET) studies showed either an increase as well as a decrease of regional cerebral metabolic rate of glucose (rCMRglu) in basal ganglia. In the present study, [18F]FDG and PET was used to measure rCMRglu in 10 patients with spasmodic torticollis (mean age 50.37 {plus_minus} 11.47) and 10 age matched controls. All cases with a short disease duration, were untreated. A factorial analysis of variance revealed a significant bilateral increase of glucose consumption in caudate nucleus and pallidum/putamen complex (p>0.004) and in the cerebellum (p>0.001). The rCMRglu increase in the motor/premotor cortex and in the thalamus reached a trend towards significance (p<0.05). These preliminary data show enhanced metabolism in basal ganglia and cerebellum as the functional correlate of focal dystonia. A recently proposed model suggests that dystonia would be the consequence of a putaminal hyperactivity, leading to the breakdown of the pallidal inhibitory control on thalamus and thalamo-cortical projections.

  16. Laser-induced accurate frontal cortex damage: a new tool for brain study

    NASA Astrophysics Data System (ADS)

    Flores, Gonzalo; Khotiaintsev, Sergei N.; Sanchez-Huerta, Maria L.; Ibanes, Osvaldo; Hernandez, Adan; Silva, Adriana B.; Calderon, Rafael; Ayala, Griselda; Marroquin, Javier; Svirid, Vladimir; Khotiaintsev, Yuri V.

    1999-01-01

    New laser-based technique for anatomical-functional study of the medial prefrontal cortex (MPFC) of the brain of experimental animals (rats) is presented. The technique is based on making accurate well-controlled lesions to small MPFC and subsequent observing behavioral alterations in the lesioned animals relative to control ones. Laser produces smaller and more accurate lesions in comparison to those obtained by traditional methods, such as: mechanical action, chemical means, and electrical currents. For producing the brain lesions, a 10 W CO2 CW laser is employed for reasons of its sufficiently high power, which is combined with relatively low cost-per-Watt ratio. In our experience, such power rating is sufficient for making MPFC lesions. The laser radiation is applied in a form of pulse series via hollow circular metallic waveguide made of stainless steel. The waveguide is of inner diameter 1.3 mm and 95 mm long. The anesthetized animals are placed in stereotaxic instrument. Via perforations made in the skull bone, the MPFC is exposed to the laser radiation. Several weeks later (after animal recuperation), standard behavioral tests are performed. They reveal behavioral changes, which point to a damage of some small regions of the MPFC. These results correlate with the histological data, which reveal the existence of small and accurate MPFC lesions. The present technique has good prospects for use in anatomical- functional studies of brain by areas. In addition, this technique appears to have considerable promise as a treatment method for some pathologies, e.g. the Parkinson's disease.

  17. In search of the functional neuroanatomy of sociality: MRI subdivisions of orbital frontal cortex and social cognition

    PubMed Central

    Nakamura, Motoaki; Niznikiewicz, Margaret; Thompson, Elizabeth; Levitt, James J.; Choate, Victoria; Shenton, Martha E.; McCarley, Robert W.

    2013-01-01

    We examined social cognition in a sample of healthy participants who had prior magnetic resonance imaging (MRI) gray matter volume studies of the orbital frontal cortex (OFC) that was parcellated into three regions: gyrus rectus, middle orbital gyrus and lateral orbital gyrus. These subjects also completed a self-report measure of Machiavelli personality traits, along with psychometric tests of social comprehension and declarative episodic memory, all of which we used as proxy measures to examine various features of social cognition. The data pointed to distinct functional–anatomical relationships highlighted by strong correlations of left lateral orbital gyrus and Machiavellian scores and right middle orbital gyrus with social comprehension and declarative episodic memory. In addition, hierarchical regression analyses revealed statistical evidence of a double dissociation between Machiavellian scores and left lateral orbital gyrus on one hand, and social comprehension with right middle orbital gyrus, on the other hand. To our knowledge, these findings are the first to show evidence linking normal variation in OFC subregions and different aspects of social cognition. PMID:22345366

  18. Mitochondrial dysfunction and lipid peroxidation in rat frontal cortex by chronic NMDA administration can be partially prevented by lithium treatment.

    PubMed

    Kim, Helena K; Isaacs-Trepanier, Cameron; Elmi, Nika; Rapoport, Stanley I; Andreazza, Ana C

    2016-05-01

    Chronic N-methyl-d-aspartate (NMDA) administration to rats may be a model to investigate excitotoxicity mediated by glutamatergic hyperactivity, and lithium has been reported to be neuroprotective. We hypothesized that glutamatergic hyperactivity in chronic NMDA injected rats would cause mitochondrial dysfunction and lipid peroxidation in the brain, and that chronic lithium treatment would ameliorate some of these NMDA-induced alterations. Rats treated with lithium for 6 weeks were injected i.p. 25 mg/kg NMDA on a daily basis for the last 21 days of lithium treatment. Brain was removed and frontal cortex was analyzed. Chronic NMDA decreased brain levels of mitochondrial complex I and III, and increased levels of the lipid oxidation products, 8-isoprostane and 4-hydroxynonenal, compared with non-NMDA injected rats. Lithium treatment prevented the NMDA-induced increments in 8-isoprostane and 4-hydroxynonenal. Our findings suggest that increased chronic activation of NMDA receptors can induce alterations in electron transport chain complexes I and III and in lipid peroxidation in brain. The NMDA-induced changes may contribute to glutamate-mediated excitotoxicity, which plays a role in brain diseases such as bipolar disorder. Lithium treatment prevented changes in 8-isoprostane and 4-hydroxynonenal, which may contribute to lithium's reported neuroprotective effect and efficacy in bipolar disorder. PMID:26894301

  19. Do Defense Styles of Ego Relate to Volumes of Orbito-Frontal Cortex in Patients with Obsessive-Compulsive Disorder?

    PubMed Central

    Yildirim, Hanefi; Koc, Mustafa; Korkmaz, Sevda; Ozler, Sinan; Erenkus, Zehra

    2011-01-01

    Objective Although the importance of orbito-frontal cortex (OFC) is established in the pathogenesis of obsessive compulsive disorder (OCD), no study have evaluated its relation to the traditional psychodynamic perspective. In the present study, we aimed to evaluate the relationship between the defense styles consisting of mature, immature and neurotic defenses and OFC volumes of patients with OCD. Methods Subjects were selected among those of our previous study, and so eighteen patients with OCD and same number of healthy controls were took into the study. The patients and controls had underwent magnetic resonance imaging (MRI). In addition, the Defense Style Questionnaire-40 was administered to obtain defense styles of patients and controls. Results No significant relationship was found between the right OFC volumes of both the patient and control groups and their scores of mature, neurotic, or immature defense mechanisms. As for the left OFC volumes, the only significant relationship for the scores of immature defense mechanism was found in the patient group. Conclusion The results of the present study indicated that there was no significant relationship between OFC volumes of the patient group and their scores of mature, neurotic, or immature defense mechanisms, except a significant relation with the scores of immature defense mechanisms. PMID:21852988

  20. Early Alzheimer's disease-type pathology in the frontal cortex of wild mountain gorillas (Gorilla beringei beringei).

    PubMed

    Perez, Sylvia E; Sherwood, Chet C; Cranfield, Michael R; Erwin, Joseph M; Mudakikwa, Antoine; Hof, Patrick R; Mufson, Elliott J

    2016-03-01

    Amyloid beta (Aβ) and tau pathology have been described in the brains of captive aged great apes, but the natural progression of these age-related pathologies from wild great apes, including the gorilla, is unknown. In our previous study of Western lowland gorillas (Gorilla gorilla gorilla) who were housed in American Zoos and Aquariums-accredited facilities, we found an age-related increase in Aβ-positive plaques and vasculature, tau-positive astrocytes, oligodendrocyte coiled bodies, and neuritic clusters in the neocortex as well as hippocampus in older animals. Here, we demonstrate that aged wild mountain gorillas (Gorilla beringei beringei), who spent their entire lives in their natural habitat, also display an age-related increase in amyloid precursor protein (APP) and/or Aβ-immunoreactive blood vessels and plaques, but very limited tau pathology, in the frontal cortex. These results indicate that Aβ and tau lesions are age-related events that occur in the brain of gorillas living in captivity and in the wild. PMID:26923416

  1. Allopregnanolone and progesterone decrease cell death and cognitive deficits after a contusion of the rat pre-frontal cortex.

    PubMed

    Djebaili, M; Hoffman, S W; Stein, D G

    2004-01-01

    We compared the effects of three different doses of allopregnanolone (4, 8 or 16 mg/kg), a metabolite of progesterone, to progesterone (16 mg/kg) in adult rats with controlled cortical impact to the pre-frontal cortex. Injections were given 1 h, 6 h and every day for 5 consecutive days after the injury. One day after injury, both progesterone-treated (16 mg/kg) and allopregnanolone (8 or 16 mg/kg)-treated rats showed less caspase-3 activity, and rats treated with allopregnanolone (16 mg/kg) showed less DNA fragmentation in the lesion area, indicating reduced apoptosis. Nineteen days after the injury, rats treated with progesterone and allopregnanolone (8 or 16 mg/kg) showed no difference in necrotic cavity size but had less cell loss in the medio-dorsal nucleus of the thalamus and less learning and memory impairments compared with the injured vehicle-treated rats. On that same day the injured rats treated with progesterone showed more weight gain compared with the injured rats treated with the vehicle. These results can be taken to show that progesterone and allopregnanolone have similar neuroprotective effects after traumatic brain injury, but allopregnanolone appears to be more potent than progesterone in facilitating CNS repair. PMID:14698743

  2. How Two Brains Make One Synchronized Mind in the Inferior Frontal Cortex: fNIRS-Based Hyperscanning During Cooperative Singing

    PubMed Central

    Osaka, Naoyuki; Minamoto, Takehiro; Yaoi, Ken; Azuma, Miyuki; Shimada, Yohko Minamoto; Osaka, Mariko

    2015-01-01

    One form of communication that is common in all cultures is people singing together. Singing together reflects an index of cognitive synchronization and cooperation of human brains. Little is known about the neural synchronization mechanism, however. Here, we examined how two brains make one synchronized behavior using cooperated singing/humming between two people and hyperscanning, a new brain scanning technique. Hyperscanning allowed us to observe dynamic cooperation between interacting participants. We used functional near-infrared spectroscopy (fNIRS) to simultaneously record the brain activity of two people while they cooperatively sang or hummed a song in face-to-face (FtF) or face-to-wall (FtW) conditions. By calculating the inter-brain wavelet transform coherence between two interacting brains, we found a significant increase in the neural synchronization of the left inferior frontal cortex (IFC) for cooperative singing or humming regardless of FtF or FtW compared with singing or humming alone. On the other hand, the right IFC showed an increase in neural synchronization for humming only, possibly due to more dependence on musical processing. PMID:26635703

  3. Differential Gene Expression in the Nucleus Accumbens and Frontal Cortex of Lewis and Fischer 344 Rats Relevant to Drug Addiction

    PubMed Central

    Higuera-Matas, A; Montoya, G. L; Coria, S.M; Miguéns, M; García-Lecumberri, C; Ambrosio, E

    2011-01-01

    Drug addiction results from the interplay between social and biological factors. Among these, genetic variables play a major role. The use of genetically related inbred rat strains that differ in their preference for drugs of abuse is one approach of great importance to explore genetic determinants. Lewis and Fischer 344 rats have been extensively studied and it has been shown that the Lewis strain is especially vulnerable to the addictive properties of several drugs when compared with the Fischer 344 strain. Here, we have used microarrays to analyze gene expression profiles in the frontal cortex and nucleus accumbens of Lewis and Fischer 344 rats. Our results show that only a very limited group of genes were differentially expressed in Lewis rats when compared with the Fischer 344 strain. The genes that were induced in the Lewis strain were related to oxygen transport, neurotransmitter processing and fatty acid metabolism. On the contrary genes that were repressed in Lewis rats were involved in physiological functions such as drug and proton transport, oligodendrocyte survival and lipid catabolism. These data might be useful for the identification of genes which could be potential markers of the vulnerability to the addictive properties of drugs of abuse. PMID:21886580

  4. How Two Brains Make One Synchronized Mind in the Inferior Frontal Cortex: fNIRS-Based Hyperscanning During Cooperative Singing.

    PubMed

    Osaka, Naoyuki; Minamoto, Takehiro; Yaoi, Ken; Azuma, Miyuki; Shimada, Yohko Minamoto; Osaka, Mariko

    2015-01-01

    One form of communication that is common in all cultures is people singing together. Singing together reflects an index of cognitive synchronization and cooperation of human brains. Little is known about the neural synchronization mechanism, however. Here, we examined how two brains make one synchronized behavior using cooperated singing/humming between two people and hyperscanning, a new brain scanning technique. Hyperscanning allowed us to observe dynamic cooperation between interacting participants. We used functional near-infrared spectroscopy (fNIRS) to simultaneously record the brain activity of two people while they cooperatively sang or hummed a song in face-to-face (FtF) or face-to-wall (FtW) conditions. By calculating the inter-brain wavelet transform coherence between two interacting brains, we found a significant increase in the neural synchronization of the left inferior frontal cortex (IFC) for cooperative singing or humming regardless of FtF or FtW compared with singing or humming alone. On the other hand, the right IFC showed an increase in neural synchronization for humming only, possibly due to more dependence on musical processing. PMID:26635703

  5. Greater Activity in the Frontal Cortex on Left Curves: A Vector-Based fNIRS Study of Left and Right Curve Driving

    PubMed Central

    Oka, Noriyuki; Yoshino, Kayoko; Yamamoto, Kouji; Takahashi, Hideki; Li, Shuguang; Sugimachi, Toshiyuki; Nakano, Kimihiko; Suda, Yoshihiro; Kato, Toshinori

    2015-01-01

    Objectives In the brain, the mechanisms of attention to the left and the right are known to be different. It is possible that brain activity when driving also differs with different horizontal road alignments (left or right curves), but little is known about this. We found driver brain activity to be different when driving on left and right curves, in an experiment using a large-scale driving simulator and functional near-infrared spectroscopy (fNIRS). Research Design and Methods The participants were fifteen healthy adults. We created a course simulating an expressway, comprising straight line driving and gentle left and right curves, and monitored the participants under driving conditions, in which they drove at a constant speed of 100 km/h, and under non-driving conditions, in which they simply watched the screen (visual task). Changes in hemoglobin concentrations were monitored at 48 channels including the prefrontal cortex, the premotor cortex, the primary motor cortex and the parietal cortex. From orthogonal vectors of changes in deoxyhemoglobin and changes in oxyhemoglobin, we calculated changes in cerebral oxygen exchange, reflecting neural activity, and statistically compared the resulting values from the right and left curve sections. Results Under driving conditions, there were no sites where cerebral oxygen exchange increased significantly more during right curves than during left curves (p > 0.05), but cerebral oxygen exchange increased significantly more during left curves (p < 0.05) in the right premotor cortex, the right frontal eye field and the bilateral prefrontal cortex. Under non-driving conditions, increases were significantly greater during left curves (p < 0.05) only in the right frontal eye field. Conclusions Left curve driving was thus found to require more brain activity at multiple sites, suggesting that left curve driving may require more visual attention than right curve driving. The right frontal eye field was activated under both

  6. Agranular platelets as a cardinal feature of ARC syndrome.

    PubMed

    Kim, Seong Min; Chang, Hye Kyung; Song, Jae Woo; Koh, Hong; Han, Seok Joo

    2010-05-01

    We aimed to describe abnormal platelet morphology and its clinical significance in infants who were diagnosed with arthrogryposis renal dysfunction and cholestasis (ARC) syndrome. We collected all of the cases of ARC syndrome referred to a single pediatric referral center. In all patients, platelet counts and analysis of platelet morphology were performed with peripheral blood smear specimens. Electron microscopy images were obtained to examine the ultrastructure of the platelets. Over the 12-year period, 12 cases of ARC syndrome were identified. The sex ratio (male:female) was 1:1. The median birth weight was 3.15 kg (range, 2.3 to 3.8 kg). Failure to thrive was observed in all the patients. The major cause of death was recurrent febrile illness and pneumonia. The median age at death was 8.9 months (range, 2.6 to 28.8 kg). Their median body weight at death was 3.1 kg (range, 2.6 to 6.0 kg). Close examination of their peripheral blood smear (n=11) specimens showed large, pale, agranular platelets similar to those seen in gray platelet syndrome. Electron microscopic images of the platelets (n=7) revealed a lack of alpha; granules. Agranular platelets are a common finding in ARC syndrome. Agranular platelets should be considered as a cardinal feature of ARC syndrome and can be useful as a noninvasive diagnostic marker for ARC syndrome. PMID:20224444

  7. Propofol-Induced Frontal Cortex Disconnection: A Study of Resting-State Networks, Total Brain Connectivity, and Mean BOLD Signal Oscillation Frequencies.

    PubMed

    Guldenmund, Pieter; Gantner, Ithabi S; Baquero, Katherine; Das, Tushar; Demertzi, Athena; Boveroux, Pierre; Bonhomme, Vincent; Vanhaudenhuyse, Audrey; Bruno, Marie-Aurélie; Gosseries, Olivia; Noirhomme, Quentin; Kirsch, Muriëlle; Boly, Mélanie; Owen, Adrian M; Laureys, Steven; Gómez, Francisco; Soddu, Andrea

    2016-04-01

    Propofol is one of the most commonly used anesthetics in the world, but much remains unknown about the mechanisms by which it induces loss of consciousness. In this resting-state functional magnetic resonance imaging study, we examined qualitative and quantitative changes of resting-state networks (RSNs), total brain connectivity, and mean oscillation frequencies of the regional blood oxygenation level-dependent (BOLD) signal, associated with propofol-induced mild sedation and loss of responsiveness in healthy subjects. We found that detectability of RSNs diminished significantly with loss of responsiveness, and total brain connectivity decreased strongly in the frontal cortex, which was associated with increased mean oscillation frequencies of the BOLD signal. Our results suggest a pivotal role of the frontal cortex in propofol-induced loss of responsiveness. PMID:26650183

  8. Repeated treatment with electroconvulsive seizures induces HDAC2 expression and down-regulation of NMDA receptor-related genes through histone deacetylation in the rat frontal cortex.

    PubMed

    Park, Hong Geun; Yu, Hyun Sook; Park, Soyoung; Ahn, Yong Min; Kim, Yong Sik; Kim, Se Hyun

    2014-09-01

    The enzymatic activity of histone deacetylases (HDACs) leads to a histone deacetylation-mediated condensed chromatic structure, resulting in transcriptional repression, which has been implicated in the modifications of neural circuits and behaviors. Repeated treatment with electroconvulsive seizure (ECS) induces changes in histone acetylation, expression of various genes, and intrabrain cellular changes, including neurogenesis. In this study, we examined the effects of repeated ECS on the expression of class I HDACs and related changes in histone modifications and gene expression in the rat frontal cortex. Ten days of repeated ECS treatments (E10X) up-regulated HDAC2 expression at the mRNA and protein levels in the rat frontal cortex compared with sham-treated controls; this was evident in the nuclei of neuronal cells in the prefrontal, cingulate, orbital, and insular cortices. Among the known HDAC2 target genes, mRNA expression of N-methyl-d-aspartate (NMDA) receptor signaling-related genes, including early growth response-1 (Egr1), c-Fos, glutamate receptor, ionotropic, N-methyl d-aspartate 2A (Nr2a), Nr2b, neuritin1 (Nrn1), and calcium/calmodulin-dependent protein kinase II alpha (Camk2α), were decreased, and the histone acetylation of H3 and/or H4 proteins was also reduced by E10X. Chromatin immunoprecipitation analysis revealed that HDAC2 occupancy in the promoters of down-regulated genes was increased significantly. Moreover, administration of sodium butyrate, a HDAC inhibitor, during the course of E10X ameliorated the ECS-induced down-regulation of genes in the rat frontal cortex. These findings suggest that induction of HDAC2 by repeated ECS treatment could play an important role in the down-regulation of NMDA receptor signaling-related genes in the rat frontal cortex through histone modification. PMID:24606669

  9. The enhanced information flow from visual cortex to frontal area facilitates SSVEP response: evidence from model-driven and data-driven causality analysis

    PubMed Central

    Li, Fali; Tian, Yin; Zhang, Yangsong; Qiu, Kan; Tian, Chunyang; Jing, Wei; Liu, Tiejun; Xia, Yang; Guo, Daqing; Yao, Dezhong; Xu, Peng

    2015-01-01

    The neural mechanism of steady-state visual evoked potentials (SSVEP) is still not clearly understood. Especially, only certain frequency stimuli can evoke SSVEP. Our previous network study reveals that 8 Hz stimulus that can evoke strong SSVEP response shows the enhanced linkage strength between frontal and visual cortex. To further probe the directed information flow between the two cortex areas for various frequency stimuli, this paper develops a causality analysis based on the inversion of double columns model using particle swarm optimization (PSO) to characterize the directed information flow between visual and frontal cortices with the intracranial rat electroencephalograph (EEG). The estimated model parameters demonstrate that the 8 Hz stimulus shows the enhanced directional information flow from visual cortex to frontal lobe facilitates SSVEP response, which may account for the strong SSVEP response for 8 Hz stimulus. Furthermore, the similar finding is replicated by data-driven causality analysis. The inversion of neural mass model proposed in this study may be helpful to provide the new causality analysis to link the physiological model and the observed datasets in neuroscience and clinical researches. PMID:26434769

  10. Changes in regional cerebral blood volume in frontal cortex during mental work with and without caffeine intake: functional monitoring using near-infrared spectroscopy.

    PubMed

    Higashi, Terumasa; Sone, Yukari; Ogawa, Kanta; Kitamura, Yuri T; Saiki, Kayoko; Sagawa, Setsuko; Yanagida, Toshio; Seiyama, Akitoshi

    2004-01-01

    Near-infrared spectroscopy (NIRS) was used to measure frontal regional cerebral blood volume (rCBV) in a person whose brain was under the influence of pharmacological agents while the person was performing a complex task. Fourteen healthy participants were administered Uchida-Kraepelin psychodiagnostic (UKP) tests before and after caffeine intake, and the concentration of caffeine in the urine was measured. The average number of answers and the average number of correct answers given by the participants improved significantly following caffeine intake. During the UKP testing, changes in the rCBV in the inferior frontal cortex were continuously measured using NIRS. The volume during the rest periods decreased as a result of caffeine-induced constriction of the cerebral arteriola. The volume increased during the mental work, but the degree of the increase was the same before and after caffeine intake. Although the performance of the mental work improved following caffeine intake, the improvement was not reflected in the rCBV in the inferior frontal cerebral cortex. These results suggest that caffeine helps to protect the brain from excessive hyperemia in addition to activating the neurons in the prefrontal cortex. PMID:15250767

  11. Effects of antipsychotic drugs on the expression of synapse-associated proteins in the frontal cortex of rats subjected to immobilization stress.

    PubMed

    Seo, Mi Kyoung; Lee, Chan Hong; Cho, Hye Yeon; You, Young Sun; Lee, Bong Ju; Lee, Jung Goo; Park, Sung Woo; Kim, Young Hoon

    2015-10-30

    The present study examined the effects of antipsychotic drugs on the expression of synapse-associated proteins in the frontal cortex of rats with and without immobilization stress. Rats were subjected to immobilization stress 6h/day for 3 weeks. The effects of atypical antipsychotic drugs, olanzapine and aripiprazole, on expression of serine(9)-phosphorylated GSK-3β, β-catenin, BDNF, PSD-95, and synaptophysin were determined by Western blotting. A typical antipsychotic drug, haloperidol, was used for comparison. Immobilization stress significantly decreased the expression of these proteins in the frontal cortex. Chronic administration of olanzapine and aripiprazole significantly attenuated the immobilization stress-induced decrease in the levels of these proteins, whereas haloperidol had no such effect. Additionally, olanzapine and aripiprazole significantly increased levels of phosphorylated GSK-3β under normal conditions without stress, and aripiprazole also increased BDNF levels under this condition. These results indicate that olanzapine and aripiprazole, and, haloperidol, differentially regulate the levels of synapse-associated proteins in the rat frontal cortex. These findings may contribute to explain the neurobiological basis of how olanzapine and aripiprazole up-regulated synapse-associated proteins. PMID:26254796

  12. The enhanced information flow from visual cortex to frontal area facilitates SSVEP response: evidence from model-driven and data-driven causality analysis.

    PubMed

    Li, Fali; Tian, Yin; Zhang, Yangsong; Qiu, Kan; Tian, Chunyang; Jing, Wei; Liu, Tiejun; Xia, Yang; Guo, Daqing; Yao, Dezhong; Xu, Peng

    2015-01-01

    The neural mechanism of steady-state visual evoked potentials (SSVEP) is still not clearly understood. Especially, only certain frequency stimuli can evoke SSVEP. Our previous network study reveals that 8 Hz stimulus that can evoke strong SSVEP response shows the enhanced linkage strength between frontal and visual cortex. To further probe the directed information flow between the two cortex areas for various frequency stimuli, this paper develops a causality analysis based on the inversion of double columns model using particle swarm optimization (PSO) to characterize the directed information flow between visual and frontal cortices with the intracranial rat electroencephalograph (EEG). The estimated model parameters demonstrate that the 8 Hz stimulus shows the enhanced directional information flow from visual cortex to frontal lobe facilitates SSVEP response, which may account for the strong SSVEP response for 8 Hz stimulus. Furthermore, the similar finding is replicated by data-driven causality analysis. The inversion of neural mass model proposed in this study may be helpful to provide the new causality analysis to link the physiological model and the observed datasets in neuroscience and clinical researches. PMID:26434769

  13. The enhanced information flow from visual cortex to frontal area facilitates SSVEP response: evidence from model-driven and data-driven causality analysis

    NASA Astrophysics Data System (ADS)

    Li, Fali; Tian, Yin; Zhang, Yangsong; Qiu, Kan; Tian, Chunyang; Jing, Wei; Liu, Tiejun; Xia, Yang; Guo, Daqing; Yao, Dezhong; Xu, Peng

    2015-10-01

    The neural mechanism of steady-state visual evoked potentials (SSVEP) is still not clearly understood. Especially, only certain frequency stimuli can evoke SSVEP. Our previous network study reveals that 8 Hz stimulus that can evoke strong SSVEP response shows the enhanced linkage strength between frontal and visual cortex. To further probe the directed information flow between the two cortex areas for various frequency stimuli, this paper develops a causality analysis based on the inversion of double columns model using particle swarm optimization (PSO) to characterize the directed information flow between visual and frontal cortices with the intracranial rat electroencephalograph (EEG). The estimated model parameters demonstrate that the 8 Hz stimulus shows the enhanced directional information flow from visual cortex to frontal lobe facilitates SSVEP response, which may account for the strong SSVEP response for 8 Hz stimulus. Furthermore, the similar finding is replicated by data-driven causality analysis. The inversion of neural mass model proposed in this study may be helpful to provide the new causality analysis to link the physiological model and the observed datasets in neuroscience and clinical researches.

  14. Experimentally-induced maternal hypothyroidism alters crucial enzyme activities in the frontal cortex and hippocampus of the offspring rat.

    PubMed

    Koromilas, Christos; Tsakiris, Stylianos; Kalafatakis, Konstantinos; Zarros, Apostolos; Stolakis, Vasileios; Kimpizi, Despoina; Bimpis, Alexios; Tsagianni, Anastasia; Liapi, Charis

    2015-02-01

    Thyroid hormone insufficiency during neurodevelopment can result into significant structural and functional changes within the developing central nervous system (CNS), and is associated with the establishment of serious cognitive impairment and neuropsychiatric symptomatology. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil (PTU)-induced hypothyroidism as a multilevel experimental approach to the study of hypothyroidism-induced changes on crucial brain enzyme activities of 21-day-old Wistar rat offspring in a brain region-specific manner. This experimental approach has been recently developed and characterized by the authors based on neurochemical analyses performed on newborn and 21-day-old rat offspring whole brain homogenates; as a continuum to this effort, the current study focused on two CNS regions of major significance for cognitive development: the frontal cortex and the hippocampus. Maternal exposure to PTU in the drinking water during gestation and/or lactation resulted into changes in the activities of acetylcholinesterase and two important adenosinetriphosphatases (Na(+),K(+)- and Mg(2+)-ATPase), that seemed to take place in a CNS-region-specific manner and that were dependent upon the PTU-exposure timeframe followed. As these findings are analyzed and compared to the available literature, they: (i) highlight the variability involved in the changes of the aforementioned enzymatic parameters in the studied CNS regions (attributed to both the different neuroanatomical composition and the thyroid-hormone-dependent neurodevelopmental growth/differentiation patterns of the latter), (ii) reveal important information with regards to the neurochemical mechanisms that could be involved in the way clinical hypothyroidism could affect optimal neurodevelopment and, ultimately, cognitive function, as well as (iii) underline the need for the adoption of more consistent

  15. The Effect of Retrieval Focus and Emotional Valence on the Inferior Frontal Cortex Activity during Autobiographical Recollection

    PubMed Central

    Denkova, Ekaterina; Dolcos, Sanda; Dolcos, Florin

    2013-01-01

    Although available evidence points to a role of the inferior frontal cortex (IFC) in both emotion processing and autobiographical memory (AM) recollection, it is unclear what the role of this region is in emotional AM recollection. The present study investigated whether IFC activity can be influenced by manipulations of the retrieval focus (emotional vs. non-emotional) and whether this influence is similar for AMs with positive and negative emotional valence. Participants were asked to focus either on emotional (Emotion condition) or on non-emotional contextual (Context condition) details during the elaboration of positive and negative AMs, while fMRI data were collected. The study yielded two main findings: (1) Focusing on Emotion compared to Context during AM recollection was associated with increased activity in bilateral IFC, for positive AMs, whereas negative AMs produced similarly high IFC activity during Emotion and Context conditions; (2) There was a hemispheric dissociation in the IFC linked to the experiencing of emotion and the focus of AM recollection, such that the left IFC activity correlated positively with the subjective re-experience of emotion during the Emotion condition, whereas the right IFC activity correlated negatively with the subjective re-experience of emotion during the Context condition, for both positive and negative AMs. Overall, the present findings suggest that IFC’s involvement during the recollection of emotional AMs is susceptible to manipulations of the retrieval focus only in the case of positive AMs, and that this region plays a role in both the enhancement and inhibition of emotional experience during AM recollection. PMID:24379766

  16. MicroRNA expression profiling reveals miRNA families regulating specific biological pathways in mouse frontal cortex and hippocampus.

    PubMed

    Juhila, Juuso; Sipilä, Tessa; Icay, Katherine; Nicorici, Daniel; Ellonen, Pekka; Kallio, Aleksi; Korpelainen, Eija; Greco, Dario; Hovatta, Iiris

    2011-01-01

    MicroRNAs (miRNAs) are small regulatory molecules that cause post-transcriptional gene silencing. Although some miRNAs are known to have region-specific expression patterns in the adult brain, the functional consequences of the region-specificity to the gene regulatory networks of the brain nuclei are not clear. Therefore, we studied miRNA expression patterns by miRNA-Seq and microarrays in two brain regions, frontal cortex (FCx) and hippocampus (HP), which have separate biological functions. We identified 354 miRNAs from FCx and 408 from HP using miRNA-Seq, and 245 from FCx and 238 from HP with microarrays. Several miRNA families and clusters were differentially expressed between FCx and HP, including the miR-8 family, miR-182|miR-96|miR-183 cluster, and miR-212|miR-312 cluster overexpressed in FCx and miR-34 family overexpressed in HP. To visualize the clusters, we developed support for viewing genomic alignments of miRNA-Seq reads in the Chipster genome browser. We carried out pathway analysis of the predicted target genes of differentially expressed miRNA families and clusters to assess their putative biological functions. Interestingly, several miRNAs from the same family/cluster were predicted to regulate specific biological pathways. We have developed a miRNA-Seq approach with a bioinformatic analysis workflow that is suitable for studying miRNA expression patterns from specific brain nuclei. FCx and HP were shown to have distinct miRNA expression patterns which were reflected in the predicted gene regulatory pathways. This methodology can be applied for the identification of brain region-specific and phenotype-specific miRNA-mRNA-regulatory networks from the adult and developing rodent brain. PMID:21731767

  17. Conceptual control across modalities: graded specialisation for pictures and words in inferior frontal and posterior temporal cortex

    PubMed Central

    Krieger-Redwood, Katya; Teige, Catarina; Davey, James; Hymers, Mark; Jefferies, Elizabeth

    2015-01-01

    Controlled semantic retrieval to words elicits co-activation of inferior frontal (IFG) and left posterior temporal cortex (pMTG), but research has not yet established (i) the distinct contributions of these regions or (ii) whether the same processes are recruited for non-verbal stimuli. Words have relatively flexible meanings – as a consequence, identifying the context that links two specific words is relatively demanding. In contrast, pictures are richer stimuli and their precise meaning is better specified by their visible features – however, not all of these features will be relevant to uncovering a given association, tapping selection/inhibition processes. To explore potential differences across modalities, we took a commonly-used manipulation of controlled retrieval demands, namely the identification of weak vs. strong associations, and compared word and picture versions. There were 4 key findings: (1) Regions of interest (ROIs) in posterior IFG (BA44) showed graded effects of modality (e.g., words>pictures in left BA44; pictures>words in right BA44). (2) An equivalent response was observed in left mid-IFG (BA45) across modalities, consistent with the multimodal semantic control deficits that typically follow LIFG lesions. (3) The anterior IFG (BA47) ROI showed a stronger response to verbal than pictorial associations, potentially reflecting a role for this region in establishing a meaningful context that can be used to direct semantic retrieval. (4) The left pMTG ROI also responded to difficulty across modalities yet showed a stronger response overall to verbal stimuli, helping to reconcile two distinct literatures that have implicated this site in semantic control and lexical-semantic access respectively. We propose that left anterior IFG and pMTG work together to maintain a meaningful context that shapes ongoing semantic processing, and that this process is more strongly taxed by word than picture associations. PMID:25726898

  18. A role for left inferior frontal and posterior superior temporal cortex in extracting a syntactic tree from a sentence.

    PubMed

    Pattamadilok, Chotiga; Dehaene, Stanislas; Pallier, Christophe

    2016-02-01

    On reading the sentence "the kids who exhausted their parents slept", how do we decide that it is the kids who slept and not the parents? The present behavioral and functional magnetic resonance imaging (fMRI) study explored the processes underlying the extraction of syntactically organized information from sentences. Participants were presented with sentences whose syntactic complexity was manipulated using either a center-embedded or an adjunct structure. The goal was to vary separately the sentence syntactic structure and the linear distance between the main verb and its subject. Each sentence was followed by a short subject + verb probe, and the participants had to check whether or not it matched a proposition expressed in the sentence. Behavioral and fMRI data showed a significant cost and enhanced activity within left inferior frontal and posterior superior temporal cortex whenever participants processed center-embedded sentences, which required extracting a nontrivial subtree formed by nonadjacent words. This syntactic complexity effect was not observed during online sentence processing but rather during the processing of the probe and only when the verification could not rely on a superficial lexical analysis. Moreover, the manipulation of linear distance affected performance and brain activity mainly when the sentences did not have a center-embedded structure. We did not find evidence suggesting that tree-extraction, a fundamental operation of a core syntax network, takes place during sentence comprehension. The present finding showed that the syntactic complexity effect, which is an outcome of this operation, became detectable later on, whenever we need to extract structural information not obvious in the superficial sequence of words. PMID:26709465

  19. Transcranial direct current stimulation (tDCS) of frontal cortex decreases performance on the WAIS-IV intelligence test.

    PubMed

    Sellers, Kristin K; Mellin, Juliann M; Lustenberger, Caroline M; Boyle, Michael R; Lee, Won Hee; Peterchev, Angel V; Fröhlich, Flavio

    2015-09-01

    Transcranial direct current stimulation (tDCS) modulates excitability of motor cortex. However, there is conflicting evidence about the efficacy of this non-invasive brain stimulation modality to modulate performance on cognitive tasks. Previous work has tested the effect of tDCS on specific facets of cognition and executive processing. However, no randomized, double-blind, sham-controlled study has looked at the effects of tDCS on a comprehensive battery of cognitive processes. The objective of this study was to test if tDCS had an effect on performance on a comprehensive assay of cognitive processes, a standardized intelligence quotient (IQ) test. The study consisted of two substudies and followed a double-blind, between-subjects, sham-controlled design. In total, 41 healthy adult participants were included in the final analysis. These participants completed the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV) as a baseline measure. At least one week later, participants in substudy 1 received either bilateral tDCS (anodes over both F4 and F3, cathode over Cz, 2 mA at each anode for 20 min) or active sham tDCS (2 mA for 40 s), and participants in substudy 2 received either right or left tDCS (anode over either F4 or F3, cathode over Cz, 2 mA for 20 min). In both studies, the WAIS-IV was immediately administered following stimulation to assess for performance differences induced by bilateral and unilateral tDCS. Compared to sham stimulation, right, left, and bilateral tDCS reduced improvement between sessions on Full Scale IQ and the Perceptual Reasoning Index. This demonstration that frontal tDCS selectively degraded improvement on specific metrics of the WAIS-IV raises important questions about the often proposed role of tDCS in cognitive enhancement. PMID:25934490

  20. MicroRNA Expression Profiling Reveals MiRNA Families Regulating Specific Biological Pathways in Mouse Frontal Cortex and Hippocampus

    PubMed Central

    Juhila, Juuso; Sipilä, Tessa; Icay, Katherine; Nicorici, Daniel; Ellonen, Pekka; Kallio, Aleksi; Korpelainen, Eija; Greco, Dario; Hovatta, Iiris

    2011-01-01

    MicroRNAs (miRNAs) are small regulatory molecules that cause post-transcriptional gene silencing. Although some miRNAs are known to have region-specific expression patterns in the adult brain, the functional consequences of the region-specificity to the gene regulatory networks of the brain nuclei are not clear. Therefore, we studied miRNA expression patterns by miRNA-Seq and microarrays in two brain regions, frontal cortex (FCx) and hippocampus (HP), which have separate biological functions. We identified 354 miRNAs from FCx and 408 from HP using miRNA-Seq, and 245 from FCx and 238 from HP with microarrays. Several miRNA families and clusters were differentially expressed between FCx and HP, including the miR-8 family, miR-182|miR-96|miR-183 cluster, and miR-212|miR-312 cluster overexpressed in FCx and miR-34 family overexpressed in HP. To visualize the clusters, we developed support for viewing genomic alignments of miRNA-Seq reads in the Chipster genome browser. We carried out pathway analysis of the predicted target genes of differentially expressed miRNA families and clusters to assess their putative biological functions. Interestingly, several miRNAs from the same family/cluster were predicted to regulate specific biological pathways. We have developed a miRNA-Seq approach with a bioinformatic analysis workflow that is suitable for studying miRNA expression patterns from specific brain nuclei. FCx and HP were shown to have distinct miRNA expression patterns which were reflected in the predicted gene regulatory pathways. This methodology can be applied for the identification of brain region-specific and phenotype-specific miRNA-mRNA-regulatory networks from the adult and developing rodent brain. PMID:21731767

  1. Downstream targets of methyl CpG binding protein 2 and their abnormal expression in the frontal cortex of the human Rett syndrome brain

    PubMed Central

    2010-01-01

    Background The Rett Syndrome (RTT) brain displays regional histopathology and volumetric reduction, with frontal cortex showing such abnormalities, whereas the occipital cortex is relatively less affected. Results Using microarrays and quantitative PCR, the mRNA expression profiles of these two neuroanatomical regions were compared in postmortem brain tissue from RTT patients and normal controls. A subset of genes was differentially expressed in the frontal cortex of RTT brains, some of which are known to be associated with neurological disorders (clusterin and cytochrome c oxidase subunit 1) or are involved in synaptic vesicle cycling (dynamin 1). RNAi-mediated knockdown of MeCP2 in vitro, followed by further expression analysis demonstrated that the same direction of abnormal expression was recapitulated with MeCP2 knockdown, which for cytochrome c oxidase subunit 1 was associated with a functional respiratory chain defect. Chromatin immunoprecipitation (ChIP) analysis showed that MeCP2 associated with the promoter regions of some of these genes suggesting that loss of MeCP2 function may be responsible for their overexpression. Conclusions This study has shed more light on the subset of aberrantly expressed genes that result from MECP2 mutations. The mitochondrion has long been implicated in the pathogenesis of RTT, however it has not been at the forefront of RTT research interest since the discovery of MECP2 mutations. The functional consequence of the underexpression of cytochrome c oxidase subunit 1 indicates that this is an area that should be revisited. PMID:20420693

  2. Selective reduction by isolation rearing of 5-HT1A receptor-mediated dopamine release in vivo in the frontal cortex of mice.

    PubMed

    Ago, Y; Sakaue, M; Baba, A; Matsuda, T

    2002-10-01

    Serotonin (5-HT)1A receptors modulate in vivo release of brain monoaminergic neurotransmitters which may be involved in isolation-induced aggressive behavior. The present study examined the effect of isolation rearing on the 5-HT1A receptor-mediated modulation of dopamine (DA), 5-HT and noradrenaline (NA) release in the frontal cortex of mice. The selective 5-HT1A receptor agonist (S)-5-[-[(1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-benzodioxole HCl (MKC-242) increased the release of DA and NA and decreased the release of 5-HT in the frontal cortex of mice. The effect of MKC-242 on DA release was significantly less in isolation-reared mice than in group-reared mice, while effects of the drug on NA and 5-HT release did not differ between both groups. The effect of the other 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin on cortical DA release was also less in isolation-reared mice than in group-reared mice, and that of the drug on cortical 5-HT release did not differ between both groups. In contrast to MKC-242-induced DA release, amphetamine-induced increase in cortical DA release in vivo was greater in isolation-reared mice. The present findings suggest that isolation rearing enhances the activity of cortical dopaminergic neurons and reduces selectively the 5-HT1A receptor-mediated release of DA in the cortex. PMID:12423245

  3. Functional characterization of 5-HT1D autoreceptors on the modulation of 5-HT release in guinea-pig mesencephalic raphe, hippocampus and frontal cortex.

    PubMed Central

    el Mansari, M.; Blier, P.

    1996-01-01

    1. The aims of the present study were (i) to characterize further the pharmacology of 5-HT1D autoreceptors modulating 5-HT release in guinea-pig mesencephalic raphe, hippocampus and frontal cortex; (ii) to determine whether 5-HT1D receptors in the mesencephalic raphe are located on 5-HT neurones; (iii) to determine whether 5-HT1D autoreceptors are coupled to G proteins; and (iv) to assess their sensitivity following long-term 5-HT reuptake blockade and inhibition of type-A monoamine oxidase. 2. In mesencephalic raphe, hippocampus and frontal cortex slices, the 5-HT1D/1B receptor agonist, sumatriptan and the 5-HT1 receptor agonist, 5-methoxytryptamine (5-MeOT) but not the 5-HT1B receptor agonist, CP93129, inhibited electrically the evoked release of [3H]-5-HT in a concentration-dependent manner. This effect was antagonized by the 5-HT1D/1B receptor antagonist GR127935 in the three structures, but not by the 5-HT1A receptor antagonist, (+)-WAY100635 in mesencephalic raphe slices. These results confirm the presence of functional 5-HT1D autoreceptors controlling 5-HT release within the mesencephalic raphe as well as in terminal regions. 3. The inhibitory effect of sumatriptan on K(+)-evoked release of [3H]-5-HT was not reduced by the addition of the Na+ channel blocker, tetrodotoxin to the superfusion medium, suggesting that these 5-HT1D receptors in the mesencephalic raphe are located on 5-HT neurones and may be considered autoreceptors. 4. The in vitro treatment with the alkylating agent N-ethylmaleimide (NEM) was used to determine whether these 5-HT1D autoreceptors are coupled to G proteins. The inhibitory effect of sumatriptan on electrically evoked release of [3H]-5-HT was attenuated in NEM-pretreated slices from mesencephalic raphe, hippocampus and frontal cortex, indicating that the 5-HT1D autoreceptors activated by sumatriptan are coupled to G proteins in these three structures. Taken together with our previous results, this suggests that, in addition to the 5

  4. A single dose of vortioxetine, but not ketamine or fluoxetine, increases plasticity-related gene expression in the rat frontal cortex.

    PubMed

    du Jardin, Kristian Gaarn; Müller, Heidi Kaastrup; Sanchez, Connie; Wegener, Gregers; Elfving, Betina

    2016-09-01

    Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist that has been shown to induce a rapid antidepressant effect in treatment-resistant patients. Vortioxetine is a multimodal-acting antidepressant that exert its therapeutic activity through serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibition and modulation of several 5-HT receptors. In clinical trials, vortioxetine improves depression symptoms and cognitive dysfunction. Neuroplasticity as well as serotonergic and glutamatergic signaling attain significant roles in depression pathophysiology and antidepressant responses. Here, we investigate the effects of ketamine and vortioxetine on gene expression related to serotonergic and glutamatergic neurotransmission as well as neuroplasticity and compare them to those of the selective serotonin reuptake inhibitor fluoxetine. Rats were injected with fluoxetine (10mg/kg), ketamine (15mg/kg), or vortioxetine (10mg/kg) at 2, 8, 12, or 27h prior to harvesting of the frontal cortex and hippocampus. mRNA levels were measured by real-time quantitative polymerase chain reaction (qPCR). The main finding was that vortioxetine enhanced plasticity-related gene expression (Mtor, Mglur1, Pkcα, Homer3, Spinophilin, and Synapsin3) in the frontal cortex at 8h after a single dose. Ingenuity pathway analysis of this subset of data identified a biological network that was engaged by vortioxetine and is plausibly associated with neuroplasticity. Transcript levels had returned to baseline levels 12h after injection. Only minor effects on gene expression were found for ketamine or fluoxetine. In conclusion, acute vortioxetine, but not fluoxetine or ketamine, transiently increased plasticity-related gene expression in the frontal cortex. These effects may be ascribed to the direct 5-HT receptor activities of vortioxetine. PMID:27235984

  5. Cocaine-induced Fos expression is detectable in the frontal cortex and striatum of rats under isoflurane but not α-chloralose anesthesia: implications for FMRI

    PubMed Central

    Kufahl, Peter R.; Pentkowski, Nathan S.; Heintzelman, Krista; Neisewander, Janet L.

    2009-01-01

    The ability of intravenous cocaine to induce Fos protein expression in anesthetized rats was tested. Two anesthetic regimens commonly used for in vivo FMRI of animals, i.v. α-chloralose and gaseous isoflurane, were studied in separate cohorts. The first experiment included three groups that received the following treatments: saline i.v. and no anesthetic; 2 mg/kg cocaine i.v. and no anesthetic; and 2 mg/kg cocaine i.v. under 36 mg/kg/h α-chloralose anesthesia. The second experiment had a factorial design of four groups that were either nonanesthetized or isoflurane-treated and were either given saline or cocaine (2 mg/kg, i.v.). Anesthetized rats were maintained for 2 h under 2.5–3.5% isoflurane anesthesia, while nonanesthetized rats were kept in an alternative environment for the same time period. Rats were given 2 mg/kg cocaine or saline i.v., 30 min into the test session. Rats were perfused and their brains were processed for Fos immunohistochemistry 90 min after the i.v. treatment. In both experiments, the frontal cortex and striatum of the cocaine-treated nonanesthetized rats expressed Fos in greater amounts than the saline-treated nonanesthetized rats, as expected. The α-chloralose treatment prevented cocaine-induced Fos expression across all eight subregions of the striatum and frontal cortex that were examined. In contrast, isoflurane only partially attenuated Fos expression in the orbital and Cg2 subregions of frontal cortex. These results suggest a strong advantage for using isoflurane, as opposed to α-chloralose, when studying anesthetized rats for in vivo effects of psychostimulants. PMID:19467261

  6. Cocaine-induced Fos expression is detectable in the frontal cortex and striatum of rats under isoflurane but not alpha-chloralose anesthesia: implications for FMRI.

    PubMed

    Kufahl, Peter R; Pentkowski, Nathan S; Heintzelman, Krista; Neisewander, Janet L

    2009-07-30

    The ability of intravenous cocaine to induce Fos protein expression in anesthetized rats was tested. Two anesthetic regimens commonly used for in vivo FMRI of animals, i.v. alpha-chloralose and gaseous isoflurane, were studied in separate cohorts. The first experiment included three groups that received the following treatments: saline i.v. and no anesthetic; 2 mg/kg cocaine i.v. and no anesthetic; and 2mg/kg cocaine i.v. under 36 mg/kg/h alpha-chloralose anesthesia. The second experiment had a factorial design of four groups that were either nonanesthetized or isoflurane-treated and were either given saline or cocaine (2 mg/kg, i.v.). Anesthetized rats were maintained for 2 h under 2.5-3.5% isoflurane anesthesia, while nonanesthetized rats were kept in an alternative environment for the same time period. Rats were given 2 mg/kg cocaine or saline i.v., 30 min into the test session. Rats were perfused and their brains were processed for Fos immunohistochemistry 90 min after the i.v. treatment. In both experiments, the frontal cortex and striatum of the cocaine-treated nonanesthetized rats expressed Fos in greater amounts than the saline-treated nonanesthetized rats, as expected. The alpha-chloralose treatment prevented cocaine-induced Fos expression across all eight subregions of the striatum and frontal cortex that were examined. In contrast, isoflurane only partially attenuated Fos expression in the orbital and Cg2 subregions of frontal cortex. These results suggest a strong advantage for using isoflurane, as opposed to alpha-chloralose, when studying anesthetized rats for in vivo effects of psychostimulants. PMID:19467261

  7. Laser ablation-inductively coupled plasma-mass spectrometry imaging of white and gray matter iron distribution in Alzheimer's disease frontal cortex.

    PubMed

    Hare, Dominic J; Raven, Erika P; Roberts, Blaine R; Bogeski, Mirjana; Portbury, Stuart D; McLean, Catriona A; Masters, Colin L; Connor, James R; Bush, Ashley I; Crouch, Peter J; Doble, Philip A

    2016-08-15

    Iron deposition in the brain is a feature of normal aging, though in several neurodegenerative disorders, including Alzheimer's disease, the rate of iron accumulation is more advanced than in age-matched controls. Using laser ablation-inductively coupled plasma-mass spectrometry imaging we present here a pilot study that quantitatively assessed the iron content of white and gray matter in paraffin-embedded sections from the frontal cortex of Alzheimer's and control subjects. Using the phosphorus image as a confirmed proxy for the white/gray matter boundary, we found that increased intrusion of iron into gray matter occurs in the Alzheimer's brain compared to controls, which may be indicative of either a loss of iron homeostasis in this vulnerable brain region, or provide evidence of increased inflammatory processes as a response to chronic neurodegeneration. We also observed a trend of increasing iron within the white matter of the frontal cortex, potentially indicative of disrupted iron metabolism preceding loss of myelin integrity. Considering the known potential toxicity of excessive iron in the brain, our results provide supporting evidence for the continuous development of novel magnetic resonance imaging approaches for assessing white and gray matter iron accumulation in Alzheimer's disease. PMID:27233149

  8. Role of the Frontal Cortex in Standing Postural Sway Tasks While Dual-Tasking: A Functional Near-Infrared Spectroscopy Study Examining Working Memory Capacity

    PubMed Central

    Fujita, Hiroyuki; Kasubuchi, Kenji; Wakata, Satoshi; Hiyamizu, Makoto; Morioka, Shu

    2016-01-01

    Posture control during a dual-task involves changing the distribution of attention resources between the cognitive and motor tasks and involves the frontal cortex working memory (WM). The present study aimed to better understand the impact of frontal lobe activity and WM capacity in postural control during a dual-task. High and low WM-span groups were compared using their reading span test scores. High and low WM capacity were compared based on cognitive and balance performance and hemoglobin oxygenation (oxyHb) levels during standing during single (S-S), standing during dual (S-D), one leg standing during single (O-S), and one leg standing during dual (O-D) tasks. For sway pass length, significant difference in only the O-D task was observed between both groups. oxyHb levels were markedly increased in the right dorsolateral prefrontal cortex and supplementary motor area in the high-span group during a dual-task. Therefore, WM capacity influenced the allocation of attentional resources and motor performance. PMID:27034947

  9. Role of the Frontal Cortex in Standing Postural Sway Tasks While Dual-Tasking: A Functional Near-Infrared Spectroscopy Study Examining Working Memory Capacity.

    PubMed

    Fujita, Hiroyuki; Kasubuchi, Kenji; Wakata, Satoshi; Hiyamizu, Makoto; Morioka, Shu

    2016-01-01

    Posture control during a dual-task involves changing the distribution of attention resources between the cognitive and motor tasks and involves the frontal cortex working memory (WM). The present study aimed to better understand the impact of frontal lobe activity and WM capacity in postural control during a dual-task. High and low WM-span groups were compared using their reading span test scores. High and low WM capacity were compared based on cognitive and balance performance and hemoglobin oxygenation (oxyHb) levels during standing during single (S-S), standing during dual (S-D), one leg standing during single (O-S), and one leg standing during dual (O-D) tasks. For sway pass length, significant difference in only the O-D task was observed between both groups. oxyHb levels were markedly increased in the right dorsolateral prefrontal cortex and supplementary motor area in the high-span group during a dual-task. Therefore, WM capacity influenced the allocation of attentional resources and motor performance. PMID:27034947

  10. Adolescent testosterone influences BDNF and TrkB mRNA and neurotrophin-interneuron marker relationships in mammalian frontal cortex.

    PubMed

    Purves-Tyson, Tertia D; Allen, Katherine; Fung, Samantha; Rothmond, Debora; Noble, Pam L; Handelsman, David J; Shannon Weickert, Cynthia

    2015-11-01

    Late adolescence in males is a period of increased susceptibility for the onset of schizophrenia, coinciding with increased circulating testosterone. The cognitive deficits prevalent in schizophrenia may be related to unhealthy cortical interneurons, which are trophically dependent on brain derived neurotrophic factor. We investigated, under conditions of depleted (monkey and rat) and replaced (rat) testosterone over adolescence, changes in gene expression of cortical BDNF and TrkB transcripts and interneuron markers and the relationships between these mRNAs and circulating testosterone. Testosterone removal by gonadectomy reduced gene expression of some BDNF transcripts in monkey and rat frontal cortices and the BDNF mRNA reduction was prevented by testosterone replacement. In rat, testosterone replacement increased the potential for classical TrkB signalling by increasing the full length to truncated TrkB mRNA ratio, whereas in the monkey cortex, circulating testosterone was negatively correlated with the TrkB full length/truncated mRNA ratio. We did not identify changes in interneuron gene expression in monkey frontal cortex in response to gonadectomy, and in rat, we showed that only somatostatin mRNA was decreased by gonadectomy but not restored by testosterone replacement. We identified complex and possibly species-specific, relationships between BDNF/TrkB gene expression and interneuron marker gene expression that appear to be dependent on the presence of testosterone at adolescence in rat and monkey frontal cortices. Taken together, our findings suggest there are dynamic relationships between BDNF/TrkB and interneuron markers that are dependent on the presence of testosterone but that this may not be a straightforward increase in testosterone leading to changes in BDNF/TrkB that contributes to interneuron health. PMID:26088421

  11. Dopamine receptor signaling in the medial orbital frontal cortex and the acquisition and expression of fructose-conditioned flavor preferences in rats

    PubMed Central

    Malkusz, Danielle C.; Yenko, Ira; Rotella, Francis M.; Banakos, Theodore; Olsson, Kerstin; Dindyal, Trisha; Vig, Vishal; Bodnar, Richard J.

    2014-01-01

    Systemic dopamine (DA) D1 (SCH23390: SCH) and D2 (raclopride: RAC) antagonists blocked fructose-conditioned flavor preference (CFP) acquisition and expression. Fructose-CFP acquisition was eliminated by medial prefrontal cortex (mPFC) SCH and mPFC or amygdala (AMY) RAC. Fructose-CFP expression was reduced following SCH or RAC in AMY or nucleus accumbens (NAc). The present study examined fructose-CFP acquisition and expression following SCH and RAC in the medial orbital frontal cortex (MOFC), another ventral tegmental area DA target. For fructose-CFP acquisition, five groups of rats received vehicle, SCH (24 or 48 nmol) or RAC (24 or 48 nmol) in the MOFC 0.5 h prior to 8 training sessions with one flavor (CS+/Fs) mixed in 8% fructose and 0.2% saccharin, and another flavor (CS-/s) mixed in 0.2% saccharin. In six 2-bottle choice tests in 0.2% saccharin, similar fructose-CFP preferences occurred in groups trained with vehicle (76–77%), SCH24 (69–78%), SCH48(70–74%) and RAC48 (85–92%). RAC24-trained rats displayed significant CS+ preferences during the first (79%) and third (71%), but not second (58%) test pair. For fructose-CFP expression, rats similarly trained with CS+/Fs and CS- solutions received 2-bottle choice tests following MOFC injections of SCH or RAC (12–48 nmol). CS+ preference expression was significantly reduced by RAC (48 nmol: 58%), but not SCH relative to vehicle (78%). A control group receiving RAC in the dorsolateral prefrontal cortex displayed fructose-CFP expression similar to vehicle. These data demonstrate differential frontal cortical DA mediation of fructose-CFP with mPFC D1 and D2 signaling exclusively mediating acquisition, and MOFC D2 signaling primarily mediating expression. PMID:25446441

  12. 5-HT2A Receptor Binding in the Frontal Cortex of Parkinson's Disease Patients and Alpha-Synuclein Overexpressing Mice: A Postmortem Study

    PubMed Central

    Rasmussen, Nadja Bredo; Olesen, Mikkel Vestergaard; Plenge, Per; Klein, Anders Bue; Westin, Jenny E.; Fog, Karina

    2016-01-01

    The 5-HT2A receptor is highly involved in aspects of cognition and executive function and seen to be affected in neurodegenerative diseases like Alzheimer's disease and related to the disease pathology. Even though Parkinson's disease (PD) is primarily a motor disorder, reports of impaired executive function are also steadily being associated with this disease. Not much is known about the pathophysiology behind this. The aim of this study was thereby twofold: (1) to investigate 5-HT2A receptor binding levels in Parkinson's brains and (2) to investigate whether PD associated pathology, alpha-synuclein (AS) overexpression, could be associated with 5-HT2A alterations. Binding density for the 5-HT2A-specific radioligand [3H]-MDL 100.907 was measured in membrane suspensions of frontal cortex tissue from PD patients. Protein levels of AS were further measured using western blotting. Results showed higher AS levels accompanied by increased 5-HT2A receptor binding in PD brains. In a separate study, we looked for changes in 5-HT2A receptors in the prefrontal cortex in 52-week-old transgenic mice overexpressing human AS. We performed region-specific 5-HT2A receptor binding measurements followed by gene expression analysis. The transgenic mice showed lower 5-HT2A binding in the frontal association cortex that was not accompanied by changes in gene expression levels. This study is one of the first to look at differences in serotonin receptor levels in PD and in relation to AS overexpression. PMID:27579212

  13. 5-HT2A Receptor Binding in the Frontal Cortex of Parkinson's Disease Patients and Alpha-Synuclein Overexpressing Mice: A Postmortem Study.

    PubMed

    Rasmussen, Nadja Bredo; Olesen, Mikkel Vestergaard; Brudek, Tomasz; Plenge, Per; Klein, Anders Bue; Westin, Jenny E; Fog, Karina; Wörtwein, Gitta; Aznar, Susana

    2016-01-01

    The 5-HT2A receptor is highly involved in aspects of cognition and executive function and seen to be affected in neurodegenerative diseases like Alzheimer's disease and related to the disease pathology. Even though Parkinson's disease (PD) is primarily a motor disorder, reports of impaired executive function are also steadily being associated with this disease. Not much is known about the pathophysiology behind this. The aim of this study was thereby twofold: (1) to investigate 5-HT2A receptor binding levels in Parkinson's brains and (2) to investigate whether PD associated pathology, alpha-synuclein (AS) overexpression, could be associated with 5-HT2A alterations. Binding density for the 5-HT2A-specific radioligand [(3)H]-MDL 100.907 was measured in membrane suspensions of frontal cortex tissue from PD patients. Protein levels of AS were further measured using western blotting. Results showed higher AS levels accompanied by increased 5-HT2A receptor binding in PD brains. In a separate study, we looked for changes in 5-HT2A receptors in the prefrontal cortex in 52-week-old transgenic mice overexpressing human AS. We performed region-specific 5-HT2A receptor binding measurements followed by gene expression analysis. The transgenic mice showed lower 5-HT2A binding in the frontal association cortex that was not accompanied by changes in gene expression levels. This study is one of the first to look at differences in serotonin receptor levels in PD and in relation to AS overexpression. PMID:27579212

  14. Disrupted Reinforcement Signaling in Orbital Frontal Cortex and Caudate in Youths with Conduct Disorder/Oppositional Defiant Disorder and High Psychopathic Traits

    PubMed Central

    Finger, Elizabeth C.; Marsh, Abigail A.; Blair, Karina S.; Reid, Marguerite. E.; Sims, Courtney; Ng, Pamela; Pine, Daniel S.; Blair, R. James. R.

    2010-01-01

    OBJECTIVE Dysfunction in amygdala and orbital frontal cortex functioning has been reported in youths and adults with psychopathic traits. However, the specific nature of the computational irregularities within these brain structures remains poorly understood. The current study used the passive avoidance task to examine responsiveness of these systems to early stimulus-reinforcement exposure, when prediction errors are greatest and learning maximized, and to reward in youths with psychopathic traits and comparison youths. METHOD 30 youths (N=15 with conduct disorder or oppositional defiant disorder plus high psychopathic traits and N=15 comparison subjects) completed a 3.0 T fMRI scan while performing a passive avoidance learning task. RESULTS Relative to comparison youth, youths with conduct disorder or oppositional defiant disorder plus psychopathic traits showed reduced orbitofrontal cortex responsiveness both to early stimulus-reinforcement exposure and to rewards, as well as reduced caudate response to early stimulus-reinforcement exposure. Contrary to other predictions, however, there were no group differences in amygdala responsiveness specifically to these two task parameters. However, amygdala responsiveness throughout the task was reduced in the youths with conduct disorder or oppositional defiant disorder plus psychopathic traits. CONCLUSIONS This study demonstrates that youths with conduct disorder or oppositional defiant disorder plus psychopathic traits are marked by a compromised sensitivity to early reinforcement information in both orbitofrontal cortex and caudate and to reward outcome information within orbitofrontal cortex. They further suggest that the integrated functioning of the amygdala, caudate and orbitofrontal cortex may be disrupted in individuals with this disorder. PMID:21078707

  15. Characterization of sulpipride-displaceable sup 3 H-YM-09151-2 binding sites in rat frontal cortex and the effects of subchronic treatment with haloperidol on cortical D-2 dopamine receptors

    SciTech Connect

    Kazawa, Tetsushi; Higuchi, Teruhiko National Institute of Neuroscience, Tokyo ); Mikuni, Masahiko; Takahshi, Kiyohisa ); Arai, Ichiro; Yamauchi, Toshio )

    1990-01-01

    We investigated the pharmacological properties of the sulpiride-displaceable binding sites labeled by {sup 3}H-YM-09151-2 in rat frontal cortex, compared to those in striatum. The IC{sub 50} value of ketanserin was 486 nM, which was apparently different from its affinity for the 5HT-2 receptor. Various dopamine antagonists showed almost the same inhibitory effects for binding site in frontal cortex and striatum. Sulpiride-displaceable {sup 3}H-YM-09151-2 binding sites were considered to be D-2 dopamine receptors. After subchronic treatment with haloperidol, the D-2 receptor density of frontal cortex increased to the same extent as striatum without significant change in apparent affinity.

  16. Abnormal Expression of the GIRK2 Potassium Channel in Hippocampus, Frontal Cortex and Substantia Nigra of Ts65Dn Mouse: A Model of Down Syndrome

    PubMed Central

    Harashima, Chie; Jacobowitz, David M.; Witta, Jassir; Borke, Rosemary C.; Best, Tyler K.; Siarey, Richard J.; Galdzicki, Zygmunt

    2010-01-01

    Ts65Dn, a mouse model of Down syndrome (DS), demonstrates abnormal hippocampal synaptic plasticity and behavioral abnormalities related to spatial learning and memory. The molecular mechanisms leading to these impairments have not been identified. In this study, we focused on the G-protein-activated inwardly rectifying potassium channel 2 (GIRK2) gene that is highly expressed in the hippocampus region. We studied the expression pattern of GIRK subunits in Ts65Dn and found that GIRK2 was over-expressed in all analyzed Ts65Dn brain regions. Interestingly elevated levels of GIRK2 protein in the Ts65Dn hippocampus and frontal cortex correlated with elevated levels of GIRK1 protein. This suggests that heteromeric GIRK1-GIRK2 channels are over-expressed in Ts65Dn hippocampus and frontal cortex, which could impair excitatory input, modulate spike frequency and synaptic kinetics in the affected regions. All GIRK2 splicing isoforms examined were expressed at higher levels in the Ts65Dn in comparison to the diploid hippocampus. The pattern of GIRK2 expression in the Ts65Dn mouse brain revealed by in situ hybridization and immunohistochemistry was similar to that previously reported in the rodent brain. However, in the Ts65Dn mouse a strong immunofluorescent staining of GIRK2 was detected in the lacunosum molecular layer of the CA3 area of the hippocampus. In addition, tyrosine hydroxylase containing dopaminergic neurons that co-express GIRK2 were more numerous in the substantia nigra compacta and ventral tegmental area in the Ts65Dn compared to diploid controls. In summary, the regional localization and the increased brain levels coupled with known function of the GIRK channel may suggest an important contribution of GIRK2 containing channels to Ts65Dn and thus to DS neurophysiological phenotypes. PMID:16374808

  17. Effects of lisdexamfetamine alone and in combination with s-citalopram on acetylcholine and histamine efflux in the rat pre-frontal cortex and ventral hippocampus.

    PubMed

    Hutson, Peter H; Heins, Mariette S; Folgering, Joost H A

    2015-08-01

    Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by poor attention, impulse control and hyperactivity. A significant proportion of ADHD patients are also co-morbid for other psychiatric problems including mood disorders and these patients may be managed with a combination of psychostimulants and anti-depressants. While it is generally accepted that enhanced catecholamine signalling via the action of psychostimulants is likely responsible for the cognitive improvement in ADHD, other neurotransmitters including acetylcholine and histamine may be involved. In the present study, we have examined the effect of lisdexamfetamine dimesylate (LDX), an amphetamine pro-drug that is approved for the treatment of ADHD on acetylcholine and histamine efflux in pre-frontal cortex and hippocampus alone and in combination with the anti-depressant s-citalopram. LDX increased cortical acetylcholine efflux, an effect that was not significantly altered by co-administration of s-citalopram. Cortical and hippocampal histamine were markedly increased by LDX, an effect that was attenuated in the hippocampus but not in pre-frontal cortex when co-administered with s-citalopram. Taken together, these results suggest that efflux of acetylcholine and histamine may be involved in the therapeutic effects of LDX and are differentially influenced by the co-administration of s-citalopram. Attention deficit hyperactivity disorder (ADHD) is characterized by poor attention, impulse control and hyperactivity. Some ADHD patients are also co-morbid for mood disorders and may be managed with psychostimulants (e.g. lisdexamfetamine, LDX) and anti-depressants (e.g. s-citalopram). LDX increased the efflux of acetylcholine and histamine, neurotransmitters involved in cognitive function, which were differentially influenced when co-administered with s-citalopram. Acetylcholine and histamine may be involved in the therapeutic effects of LDX and are differentially

  18. The typical development of posterior medial frontal cortex function and connectivity during task control demands in youth 8-19years old.

    PubMed

    Liu, Yanni; Angstadt, Mike; Taylor, Stephan F; Fitzgerald, Kate D

    2016-08-15

    To characterize the development of neural substrate for interference processing and task control, this study examined both linear and non-linear effects of age on activation and connectivity during an interference task designed to engage the posterior medial frontal cortex (pMFC). Seventy-two youth, ages 8-19years, performed the Multi-Source Interference Task (MSIT) during functional magnetic resonance imaging (fMRI). With increasing age, overall performance across high-interference incongruent and low-interference congruent trials became faster and more accurate. Effects of age on activation to interference- (incongruent versus congruent conditions), error- (errors versus correct trials during the incongruent condition) and overall task-processing (incongruent plus congruent conditions, relative to implicit baseline) were tested in whole-brain voxel-wise analyses. Age differentially impacted activation to overall task processing in discrete sub-regions of the pMFC: activation in the pre-supplementary motor area (pre-SMA) decreased with age, whereas activation in the dorsal anterior cingulate cortex (dACC) followed a non-linear (i.e., U-shaped) pattern in relation to age. In addition, connectivity of pre-SMA with anterior insula/frontal operculum (AI/FO) increased with age. These findings suggest differential development of pre-SMA and dACC sub-regions within the pMFC. Moreover, as children age, decreases in pre-SMA activation may couple with increases in pre-SMA-AI/FO connectivity to support gains in processing speed in response to demands for task control. PMID:27173761

  19. Effects of developmental alcohol exposure vs. intubation stress on BDNF and TrkB expression in the hippocampus and frontal cortex of neonatal rats

    PubMed Central

    Boschen, K.E.; Criss, K.J.; Palamarchouk, V.; Roth, T.L.; Klintsova, A.Y.

    2015-01-01

    Third trimester-equivalent alcohol exposure causes significant deficits in hippocampal and cortical neuroplasticity, resulting in alterations to dendritic arborization, hippocampal adult neurogenesis, and performance on learning tasks. The current study investigated the impact of neonatal alcohol exposure (postnatal days 4–9, 5.25 g/kg/day) on expression of brain-derived neurotrophic factor (BDNF) and the tropomyosin-related kinase B (TrkB) receptor in the hippocampal and frontal cortex of infant Long-Evans rats. Levels of BDNF protein were increased in the hippocampus, but not frontal cortex, of alcohol-exposed rats 24 hrs after the last dose, when compared with undisturbed (but not sham-intubated) control animals. BDNF protein levels showed a trend towards increase in hippocampus of sham-intubated animals as well, suggesting an effect of the intubation procedure. TrkB protein was increased in the hippocampus of alcohol-exposed animals compared to sham-intubated pups, indicating an alcohol-specific effect on receptor expression. In addition, expression of bdnf total mRNA in alcohol-exposed and sham-intubated pups was enhanced in the hippocampus; however, there was a differential effect of alcohol and intubation stress on exon I- and IV-specific mRNA transcripts. Further, plasma corticosterone was found to be increased in both alcohol-exposed and sham-intubated pups compared to undisturbed animals. Upregulation of BDNF could potentially represent a neuroprotective mechanism activated following alcohol exposure or stress. The results suggest that alcohol exposure and stress have both overlapping and unique effects on BDNF, and highlight the need for the stress of intubation to be taken into consideration in studies that implement this route of drug delivery. PMID:25805052

  20. Effects of developmental alcohol exposure vs. intubation stress on BDNF and TrkB expression in the hippocampus and frontal cortex of neonatal rats.

    PubMed

    Boschen, K E; Criss, K J; Palamarchouk, V; Roth, T L; Klintsova, A Y

    2015-06-01

    Third trimester-equivalent alcohol exposure causes significant deficits in hippocampal and cortical neuroplasticity, resulting in alterations to dendritic arborization, hippocampal adult neurogenesis, and performance on learning tasks. The current study investigated the impact of neonatal alcohol exposure (postnatal days 4-9, 5.25 g/kg/day) on expression of brain-derived neurotrophic factor (BDNF) and the tropomyosin-related kinase B (TrkB) receptor in the hippocampal and frontal cortex of infant Long-Evans rats. Levels of BDNF protein were increased in the hippocampus, but not frontal cortex, of alcohol-exposed rats 24h after the last dose, when compared with undisturbed (but not sham-intubated) control animals. BDNF protein levels showed a trend toward increase in hippocampus of sham-intubated animals as well, suggesting an effect of the intubation procedure. TrkB protein was increased in the hippocampus of alcohol-exposed animals compared to sham-intubated pups, indicating an alcohol-specific effect on receptor expression. In addition, expression of bdnf total mRNA in alcohol-exposed and sham-intubated pups was enhanced in the hippocampus; however, there was a differential effect of alcohol and intubation stress on exon I- and IV-specific mRNA transcripts. Further, plasma corticosterone was found to be increased in both alcohol-exposed and sham-intubated pups compared to undisturbed animals. Upregulation of BDNF could potentially represent a neuroprotective mechanism activated following alcohol exposure or stress. The results suggest that alcohol exposure and stress have both overlapping and unique effects on BDNF, and highlight the need for the stress of intubation to be taken into consideration in studies that implement this route of drug delivery. PMID:25805052

  1. Alteration in Nuclear Factor-KappaB Pathway and Functionality of Estrogen via Receptors Promote Neuroinflammation in Frontal Cortex after 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Treatment

    PubMed Central

    Mitra, Soham; Ghosh, Nabanita; Sinha, Priyobrata; Chakrabarti, Nilkanta; Bhattacharyya, Arindam

    2015-01-01

    The MPTP mediated neurodegeneration in substantia nigra has been well studied, but not the status of frontal cortex. The novelty of the present study is to explore the sex difference of frontal cortex during MPTP intoxication and to investigate the role of estrogen and its receptors in presence of glial cells in a time chase experiment; to identify which pathway of NF-kappaB exist to proceed the neuroinflammation; to investigate the estrogen binding with its nuclear or cytosolic receptors and whether any direct relation exists between estrogen receptor (ER) -beta and NF-kappaB molecules p65 and RelB. The progression of neurodegeneration occurred with the association of glial cells and functional (via its nuclear and cytosolic receptors) estrogen level. Both the canonical and/or non canonical pathways of NF-kappaB exist in frontal cortex of both the sexes after MPTP treatment. The homodimeric or heterodimeric form of ER-beta binds with NF-kappaB molecules p65 and RelB differently, but the canonical or non canonical pathways of NF-kappaB molecules could not be stopped or may be promoted. The changes in the molecular and cellular pattern in frontal cortex of both sexes during MPTP intoxication depends on the estrogen function via its nuclear or cytosolic estrogen receptors. PMID:26365888

  2. A volumetric comparison of the insular cortex and its subregions in primates

    PubMed Central

    Bauernfeind, Amy L.; de Sousa, Alexandra A.; Avasthi, Tanvi; Dobson, Seth D.; Raghanti, Mary Ann; Lewandowski, Albert H.; Zilles, Karl; Semendeferi, Katerina; Allman, John M.; (Bud) Craig, Arthur D.; Hof, Patrick R.; Sherwood, Chet C.

    2013-01-01

    The neuronal composition of the insula in primates displays a gradient, transitioning from granular neocortex in the posterior-dorsal insula to agranular neocortex in the anterior-ventral insula with an intermediate zone of dysgranularity. Additionally, apes and humans exhibit a distinctive subdomain in the agranular insula, the frontoinsular cortex (FI), defined by the presence of clusters of von Economo neurons (VENs). Studies in humans indicate that the ventral anterior insula, including agranular insular cortex and FI, is involved in social awareness, and that the posterodorsal insula, including granular and dysgranular cortices, produces an internal representation of the body’s homeostatic state. We examined the volumes of these cytoarchitectural areas of insular cortex in 30 primate species, including the volume of FI in apes and humans. Results indicate that the whole insula scales hyperallometrically (exponent = 1.13) relative to total brain mass, and the agranular insula (including FI) scales against total brain mass with even greater positive allometry (exponent = 1.23), providing a potential neural basis for enhancement of social cognition in association with increased brain size. The relative volumes of the subdivisions of the insular cortex, after controlling for total brain volume, are not correlated with species typical social group size. Although its size is predicted by primate-wide allometric scaling patterns, we found that the absolute volume of the left and right agranular insula and left FI are among the most differentially expanded of the human cerebral cortex compared to our closest living relative, the chimpanzee. PMID:23466178

  3. A Combined Metabonomic and Proteomic Approach Identifies Frontal Cortex Changes in a Chronic Phencyclidine Rat Model in Relation to Human Schizophrenia Brain Pathology

    PubMed Central

    Wesseling, Hendrik; Chan, Man K; Tsang, T M; Ernst, Agnes; Peters, Fabian; Guest, Paul C; Holmes, Elaine; Bahn, Sabine

    2013-01-01

    Current schizophrenia (SCZ) treatments fail to treat the broad range of manifestations associated with this devastating disorder. Thus, new translational models that reproduce the core pathological features are urgently needed to facilitate novel drug discovery efforts. Here, we report findings from the first comprehensive label-free liquid-mass spectrometry proteomic- and proton nuclear magnetic resonance-based metabonomic profiling of the rat frontal cortex after chronic phencyclidine (PCP) intervention, which induces SCZ-like symptoms. The findings were compared with results from a proteomic profiling of post-mortem prefrontal cortex from SCZ patients and with relevant findings in the literature. Through this approach, we identified proteomic alterations in glutamate-mediated Ca2+ signaling (Ca2+/calmodulin-dependent protein kinase II, PPP3CA, and VISL1), mitochondrial function (GOT2 and PKLR), and cytoskeletal remodeling (ARP3). Metabonomic profiling revealed changes in the levels of glutamate, glutamine, glycine, pyruvate, and the Ca2+ regulator taurine. Effects on similar pathways were also identified in the prefrontal cortex tissue from human SCZ subjects. The discovery of similar but not identical proteomic and metabonomic alterations in the chronic PCP rat model and human brain indicates that this model recapitulates only some of the molecular alterations of the disease. This knowledge may be helpful in understanding mechanisms underlying psychosis, which, in turn, can facilitate improved therapy and drug discovery for SCZ and other psychiatric diseases. Most importantly, these molecular findings suggest that the combined use of multiple models may be required for more effective translation to studies of human SCZ. PMID:23942359

  4. β2-adrenoceptor stimulation restores frontal cortex plasticity and improves visuospatial performance in hidden-prenatally-malnourished young-adult rats.

    PubMed

    Sáez-Briones, Patricio; Soto-Moyano, Rubén; Burgos, Héctor; Castillo, Amparo; Valladares, Luis; Morgan, Carlos; Pérez, Hernán; Barra, Rafael; Constandil, Luis; Laurido, Claudio; Hernández, Alejandro

    2015-03-01

    Moderate reduction in dietary protein composition of pregnant rats from 25% to 8% casein, calorically compensated by carbohydrates, has been described as a "hidden malnutrition" because it does not alter body and brain weights of pups at birth. However, this dietary treatment leads to altered central noradrenergic systems, impaired cortical long-term potentiation (LTP) and worsened visuo-spatial memory performance. Given the increasing interest on the role played by β2-adrenoceptors (β2-ARs) on brain plasticity, the present study aimed to address the following in hidden-malnourished and eutrophic control rats: (i) the expression levels of β2-ARs in the frontal cortex determined by immunohistochemistry, and (ii) the effect of the β2 selective agonist clenbuterol on both LTP elicited in vivo in the prefrontal cortex and visuospatial performance measured in an eight-arm radial maze. Our results showed that, prenatally malnourished rats exhibited a significant reduction of neocortical β2-AR expression in adulthood. Concomitantly, they were unable to elicit and maintain prefrontal cortex LTP and exhibited lower visuospatial learning performance. Administration of clenbuterol (0.019, 0.038 and 0.075 mg/kg i.p.) enhanced LTP in malnourished and control animals and restored visuospatial learning performance in malnourished but not in normal rats, in a dose-dependent manner. The results suggest that decreased density of neocortical β2-ARs during postnatal life, subsequent to hidden prenatal malnutrition might affect some synaptic networks required to elicit neocortical LTP and form visuospatial memory, since those neuroplastic deficits were counteracted by β2-AR stimulation. PMID:25464009

  5. Global resting-state fMRI analysis identifies frontal cortex, striatal, and cerebellar dysconnectivity in obsessive-compulsive disorder

    PubMed Central

    Anticevic, Alan; Hu, Sien; Zhang, Sheng; Savic, Aleksandar; Billingslea, Eileen; Wasylink, Suzanne; Repovs, Grega; Cole, Michael W.; Bednarski, Sarah; Krystal, John H.; Bloch, Michael H.; Li, Chiang-shan R.; Pittenger, Christopher

    2013-01-01

    Background Obsessive-compulsive disorder (OCD) is associated with regional hyperactivity in cortico-striatal circuits. However, the large-scale patterns of abnormal neural connectivity remain uncharacterized. Resting-state functional connectivity (rs-fcMRI) studies have shown altered connectivity within the implicated circuitry, but they have used seed-driven approaches wherein a circuit of interest is defined a priori. This limits their ability to identify network abnormalities beyond the prevailing framework. This limitation is particularly problematic within the prefrontal cortex (PFC), which is large and heterogeneous and where a priori specification of seeds is therefore difficult. A hypothesis-neutral data-driven approach to the analysis of connectivity is vital. Method We analyzed rs-fcMRI data collected at 3T in 27 OCD patients and 66 matched controls using a recently developed data-driven global brain connectivity (GBC) method, both within the PFC and across the whole brain. Results We found clusters of decreased connectivity in the left lateral PFC in both whole-brain and PFC-restricted analyses. Increased GBC was found in the right putamen and left cerebellar cortex. Within ROIs in the basal ganglia and thalamus, we identified increased GBC in dorsal striatum and anterior thalamus, which was reduced in patients on medication. The ventral striatum/nucleus accumbens exhibited decreased global connectivity, but increased connectivity specifically with the ventral anterior cingulate cortex in subjects with OCD. Conclusion These findings identify previously uncharacterized PFC and basal ganglia dysconnectivity in OCD and reveal differentially altered GBC in dorsal and ventral striatum. Results highlight complex disturbances in PFC networks, which could contribute to disrupted cortical-striatal-cerebellar circuits in OCD. PMID:24314349

  6. Frontal cortex and hippocampus neurotransmitter receptor complex level parallels spatial memory performance in the radial arm maze.

    PubMed

    Shanmugasundaram, Bharanidharan; Sase, Ajinkya; Miklosi, András G; Sialana, Fernando J; Subramaniyan, Saraswathi; Aher, Yogesh D; Gröger, Marion; Höger, Harald; Bennett, Keiryn L; Lubec, Gert

    2015-08-01

    Several neurotransmitter receptors have been proposed to be involved in memory formation. However, information on receptor complexes (RCs) in the radial arm maze (RAM) is missing. It was therefore the aim of this study to determine major neurotransmitter RCs levels that are modulated by RAM training because receptors are known to work in homo-or heteromeric assemblies. Immediate early gene Arc expression was determined by immunohistochemistry to show if prefrontal cortices (PFC) and hippocampi were activated following RAM training as these regions are known to be mainly implicated in spatial memory. Twelve rats per group, trained and untrained in the twelve arm RAM were used, frontal cortices and hippocampi were taken, RCs in membrane protein were quantified by blue-native PAGE immunoblotting. RCs components were characterised by co-immunoprecipitation followed by mass spectrometrical analysis and by the use of the proximity ligation assay. Arc expression was significantly higher in PFC of trained as compared to untrained rats whereas it was comparable in hippocampi. Frontal cortical levels of RCs containing AMPA receptors GluA1, GluA2, NMDA receptors GluN1 and GluN2A, dopamine receptor D1, acetylcholine nicotinic receptor alpha 7 (nAChR-α7) and hippocampal levels of RCs containing D1, GluN1, GluN2B and nAChR-α7 were increased in the trained group; phosphorylated dopamine transporter levels were decreased in the trained group. D1 and GluN1 receptors were shown to be in the same complex. Taken together, distinct RCs were paralleling performance in the RAM which is relevant for interpretation of previous and design of future work on RCs in memory studies. PMID:25930220

  7. From conflict management to reward-based decision making: actors and critics in primate medial frontal cortex.

    PubMed

    Silvetti, Massimo; Alexander, William; Verguts, Tom; Brown, Joshua W

    2014-10-01

    The role of the medial prefrontal cortex (mPFC) and especially the anterior cingulate cortex has been the subject of intense debate for the last decade. A number of theories have been proposed to account for its function. Broadly speaking, some emphasize cognitive control, whereas others emphasize value processing; specific theories concern reward processing, conflict detection, error monitoring, and volatility detection, among others. Here we survey and evaluate them relative to experimental results from neurophysiological, anatomical, and cognitive studies. We argue for a new conceptualization of mPFC, arising from recent computational modeling work. Based on reinforcement learning theory, these new models propose that mPFC is an Actor-Critic system. This system is aimed to predict future events including rewards, to evaluate errors in those predictions, and finally, to implement optimal skeletal-motor and visceromotor commands to obtain reward. This framework provides a comprehensive account of mPFC function, accounting for and predicting empirical results across different levels of analysis, including monkey neurophysiology, human ERP, human neuroimaging, and human behavior. PMID:24239852

  8. Acute Sleep Deprivation Induces a Local Brain Transfer Information Increase in the Frontal Cortex in a Widespread Decrease Context

    PubMed Central

    Alonso, Joan F.; Romero, Sergio; Mañanas, Miguel A.; Alcalá, Marta; Antonijoan, Rosa M.; Giménez, Sandra

    2016-01-01

    Sleep deprivation (SD) has adverse effects on mental and physical health, affecting the cognitive abilities and emotional states. Specifically, cognitive functions and alertness are known to decrease after SD. The aim of this work was to identify the directional information transfer after SD on scalp EEG signals using transfer entropy (TE). Using a robust methodology based on EEG recordings of 18 volunteers deprived from sleep for 36 h, TE and spectral analysis were performed to characterize EEG data acquired every 2 h. Correlation between connectivity measures and subjective somnolence was assessed. In general, TE showed medium- and long-range significant decreases originated at the occipital areas and directed towards different regions, which could be interpreted as the transfer of predictive information from parieto-occipital activity to the rest of the head. Simultaneously, short-range increases were obtained for the frontal areas, following a consistent and robust time course with significant maps after 20 h of sleep deprivation. Changes during sleep deprivation in brain network were measured effectively by TE, which showed increased local connectivity and diminished global integration. TE is an objective measure that could be used as a potential measure of sleep pressure and somnolence with the additional property of directed relationships. PMID:27089346

  9. We are more selfish than we think: The endowment effect and reward processing within the human medial-frontal cortex.

    PubMed

    Hassall, Cameron D; Silver, Amy; Turk, David J; Krigolson, Olave E

    2016-09-01

    Perceived ownership has been shown to impact a variety of cognitive processes: attention, memory, and-more recently-reward processing. In the present experiment we examined whether or not perceived ownership would interact with the construct of value-the relative worth of an object. Participants completed a simple gambling game in which they gambled either for themselves or for another while electroencephalographic data were recorded. In a key manipulation, gambles for oneself or for another were for either small or large rewards. We tested the hypothesis that value affects the neural response to self-gamble outcomes, but not other-gamble outcomes. Our experimental data revealed that while participants learned the correct response option for both self and other gambles, the reward positivity evoked by wins was impacted by value only when gambling for oneself. Importantly, our findings provide additional evidence for a self-ownership bias in cognitive processing and further demonstrate the insensitivity of the medial-frontal reward system to gambles for another. PMID:26490515

  10. Acute Sleep Deprivation Induces a Local Brain Transfer Information Increase in the Frontal Cortex in a Widespread Decrease Context.

    PubMed

    Alonso, Joan F; Romero, Sergio; Mañanas, Miguel A; Alcalá, Marta; Antonijoan, Rosa M; Giménez, Sandra

    2016-01-01

    Sleep deprivation (SD) has adverse effects on mental and physical health, affecting the cognitive abilities and emotional states. Specifically, cognitive functions and alertness are known to decrease after SD. The aim of this work was to identify the directional information transfer after SD on scalp EEG signals using transfer entropy (TE). Using a robust methodology based on EEG recordings of 18 volunteers deprived from sleep for 36 h, TE and spectral analysis were performed to characterize EEG data acquired every 2 h. Correlation between connectivity measures and subjective somnolence was assessed. In general, TE showed medium- and long-range significant decreases originated at the occipital areas and directed towards different regions, which could be interpreted as the transfer of predictive information from parieto-occipital activity to the rest of the head. Simultaneously, short-range increases were obtained for the frontal areas, following a consistent and robust time course with significant maps after 20 h of sleep deprivation. Changes during sleep deprivation in brain network were measured effectively by TE, which showed increased local connectivity and diminished global integration. TE is an objective measure that could be used as a potential measure of sleep pressure and somnolence with the additional property of directed relationships. PMID:27089346

  11. Intracerebroventricular administration of ouabain, a Na/K-ATPase inhibitor, activates mTOR signal pathways and protein translation in the rat frontal cortex.

    PubMed

    Kim, Se Hyun; Yu, Hyun-Sook; Park, Hong Geun; Ha, Kyooseob; Kim, Yong Sik; Shin, Soon Young; Ahn, Yong Min

    2013-08-01

    Intracerebroventricular (ICV) injection of ouabain, a specific Na/K-ATPase inhibitor, induces behavioral changes in rats in a putative animal model of mania. The binding of ouabain to Na/K-ATPase affects signaling molecules in vitro, including ERK1/2 and Akt, which promote protein translation. We have also reported that ERK1/2 and Akt in the brain are involved in the ouabain-induced hyperactivity of rats. In this study, rats were given an ICV injection of ouabain, and then their frontal cortices were examined to determine the effects of ouabain on the mTOR/p70S6K/S6 signaling pathway and protein translation, which are important in modifications of neural circuits and behavior. Rats showed ouabain-induced hyperactivity up to 8h following injection, and increased phosphorylation levels of mTOR, p70S6K, S6, eIF4B, and 4E-BP at 1, 2, 4, and 8h following ouabain injection. Immunohistochemical analyses revealed that increased p-S6 immunoreactivity in the cytoplasm of neurons by ouabain was evident in the prefrontal, cingulate, and orbital cortex. These findings suggested increased translation initiation in response to ouabain. The rate of protein synthesis was measured as the amount of [(3)H]-leucine incorporation in the cell-free extracts of frontal cortical tissues, and showed a significant increase at 8h after ouabain injection. These results suggest that ICV injection of ouabain induced activation of the protein translation initiation pathway regulated by ERK1/2 and Akt, and prolonged hyperactivity in rats. In conclusion, protein translation pathway could play an important role in ouabain-induced hyperactivity in a rodent model of mania. PMID:23643758

  12. Modulation of the release of norepinephrine by gamma-aminobutyric acid and morphine in the frontal cerebral cortex of the rat

    SciTech Connect

    Peoples, R.W.

    1989-01-01

    Agents that enhance gamma-aminobutyric acid, or GABA, neurotransmission modulate certain effects of opioids, such as analgesia. Opioid analgesia is mediated in part by norepinephrine in the forebrain. In this study, the interactions between morphine and GABAergic agents on release of ({sup 3}H) norepinephrine from rat frontal cerebral cortical slices were examined. GABA, 5 {times} 10{sup {minus}5}-10{sup {minus}3} M, enhanced potassium stimulated ({sup 3}H) norepinephrine release and reversed the inhibitory effect of morphine in a noncompetitive manner. GABA did not enhance release of ({sup 3}H) norepinephrine stimulated by the calcium ionophore A23187. The effect of GABA was reduced by the GABA{sub A} receptor antagonists bicuculline methiodide or picrotoxin, and by the selective inhibitor of GABA uptake SKF 89976A, but was blocked completely only when bicuculline methiodide and SKF 89976A were used in combination. The GABA{sub A} agonist muscimol, 10{sup {minus}4} M, mimicked the effect of GABA, but the GABA{sub B} agonist ({plus minus})baclofen, 10{sup {minus}4} M, did not affect the release of ({sup 3}H) norepinephrine in the absence or the presence of morphine. Thus GABA appears to produce this effect by stimulating GABA uptake and GABA{sub A}, but not GABA{sub B}, receptors. In contrast to the results that would be predicted for an event involving GABA{sub A} receptors, however, the effect of GABA did not desensitize, and benzodiazepine agonists did not enhance the effect of GABA at any concentration tested between 10{sup {minus}8} and 10{sup {minus}4} M. Thus these receptors may constitute a subclass of GABA{sub A} receptors. These results support a role of GABA uptake and GABA{sub A} receptors in enhancing the release of norepinephrine and modulating its inhibition by opioids in the frontal cortex of the rat.

  13. Aerobic Glycolysis in the Frontal Cortex Correlates with Memory Performance in Wild-Type Mice But Not the APP/PS1 Mouse Model of Cerebral Amyloidosis

    PubMed Central

    Harris, Richard A.; Tindale, Lauren; Lone, Asad; Singh, Olivia; Macauley, Shannon L.; Stanley, Molly; Holtzman, David M.; Bartha, Robert

    2016-01-01

    Aerobic glycolysis and lactate production in the brain plays a key role in memory, yet the role of this metabolism in the cognitive decline associated with Alzheimer's disease (AD) remains poorly understood. Here we examined the relationship between cerebral lactate levels and memory performance in an APP/PS1 mouse model of AD, which progressively accumulates amyloid-β. In vivo 1H-magnetic resonance spectroscopy revealed an age-dependent decline in lactate levels within the frontal cortex of control mice, whereas lactate levels remained unaltered in APP/PS1 mice from 3 to 12 months of age. Analysis of hippocampal interstitial fluid by in vivo microdialysis revealed a significant elevation in lactate levels in APP/PS1 mice relative to control mice at 12 months of age. An age-dependent decline in the levels of key aerobic glycolysis enzymes and a concomitant increase in lactate transporter expression was detected in control mice. Increased expression of lactate-producing enzymes correlated with improved memory in control mice. Interestingly, in APP/PS1 mice the opposite effect was detected. In these mice, increased expression of lactate producing enzymes correlated with poorer memory performance. Immunofluorescent staining revealed localization of the aerobic glycolysis enzymes pyruvate dehydrogenase kinase and lactate dehydrogenase A within cortical and hippocampal neurons in control mice, as well as within astrocytes surrounding amyloid plaques in APP/PS1 mice. These observations collectively indicate that production of lactate, via aerobic glycolysis, is beneficial for memory function during normal aging. However, elevated lactate levels in APP/PS1 mice indicate perturbed lactate processing, a factor that may contribute to cognitive decline in AD. SIGNIFICANCE STATEMENT Lactate has recently emerged as a key metabolite necessary for memory consolidation. Lactate is the end product of aerobic glycolysis, a unique form of metabolism that occurs within certain

  14. Same Modulation but Different Starting Points: Performance Modulates Age Differences in Inferior Frontal Cortex Activity during Word-Retrieval

    PubMed Central

    Meinzer, Marcus; Flaisch, Tobias; Seeds, Lauren; Harnish, Stacy; Antonenko, Daria; Witte, Veronica; Lindenberg, Robert; Crosson, Bruce

    2012-01-01

    The neural basis of word-retrieval deficits in normal aging has rarely been assessed and the few previous functional imaging studies found enhanced activity in right prefrontal areas in healthy older compared to younger adults. However, more pronounced right prefrontal recruitment has primarily been observed during challenging task conditions. Moreover, increased task difficulty may result in enhanced activity in the ventral inferior frontal gyrus (vIFG) bilaterally in younger participants as well. Thus, the question arises whether increased activity in older participants represents an age-related phenomenon or reflects task difficulty effects. In the present study, we manipulated task difficulty during overt semantic and phonemic word-generation and used functional magnetic resonance imaging to assess activity patterns in the vIFG in healthy younger and older adults (N = 16/group; mean age: 24 vs. 69 years). Both groups produced fewer correct responses during the more difficult task conditions. Overall, older participants produced fewer correct responses and showed more pronounced task-related activity in the right vIFG. However, increased activity during the more difficult conditions was found in both groups. Absolute degree of activity was correlated with performance across groups, tasks and difficulty levels. Activity modulation (difficult vs. easy conditions) was correlated with the respective drop in performance across groups and tasks. In conclusion, vIFG activity levels and modulation of activity were mediated by performance accuracy in a similar way in both groups. Group differences in the right vIFG activity were explained by performance accuracy which needs to be considered in future functional imaging studies of healthy and pathological aging. PMID:22438970

  15. Same modulation but different starting points: performance modulates age differences in inferior frontal cortex activity during word-retrieval.

    PubMed

    Meinzer, Marcus; Flaisch, Tobias; Seeds, Lauren; Harnish, Stacy; Antonenko, Daria; Witte, Veronica; Lindenberg, Robert; Crosson, Bruce

    2012-01-01

    The neural basis of word-retrieval deficits in normal aging has rarely been assessed and the few previous functional imaging studies found enhanced activity in right prefrontal areas in healthy older compared to younger adults. However, more pronounced right prefrontal recruitment has primarily been observed during challenging task conditions. Moreover, increased task difficulty may result in enhanced activity in the ventral inferior frontal gyrus (vIFG) bilaterally in younger participants as well. Thus, the question arises whether increased activity in older participants represents an age-related phenomenon or reflects task difficulty effects. In the present study, we manipulated task difficulty during overt semantic and phonemic word-generation and used functional magnetic resonance imaging to assess activity patterns in the vIFG in healthy younger and older adults (N = 16/group; mean age: 24 vs. 69 years). Both groups produced fewer correct responses during the more difficult task conditions. Overall, older participants produced fewer correct responses and showed more pronounced task-related activity in the right vIFG. However, increased activity during the more difficult conditions was found in both groups. Absolute degree of activity was correlated with performance across groups, tasks and difficulty levels. Activity modulation (difficult vs. easy conditions) was correlated with the respective drop in performance across groups and tasks. In conclusion, vIFG activity levels and modulation of activity were mediated by performance accuracy in a similar way in both groups. Group differences in the right vIFG activity were explained by performance accuracy which needs to be considered in future functional imaging studies of healthy and pathological aging. PMID:22438970

  16. The Role of the Lateral Frontal Cortex in Causal Associative Learning: Exploring Preventative and Super-learning

    PubMed Central

    Turner, Danielle C.; Aitken, Michael R.F.; Shanks, David R.; Sahakian, Barbara J.; Robbins, Trevor W.; Schwarzbauer, Christian; Fletcher, Paul C.

    2012-01-01

    Prediction error — a mismatch between expected and actual outcome — is critical to associative accounts of inferential learning. However, it has proven difficult to explore the effects of prediction error using functional magnetic resonance imaging (fMRI) while excluding the confounding effects of stimulus novelty and incorrect responses. In this event-related fMRI study we used a three-stage experiment generating preventative- and super-learning conditions. In both cases, it was possible to generate prediction error within a causal associative learning experiment while subtracting the effects of novelty and error. We show that right lateral prefrontal cortex (PFC) activation is sensitive to the magnitude of prediction error. Furthermore, super-learning activation in this region of PFC correlates, across subjects, with the amount learned. We thus provide direct evidence for a brain correlate of the surprise-dependent mechanisms proposed by associative accounts of causal learning. We show that activity in right lateral PFC is sensitive to the magnitude, though not the direction, of the prediction error. Furthermore, its activity is not directly explicable in terms of novelty or response errors and appears directly related to the learning that arises out of prediction error. PMID:15054060

  17. The role of the lateral frontal cortex in causal associative learning: exploring preventative and super-learning.

    PubMed

    Turner, Danielle C; Aitken, Michael R F; Shanks, David R; Sahakian, Barbara J; Robbins, Trevor W; Schwarzbauer, Christian; Fletcher, Paul C

    2004-08-01

    Prediction error--a mismatch between expected and actual outcome--is critical to associative accounts of inferential learning. However, it has proven difficult to explore the effects of prediction error using functional magnetic resonance imaging (fMRI) while excluding the confounding effects of stimulus novelty and incorrect responses. In this event-related fMRI study we used a three-stage experiment generating preventative- and super-learning conditions. In both cases, it was possible to generate prediction error within a causal associative learning experiment while subtracting the effects of novelty and error. We show that right lateral prefrontal cortex (PFC) activation is sensitive to the magnitude of prediction error. Furthermore, super-learning activation in this region of PFC correlates, across subjects, with the amount learned. We thus provide direct evidence for a brain correlate of the surprise-dependent mechanisms proposed by associative accounts of causal learning. We show that activity in right lateral PFC is sensitive to the magnitude, though not the direction, of the prediction error. Furthermore, its activity is not directly explicable in terms of novelty or response errors and appears directly related to the learning that arises out of prediction error. PMID:15054060

  18. Sex-dependent effects of lead and prenatal stress on post-translational histone modifications in frontal cortex and hippocampus in the early postnatal brain.

    PubMed

    Schneider, Jay S; Anderson, David W; Kidd, Sarah K; Sobolewski, Marissa; Cory-Slechta, Deborah A

    2016-05-01

    Environmental lead (Pb) exposure and prenatal stress (PS) are co-occurring risk factors for impaired cognition and other disorders/diseases in adulthood and target common biological substrates in the brain. Sex-dependent differences characterize the neurochemical and behavioral responses of the brain to Pb and PS and sexually dimorphic histone modifications have been reported to occur in at-risk brain regions (cortex and hippocampus) during development. The present study sought to examine levels and developmental timing of sexually dimorphic histone modifications (i.e., H3K9/14Ac and H3K9Me3) and the extent to which they may be altered by Pb±PS. Female C57/Bl6 mice were randomly assigned to receive distilled deionized drinking water containing 0 or 100ppm Pb acetate for 2 months prior to breeding and throughout lactation. Half of the dams in each group were exposed to restraint stress (PS, three restraint sessions in plastic cylindrical devices 3×/day at for 30min/day (1000, 1300, and 1600h)) from gestational day 11-19 or no stress (NS). At delivery (PND0) and postnatal day 6 (PND6), pups were euthanized and frontal cortex and hippocampus were removed, homogenized, and assayed for levels of H3K9/14Ac and H3K9Me3. Sex-dependent differences in both levels of histone modifications as well as the developmental trajectory of changes in these levels were observed in both structures and these parameters were differentially affected by Pb±PS in a sex and brain-region-dependent manner. Disruptions of these epigenetic processes by developmental Pb±PS may underlie some of the sex-dependent neurobehavioral differences previously observed in these animals. PMID:27018513

  19. Increases in mature brain-derived neurotrophic factor protein in the frontal cortex and basal forebrain during chronic sleep restriction in rats: possible role in initiating allostatic adaptation.

    PubMed

    Wallingford, J K; Deurveilher, S; Currie, R W; Fawcett, J P; Semba, K

    2014-09-26

    Chronic sleep restriction (CSR) has various negative consequences on cognitive performance and health. Using a rat model of CSR that uses alternating cycles of 3h of sleep deprivation (using slowly rotating activity wheels) and 1h of sleep opportunity continuously for 4 days ('3/1' protocol), we previously observed not only homeostatic but also allostatic (adaptive) sleep responses to CSR. In particular, non-rapid eye movement sleep (NREMS) electroencephalogram (EEG) delta power, an index of sleep intensity, increased initially and then declined gradually during CSR, with no rebound during a 2-day recovery period. To study underlying mechanisms of these allostatic responses, we examined the levels of brain-derived neurotrophic factor (BDNF), which is known to regulate NREMS EEG delta activity, during the same CSR protocol. Mature BDNF protein levels were measured in the frontal cortex and basal forebrain, two brain regions involved in sleep and EEG regulation, and the hippocampus, using Western blot analysis. Adult male Wistar rats were housed in motorized activity wheels, and underwent the 3/1 CSR protocol for 27 h, for 99 h, or for 99 h followed by 24h of recovery. Additional rats were housed in either locked wheels (locked wheel controls [LWCs]) or unlocked wheels that rats could rotate freely (wheel-running controls [WRCs]). BDNF levels did not differ between WRC and LWC groups. BDNF levels were increased, compared to the control levels, in all three brain regions after 27 h, and were increased less strongly after 99 h, of CSR. After 24h of recovery, BDNF levels were at the control levels. This time course of BDNF levels parallels the previously reported changes in NREMS delta power during the same CSR protocol. Changes in BDNF protein levels in the cortex and basal forebrain may be part of the molecular mechanisms underlying allostatic sleep responses to CSR. PMID:25010399

  20. Human subthalamic nucleus-medial frontal cortex theta phase coherence is involved in conflict and error related cortical monitoring.

    PubMed

    Zavala, Baltazar; Tan, Huiling; Ashkan, Keyoumars; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Zaghloul, Kareem; Brown, Peter

    2016-08-15

    The medial prefrontal cortex (mPFC) is thought to control the shift from automatic to controlled action selection when conflict is present or when mistakes have been recently committed. Growing evidence suggests that this process involves frequency specific communication in the theta (4-8Hz) band between the mPFC and the subthalamic nucleus (STN), which is the main target of deep brain stimulation (DBS) for Parkinson's disease. Key in this hypothesis is the finding that DBS can lead to impulsivity by disrupting the correlation between higher mPFC oscillations and slower reaction times during conflict. In order to test whether theta band coherence between the mPFC and the STN underlies adjustments to conflict and to errors, we simultaneously recorded mPFC and STN electrophysiological activity while DBS patients performed an arrowed flanker task. These recordings revealed higher theta phase coherence between the two sites during the high conflict trials relative to the low conflict trials. These differences were observed soon after conflicting arrows were displayed, but before a response was executed. Furthermore, trials that occurred after an error was committed showed higher phase coherence relative to trials that followed a correct trial, suggesting that mPFC-STN connectivity may also play a role in error related adjustments in behavior. Interestingly, the phase coherence we observed occurred before increases in theta power, implying that the theta phase and power may influence behavior at separate times during cortical monitoring. Finally, we showed that pre-stimulus differences in STN theta power were related to the reaction time on a given trial, which may help adjust behavior based on the probability of observing conflict during a task. PMID:27181763

  1. Effects of Hypertension and Anti-Hypertensive Treatment on Amyloid-β (Aβ) Plaque Load and Aβ-Synthesizing and Aβ-Degrading Enzymes in Frontal Cortex.

    PubMed

    Ashby, Emma L; Miners, James S; Kehoe, Patrick G; Love, Seth

    2016-01-01

    Epidemiological data associate hypertension with a predisposition to Alzheimer's disease (AD), and a number of postmortem and in vivo studies also demonstrate that hypertension increases amyloid-β (Aβ) pathology. In contrast, anti-hypertensive medications reportedly improve cognition and decrease the risk of AD, while certain classes of anti-hypertensive drugs are associated with decreased AD-related pathology. We investigated the effects of hypertension and anti-hypertensive treatment on Aβ plaque load in postmortem frontal cortex in AD. Aβ load was significantly increased in hypertensive (n = 20) relative to normotensive cases (n = 62) and was also significantly higher in treated (n = 9) than untreated hypertensives (n = 11). We then looked into mechanisms by which hypertension and treatment might increase Aβ load, focusing on Aβ-synthesizing enzymes, β- and γ-secretase, and Aβ-degrading enzymes, angiotensin-converting enzyme (ACE), insulin-degrading enzyme (IDE) and neprilysin. ACE and IDE protein levels were significantly lower in hypertensive (n = 21) than normotensive cases (n = 64), perhaps translating to decreased Aβ catabolism in hypertensives. ACE level was significantly higher in treated (n = 9) than untreated hypertensives (n = 12), possibly reflecting feedback upregulation of the renin-angiotensin system. Prospective studies in larger cohorts stratified according to anti-hypertensive drug class are needed to confirm these initial findings and to elucidate the interactions between hypertension, anti-hypertensive treatments, and Aβ metabolism. PMID:26836178

  2. Endurance training effects on 5-HT(1B) receptors mRNA expression in cerebellum, striatum, frontal cortex and hippocampus of rats.

    PubMed

    Chennaoui, M; Drogou, C; Gomez-Merino, D; Grimaldi, B; Fillion, G; Guezennec, C Y

    2001-07-01

    The 5-HT(1B) receptors are the predominant auto- and heteroreceptors located on serotonergic and non-serotonergic terminals where they regulate the neuronal release of neurotransmitters. The present study investigated the effects of a 7 week period of physical training on the expression of cerebral 5-HT(1B) receptors by measuring corresponding mRNA levels in rat. Using RNase protection assay technique, we have observed no change in 5-HT(1B) receptor mRNA levels in the striatum and in the hippocampus after moderate as well as after intensive training. In contrast, a significant decrease in 5-HT(1B) receptor mRNA levels was observed in cerebellum of intensively trained rats. Moreover, in frontal cortex, a significant decrease in 5-HT(1B) receptors mRNA level occurred in both groups of trained rats. These data suggest the existence of regional differences in the effect of physical exercise on the expression of 5-HT(1B) receptors. PMID:11516568

  3. Maternal separation and early stress cause long-lasting effects on dopaminergic and endocannabinergic systems and alters dendritic morphology in the nucleus accumbens and frontal cortex in rats.

    PubMed

    Romano-López, Antonio; Méndez-Díaz, Mónica; García, Fabio García; Regalado-Santiago, Citlalli; Ruiz-Contreras, Alejandra E; Prospéro-García, Oscar

    2016-08-01

    A considerable amount experimental studies have shown that maternal separation (MS) is associated with adult offspring abnormal behavior and cognition disorder. Accordingly, this experimental procedure has been proposed as a predictor for alcohol and drug dependence based on the neurodevelopmental soon after birth. Endocannabinoid system (eCBs) has been implicated in reward processes, including drug abuse and dependence. MS and associated stress causes changes in the eCBs that seem to facilitate alcohol consumption. In this study, we seek to evaluate potential morphological changes in neurons of the frontal cortex (FCx) and nucleus accumbens (NAcc), in the expression of receptors and enzymes of the endocannabinoid and dopamine systems and in second messengers, such as Akt, in adult rats subjected to MS and early stress (MS + ES; 2 × 180 min daily) vs. nonseparated rats (NMS). Results showed that MS + ES induces higher D2R expression and lower D3R, FAAH, and MAGL expression compared with NMS rats. Alterations in total dendritic length were also detected and were characterized by increases in the NAcc while there were decreases in the FCx. We believe MS + ES-induced changes in the dopaminergic and endocannabinergic systems and in the neuronal microstructure might be contributing to alcohol seeking behavior and, potential vulnerability to other drugs in rats. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 819-831, 2016. PMID:26539755

  4. Reduced C9orf72 protein levels in frontal cortex of amyotrophic lateral sclerosis and frontotemporal degeneration brain with the C9ORF72 hexanucleotide repeat expansion☆

    PubMed Central

    Waite, Adrian J.; Bäumer, Dirk; East, Simon; Neal, James; Morris, Huw R.; Ansorge, Olaf; Blake, Derek J.

    2014-01-01

    An intronic G4C2 hexanucleotide repeat expansion in C9ORF72 is a major cause of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Several mechanisms including RNA toxicity, repeat-associated non-AUG translation mediated dipeptide protein aggregates, and haploinsufficiency of C9orf72 have been implicated in the molecular pathogenesis of this disorder. The aims of this study were to compare the use of two different Southern blot probes for detection of repeat expansions in an amyotrophic lateral sclerosis and frontotemporal lobar degeneration pathological cohort and to determine the levels of C9orf72 transcript variants and protein isoforms in patients versus control subjects. Our Southern blot studies identified smaller repeat expansions (250–1800 bp) that were only detectable with the flanking probe highlighting the potential for divergent results using different Southern blotting protocols that could complicate genotype–phenotype correlation studies. Further, we characterize a new C9orf72 antibody and show for the first time decreased C9orf72 protein levels in the frontal cortex from patients with a pathological hexanucleotide repeat expansion. These data suggest that a reduction in C9orf72 protein may be a consequence of the disease. PMID:24559645

  5. Higher levels of phosphorylated Y1472 on GluN2B subunits in the frontal cortex of aged mice are associated with good spatial reference memory, but not cognitive flexibility.

    PubMed

    Zamzow, Daniel R; Elias, Val; Acosta, Varinia A; Escobedo, Emily; Magnusson, Kathy R

    2016-06-01

    The N-methyl-D-aspartate receptor (NMDAr) is particularly vulnerable to aging. The GluN2B subunit of the NMDAr, compared to other NMDAr subunits, suffers the greatest losses of expression in the aging brain, especially in the frontal cortex. While expression levels of GluN2B mRNA and protein in the aged brain are well documented, there has been little investigation into age-related posttranslational modifications of the subunit. In this study, we explored some of the mechanisms that may promote differences in the NMDAr complex in the frontal cortex of aged animals. Two ages of mice, 3 and 24 months, were behaviorally tested in the Morris water maze. The frontal cortex and hippocampus from each mouse were subjected to differential centrifugation followed by solubilization in Triton X-100. Proteins from Triton-insoluble membranes, Triton-soluble membranes, and intracellular membranes/cytosol were examined by Western blot. Higher levels of GluN2B tyrosine 1472 phosphorylation in frontal cortex synaptic fractions of old mice were associated with better reference learning but poorer cognitive flexibility. Levels of GluN2B phosphotyrosine 1336 remained steady, but there were greater levels of the calpain-induced 115 kDa GluN2B cleavage product on extrasynaptic membranes in these old good learners. There was an age-related increase in calpain activity, but it was not associated with better learning. These data highlight a unique aging change for aged mice with good spatial learning that might be detrimental to cognitive flexibility. This study also suggests that higher levels of truncated GluN2B on extrasynaptic membranes are not deleterious to spatial memory in aged mice. PMID:27094400

  6. Amphetamine Up-Regulates AGS1 mRNA and Protein Levels in Rat Frontal Cortex: The Role of Dopamine and Glucocorticoid Receptors

    PubMed Central

    Schwendt, Marek; McGinty, Jacqueline F.

    2010-01-01

    Acute and chronic exposure to psychostimulants results in altered function of G-protein-coupled receptors in the forebrain. It is believed that neuroadaptations in G-protein signaling contribute to behavioral sensitivity to psychostimulants that persists over a prolonged drug-free period. Proteins termed activators of G-protein signaling (AGS) have been characterized as potent modulators of both receptor-dependent and receptor-independent G-protein signaling. Nevertheless, the regulation of AGS gene and protein expression by psychostimulants remains poorly understood. In the present study, we investigated amphetamine (AMPH)-induced changes in expression patterns of several forebrain-enriched AGS proteins. A single exposure to AMPH (2.5 mg/kg i.p.) selectively induced gene expression of AGS1, but not Rhes or AGS3 proteins, in the rat prefrontal cortex (PFC) as measured 3h later. Induction of AGS1 mRNA in the PFC by acute AMPH was transient and dose-dependent. Even repeated treatment with AMPH for 5 days did not produce lasting changes in AGS1 mRNA and protein levels in the PFC as measured three weeks post treatment. However, at this time point, a low dose AMPH challenge (1 mg/kg, i.p.) induced a robust behavioral response and up-regulated AGS1 expression in the PFC selectively in animals with an AMPH history. The effects of AMPH on AGS1 expression in the PFC were blocked by a D2, but not D1, dopamine receptor antagonist and partially by a glucocorticoid receptor antagonist. Collectively, the present study suggests that (1) AGS1 represents a regulator of G-protein signaling that is rapidly inducible by AMPH in the frontal cortex, (2) AGS1 regulation in the PFC parallels behavioral activation by acute AMPH in drug-naïve animals and hypersensitivity to AMPH challenge in sensitized animals, and (3) D2 dopamine and glucocorticoid receptors regulate AMPH effects on AGS1 in the PFC. Changes in AGS1 levels in the PFC may result in abnormal receptor-to-G-protein coupling

  7. Gamma-hydroxybutyrate reduces mitogen-activated protein kinase phosphorylation via GABA B receptor activation in mouse frontal cortex and hippocampus.

    PubMed

    Ren, Xiuhai; Mody, Istvan

    2003-10-24

    gamma-Hydroxybutyrate (GHB) naturally occurs in the brain, but its exogenous administration induces profound effects on the central nervous system in animals and humans. The intracellular signaling mechanisms underlying its actions remain unclear. In the present study, the effects of GHB on the activation (phosphorylation) of mitogen-activated protein kinases (MAP kinases), extracellular signal-regulated kinase 1 and 2 (ERK1/2), were investigated. Acute administration of GHB (500 mg/kg, intraperitoneal) induced a fast and long lasting inhibition of MAP kinase phosphorylation in both frontal cortex and hippocampus. The reduced MAP kinase phosphorylation was observed in the CA1 and CA3 areas but not in the dentate gyrus. Pretreatment with the specific gamma-aminobutyric acid, type B (GABAB), receptor antagonist CGP56999A (20 mg/kg, intraperitoneal) prevented the action of GHB, and the effect of GHB was mimicked by baclofen, a selective GABAB receptor agonist, whereas the high affinity GHB receptor antagonist NCS-382 (200 mg/kg, intraperitoneal) had no effect on GHB-inhibited MAP kinase phosphorylation. Moreover, the GHB dehydrogenase inhibitor valproate (500 mg/kg, intraperitoneal), which inhibits the conversion of GHB into GABA, failed to block the effect of GHB on MAP kinase phosphorylation. Altogether, these data suggest that GHB, administered in vivo, reduces MAP kinase phosphorylation via a direct activation of GABAB receptors by GHB. In contrast, GHB (10 mm for 15 min) was found ineffective on MAP kinase phosphorylation in brain slices, indicating important differences in the conditions required for the second messenger activating action of GHB. PMID:12923192

  8. Efferents from the lateral frontal cortex to spinomedullary target areas, trigeminal nuclei, and spinally projecting brainstem regions in the hedgehog tenrec.

    PubMed

    Künzle, H; Lotter, G

    1996-08-12

    This study was done in the Madagascan lesser hedgehog tenrec, an insectivore with a very poorly differentiated neocortex. The cortical region, known to give rise to spinal projections, was injected with tracer, and the cortical efferents to brainstem and spinal cord were analyzed. Bulbar reticular fields, in addition, were identified according to their cells of origin and the laterality of their spinal projections after injection of tracer. Only few cortical fibers could be traced from the bulbar pyramid into the ipsilateral spinal cord, particularly to the lateral funiculus. The projections to the dorsal column nuclei and the classical spinally projecting brainstem regions were also weak. Faint projections were demonstrated to the nucleus of the posterior commissure and the nucleus of Darkschewitsch. In comparison to other mammals, there was no evidence that the contralateral cortico-bulbo-spinal pathway was strengthened, substituting for the almost non-existent contralateral corticospinal projection. Unlike the sensorimotor apparatus controlling limb and body movements, the brainstem regions controlling the head and neck received prominent cortical projections. Direct corticotrigeminal projections and indirect pathways were well represented. The projections to the trigeminal nuclei and the lateral reticular fields were clearly bilateral; those to the superior colliculus were predominantly ipsilateral. The corticobulbar fibers left the pyramid along its entire extent; the principal trigeminal nucleus and the dorsolateral pontine tegmentum were supplied by additional fibers of the corticotegmental tract. The lateral frontal cortex also projected densely to the dorsolateral hypothalamus, the periaqueductal gray, and the adjacent mesencephalic tegmentum, components of the emotional motor system. PMID:8841923

  9. A Biphasic Change of Regional Blood Volume in the Frontal Cortex during Non-Rapid Eye Movement Sleep: A Near-Infrared Spectroscopy Study

    PubMed Central

    Zhang, Zhongxing; Khatami, Ramin

    2015-01-01

    Study Objectives: Current knowledge on hemodynamics in sleep is limited because available techniques do not allow continuous recordings and mainly focus on cerebral blood flow while neglecting other important parameters, such as blood volume (BV) and vasomotor activity. Design: Observational study. Participants and Settings: Continuous measures of hemodynamics over the left forehead and biceps were performed using near-infrared spectroscopy (NIRS) during nocturnal polysomnography in 16 healthy participants in sleep laboratory. Measurements and Results: Temporal dynamics and mean values of cerebral and muscular oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (HHb), and BV during different sleep stages were compared. A biphasic change of cerebral BV was observed which contrasted a monotonic increase of muscular BV during non-rapid eye movement sleep. A significant decrement in cerebral HbO2 and BV accompanied by an increase of HHb was recorded at sleep onset (Phase I). Prior to slow wave sleep (SWS) HbO2 and BV turned to increase whereas HHb began to decrease in subsequent Phase II suggested increased brain perfusion during SWS. The cerebral HbO2 slope correlated to BV slope in Phase I and II, but it only correlated to HHb slope in Phase II. The occurrence time of inflection points correlated to SWS latencies. Conclusion: Initial decrease of brain perfusion with decreased blood volume (BV) and oxygenated hemoglobin (HbO2) together with increasing muscular BV fit thermoregulation process at sleep onset. The uncorrelated and correlated slopes of HbO2 and deoxygenated hemoglobin indicate different mechanisms underlying the biphasic hemodynamic process in light sleep and slow wave sleep (SWS). In SWS, changes in vasomotor activity (i.e., increased vasodilatation) may mediate increasing cerebral and muscular BV. Citation: Zhang Z, Khatami R. A biphasic change of regional blood volume in the frontal cortex during non-rapid eye movement sleep: a near

  10. Genome-Wide DNA Methylation Differences Between Late-Onset Alzheimer’s Disease and Cognitively Normal Controls in Human Frontal Cortex

    PubMed Central

    Bakulski, Kelly M.; Dolinoy, Dana C.; Sartor, Maureen A.; Paulson, Henry L.; Konen, John R.; Lieberman, Andrew P.; Albin, Roger L.; Hu, Howard; Rozek, Laura S.

    2013-01-01

    Evidence supports a role for epigenetic mechanisms in the pathogenesis of late-onset Alzheimer’s disease (LOAD), but little has been done on a genome-wide scale to identify potential sites involved in disease. This study investigates human postmortem frontal cortex genome-wide DNA methylation profiles between 12 LOAD and 12 cognitively normal age- and gender-matched subjects. Quantitative DNA methylation is determined at 27,578 CpG sites spanning 14,475 genes via the Illumina Infinium HumanMethylation27 BeadArray. Data are analyzed using parallel linear models adjusting for age and gender with empirical Bayes standard error methods. Gene-specific technical and functional validation is performed on an additional 13 matched pair samples, encompassing a wider age range. Analysis reveals 948 CpG sites representing 918 unique genes as potentially associated with LOAD disease status pending confirmation in additional study populations. Across these 948 sites the subtle mean methylation difference between cases and controls is 2.9%. The CpG site with a minimum false discovery rate located in the promoter of the gene Transmembrane Protein 59 (TMEM59) is 7.3% hypomethylated in cases. Methylation at this site is functionally associated with tissue RNA and protein levels of the TMEM59 gene product. The TMEM59 gene identified from our discovery approach was recently implicated in amyloid-β protein precursor post-translational processing, supporting a role for epigenetic change in LOAD pathology. This study demonstrates widespread, modest discordant DNA methylation in LOAD-diseased tissue independent from DNA methylation changes with age. Identification of epigenetic biomarkers of LOAD risk may allow for the development of novel diagnostic and therapeutic targets. PMID:22451312

  11. Sex differences in myelin-associated protein levels within and density of projections between the orbital frontal cortex and dorsal striatum of adult rats: implications for inhibitory control.

    PubMed

    Bayless, D W; Daniel, J M

    2015-08-01

    Impulsive actions and decisions often lead to undesirable outcomes. Lesion and neuroimaging studies have revealed that the orbital frontal cortex (OFC) and dorsal striatum (dSTR) play key roles in inhibitory control. It has been proposed that greater OFC input into the dSTR reflects enhanced top-down cognitive control and less impulsive responding. We previously reported a sex difference in inhibitory control, such that female rats make fewer impulsive errors than do male rats. The goal of the present study was to investigate differences in the OFC and dSTR of young adult male and female rats. In Experiment 1, we measured levels of two myelin-associated proteins, myelin basic protein (MBP) and myelin proteolipid protein (PLP), in the OFC and dSTR. Western blot data revealed that females had significantly higher levels of both MBP and PLP in the OFC but similar levels in the dSTR as compared to males. In Experiment 2, we infused the anterograde tracer, biotinylated dextran amine (BDA), into the OFC and measured the density of BDA in the dSTR. BDA was visualized using histochemistry followed by light microscopy imaging and densitometry analysis. Density of BDA in the dSTR was significantly greater in females as compared to males indicating that the projections from the OFC to dSTR may be greater in females as compared to males. Our results suggest a potential neuroanatomical sex difference that may contribute to the reported differences in inhibitory control levels of male and female rats. PMID:26002313

  12. Oral administration of curcumin relieves behavioral alterations and oxidative stress in the frontal cortex, hippocampus, and striatum of ovariectomized Wistar rats.

    PubMed

    Da Silva Morrone, Maurilio; Schnorr, Carlos Eduardo; Behr, Guilherme Antônio; Gasparotto, Juciano; Bortolin, Rafael Calixto; Moresco, Karla Suzana; Bittencourt, Leonardo; Zanotto-Filho, Alfeu; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca

    2016-06-01

    Menopause occurs gradually and is characterized by increased susceptibility to developing mood disorders. Several studies have suggested treatments based on the antioxidant properties of vitamins and herbal compounds as an alternative to hormone replacement therapies, with few or none reporting toxicity. The present study was performed to explore the effects of curcumin oral supplementation on anxiety-like behavior and oxidative stress parameters in different central nervous system (CNS) areas of ovariectomized (OVX) rats. Female Wistar rats were randomly divided into either sham-operated or OVX groups. Sham-operated group (n=8) and an OVX group (n=11) were treated with vehicle, and the other two OVX groups received curcumin at 50 or 100mg/kg/day doses (n=8/group). Elevated plus maze (EPM) test was performed on the 28th day of treatment. On the 30th day, animals were killed and the dissected brain regions were removed and stored at-80°C until analysis. Ovariectomy induced deficit in the locomotor activity and increased anxiety-like behavior. Moreover, OVX rats showed increased lipid oxidized in the frontal cortex and striatum, increased hippocampal and striatal carbonylated protein level, and decreased striatal thiol content of non-protein fraction indicative of a glutathione (GSH) pool. Curcumin oral treatment for 30days reduced oxidative stress in the CNS areas as well as the behavior alterations resulting from ovariectomy. Curcumin supplementation attenuated most of these parameters to sham comparable values, suggesting that curcumin could have positive effects against anxiety-like disturbances and brain oxidative damage due to hormone deprivation. PMID:27142750

  13. Vulnerability versus resilience to prenatal stress in male and female rats; implications from gene expression profiles in the hippocampus and frontal cortex.

    PubMed

    Van den Hove, D L A; Kenis, G; Brass, A; Opstelten, R; Rutten, B P F; Bruschettini, M; Blanco, C E; Lesch, K P; Steinbusch, H W M; Prickaerts, J

    2013-10-01

    Adverse life events during pregnancy may impact upon the developing fetus, predisposing prenatally stressed offspring to the development of psychopathology. In the present study, we examined the effects of prenatal restraint stress (PS) on anxiety- and depression-related behavior in both male and female adult Sprague-Dawley rats. In addition, gene expression profiles within the hippocampus and frontal cortex (FC) were examined in order to gain more insight into the molecular mechanisms that mediate the behavioral effects of PS exposure. PS significantly increased anxiety-related behavior in male, but not female offspring. Likewise, depression-related behavior was increased in male PS rats only. Further, male PS offspring showed increased basal plasma corticosterone levels in adulthood, whereas both PS males and females had lower stress-induced corticosterone levels when compared to controls. Microarray-based profiling of the hippocampus and FC showed distinct sex-dependent changes in gene expression after PS. Biological processes and/or signal transduction cascades affected by PS included glutamatergic and GABAergic neurotransmission, mitogen-activated protein kinase (MAPK) signaling, neurotrophic factor signaling, phosphodiesterase (PDE)/ cyclic nucleotide signaling, glycogen synthase kinase 3 (GSK3) signaling, and insulin signaling. Further, the data indicated that epigenetic regulation is affected differentially in male and female PS offspring. These sex-specific alterations may, at least in part, explain the behavioral differences observed between both sexes, i.e. relative vulnerability versus resilience to PS in male versus female rats, respectively. These data reveal novel potential targets for antidepressant and mood stabilizing drug treatments including PDE inhibitors and histone deacetylase (HDAC) inhibitors. PMID:23199416

  14. Relationship between somatostatin and death receptor expression in the orbital frontal cortex in schizophrenia: a postmortem brain mRNA study

    PubMed Central

    Joshi, Dipesh; Catts, Vibeke S; Olaya, Juan C; Shannon Weickert, Cynthia

    2015-01-01

    Background: Recently, we provided evidence showing reductions in GAD67 and Dlx mRNAs in the orbital frontal cortex (OFC) in schizophrenia. It is unknown whether these reductions relate mainly to somatostatin (SST) or parvalbumin (PV) mRNA expression changes, and/or whether these reductions are related to decreased SST mRNA+ interneuron density. Aims: To determine whether inhibitory interneuron deficits in the OFC from people with schizophrenia are greatest for SST or PV mRNAs, and whether any such deficits relate to mRNAs encoding cell death signalling molecules. Methods: Inhibitory interneuron mRNAs (SST; PV: in situ hybridization, quantitative PCR (qPCR)) and death signaling mRNAs [FAS receptor (FASR); TNFSF13: qPCR] were measured in control and schizophrenia subjects (38/38). SST mRNA+ interneuron-like cells were quantified in layer II in the gyrus rectus. Gray matter SST and PV mRNAs were correlated with interstitial white matter neuron (IWMN) density (GAD65/67; NeuN) and death signaling mRNAs. Results: SST mRNA was reduced in OFC layers I–VI in schizophrenia (both in situ and qPCR), with greatest deficit in layer II (67%). Layer II SST mRNA+ neuron density was reduced in schizophrenia (~29%). PV mRNA was reduced in layers III (18%) and IV (31%) with no significant diagnostic difference in PV mRNA measured by qPCR. FASR mRNA was increased in schizophrenia (34%). SST, but not PV, expression correlated negatively with FASR and TNFSF13 expressions and with IWMN density. Conclusions: Our study demonstrates that SST interneurons are predominantly linked to the inhibitory interneuron pathology in the OFC in schizophrenia and that increased death receptor signaling mRNAs relate to prominent laminar deficits in SST mRNA in the OFC in schizophrenia. We suggest that SST interneurons may be more vulnerable to increased death receptor signaling than PV interneurons. PMID:27336026

  15. Macroscopic connection of rat insular cortex: anatomical bases underlying its physiological functions.

    PubMed

    Kobayashi, Masayuki

    2011-01-01

    The insular cortex (IC), which lies on the dorsal bank of the rhinal fissure, receives multi-modal sensory inputs, i.e. visceral, gustatory, nociceptive and thermal information from the sensory thalamic nuclei. In contrast to other primary sensory cortices such as visual, auditory and somatosensory areas, the anatomical features of the IC are quite distinctive; more than a half of the IC is composed of agranular or dysgranular cortex, which lacks a complete granular layer (layer IV). In addition to the characteristic layer structures, the IC has dense reciprocal innervations with the limbic structures, including the amygdala and hypothalamus. Such connectivity implies that sensory information processed in the IC is profoundly related to limbic information. By enabling the visualization of functional connectivity in the central nervous system, recent advancements in optical imaging techniques have opened the possibility to elucidate the mechanisms of sensory information processing from a macroscopic perspective. In this review, anatomical and functional features of the IC are overviewed from the aspect of gustatory processing, a typical sensation processed in the IC. In addition, the recently developed optical imaging techniques and their findings in gustatory information processing are summarized. We discuss how these characteristic features of excitatory propagation in the IC play functional roles in transmitting neural excitation arising from the limbic structures to the frontal and orbital cortices. PMID:21708315

  16. D-Cycloserine acts via increasing the GluN1 protein expressions in the frontal cortex and decreases the avoidance and risk assessment behaviors in a rat traumatic stress model.

    PubMed

    Sarıdoğan, Gökçe Elif; Aykaç, Aslı; Cabadak, Hülya; Cerit, Cem; Çalışkan, Mecit; Gören, M Zafer

    2015-10-15

    D-cycloserine (DCS), an FDA approved anti-tuberculosis drug has extensively been studied for its cognitive enhancer effects in psychiatric disorders. DCS may enhance the effects of fear extinction trainings in animals during exposure therapy and hence we investigated the effects of DCS on distinct behavioral parameters in a predator odor stress model and tested the optimal duration for repeated daily administrations of the agent. Cat fur odor blocks were used to produce stress and avoidance and risk assessment behavioral parameters were used where DCS or saline were used as treatments in adjunct to extinction trainings. We observed that DCS facilitated extinction training by providing further extinction of avoidance responses, risk assessment behaviors and increased the contact with the cue in a setting where DCS was administered before extinction trainings for 3 days without producing a significant tolerance. In amygdala and hippocampus, GluN1 protein expressions decreased 72h after the fear conditioning in the traumatic stress group suggesting a possible down-regulation of NMDARs. We observed that extinction learning increased GluN1 proteins both in the amygdaloid complex and the dorsal hippocampus of the rats receiving extinction training or extinction training with DCS. Our findings also indicate that DCS with extinction training increased GluN1 protein levels in the frontal cortex. We may suggest that action of DCS relies on enhancement of the consolidation of fear extinction in the frontal cortex. PMID:26225843

  17. Combined omega-3 fatty acids, aerobic exercise and cognitive stimulation prevents decline in gray matter volume of the frontal, parietal and cingulate cortex in patients with mild cognitive impairment.

    PubMed

    Köbe, Theresa; Witte, A Veronica; Schnelle, Ariane; Lesemann, Anne; Fabian, Sonja; Tesky, Valentina A; Pantel, Johannes; Flöel, Agnes

    2016-05-01

    Previous studies in older adults suggested beneficial effects of omega-3 fatty acid (FA) supplementation, aerobic exercise, or cognitive stimulation on brain structure and function. However, combined effects of these interventions in patients suffering from mild cognitive impairment (MCI) are unknown. Using a randomized interventional design, we evaluated the effect of combined omega-3 FA supplementation, aerobic exercise and cognitive stimulation (target intervention) versus omega-3 FA supplementation and non-aerobic exercise (control intervention) on cognitive function and gray matter volume in patients with MCI. Moreover, we analyzed potential vascular, metabolic or inflammatory mechanisms underlying these effects. Twenty-two MCI patients (8 females; 60-80years) successfully completed six months of omega-3 FA intake, aerobic cycling training and cognitive stimulation (n=13) or omega-3 FA intake and non-aerobic stretching and toning (n=9). Before and after the interventions, cognitive performance, magnetic resonance imaging of the brain at 3T (n=20), intima-media thickness of the internal carotid artery and serum markers of glucose control, lipid and B-vitamin metabolism, and inflammation were assessed. Intervention-related changes in gray matter volume of Alzheimer's disease (AD)-related brain regions, i.e., frontal, parietal, temporal and cingulate cortex were examined using voxel-based morphometry of high resolution T1-weighted images. After the intervention period, significant differences emerged in brain structure between groups: Gray matter volume decreased in the frontal, parietal and cingulate cortex of patients in the control intervention, while gray matter volume in these areas was preserved or even increased after the target intervention. Decreases in homocysteine levels in the target intervention group were associated with increases in gray matter volume in the middle frontal cortex (p=0.010). No significant differences in cognitive performance or

  18. 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

    PubMed Central

    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

  19. 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.

    PubMed

    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

  20. Dissociable attentional and inhibitory networks of dorsal and ventral areas of the right inferior frontal cortex: a combined task-specific and coordinate-based meta-analytic fMRI study.

    PubMed

    Sebastian, Alexandra; Jung, Patrick; Neuhoff, Jonathan; Wibral, Michael; Fox, Peter T; Lieb, Klaus; Fries, Pascal; Eickhoff, Simon B; Tüscher, Oliver; Mobascher, Arian

    2016-04-01

    The right inferior frontal cortex (rIFC) is frequently activated during executive control tasks. Whereas the function of the dorsal portion of rIFC, more precisely the inferior frontal junction (rIFJ), is convergingly assigned to the attention system, the functional key role of the ventral portion, i.e., the inferior frontal gyrus (rIFG), is hitherto controversially debated. Here, we used a two-step methodical approach to clarify the differential function of rIFJ and rIFG. First, we used event-related functional magnetic resonance imaging (fMRI) during a modified stop signal task with an attentional capture condition (acSST) to delineate attentional from inhibitory motor processes (step 1). Then, we applied coordinate-based meta-analytic connectivity modeling (MACM) to assess functional connectivity profiles of rIFJ and rIFG across various paradigm classes (step 2). As hypothesized, rIFJ activity was associated with the detection of salient stimuli, and was functionally connected to areas of the ventral and dorsal attention network. RIFG was activated during successful response inhibition even when controlling for attentional capture and revealed the highest functional connectivity with core motor areas. Thereby, rIFJ and rIFG delineated largely independent brain networks for attention and motor control. MACM results attributed a more specific attentional function to rIFJ, suggesting an integrative role between stimulus-driven ventral and goal-directed dorsal attention processes. In contrast, rIFG was disclosed as a region of the motor control but not attention system, being essential for response inhibition. The current study provides decisive evidence regarding a more precise functional characterization of rIFC subregions in attention and inhibition. PMID:25637472

  1. Dissociable Roles of Right Inferior Frontal Cortex and Anterior Insula in Inhibitory Control: Evidence from Intrinsic and Task-Related Functional Parcellation, Connectivity, and Response Profile Analyses across Multiple Datasets

    PubMed Central

    Ryali, Srikanth; Chen, Tianwen; Li, Chiang-Shan R.

    2014-01-01

    The right inferior frontal cortex (rIFC) and the right anterior insula (rAI) have been implicated consistently in inhibitory control, but their differential roles are poorly understood. Here we use multiple quantitative techniques to dissociate the functional organization and roles of the rAI and rIFC. We first conducted a meta-analysis of 70 published inhibitory control studies to generate a commonly activated right fronto-opercular cortex volume of interest (VOI). We then segmented this VOI using two types of features: (1) intrinsic brain activity; and (2) stop-signal task-evoked hemodynamic response profiles. In both cases, segmentation algorithms identified two stable and distinct clusters encompassing the rAI and rIFC. The rAI and rIFC clusters exhibited several distinct functional characteristics. First, the rAI showed stronger intrinsic and task-evoked functional connectivity with the anterior cingulate cortex, whereas the rIFC had stronger intrinsic and task-evoked functional connectivity with dorsomedial prefrontal and lateral fronto-parietal cortices. Second, the rAI showed greater activation than the rIFC during Unsuccessful, but not Successful, Stop trials, and multivoxel response profiles in the rAI, but not the rIFC, accurately differentiated between Successful and Unsuccessful Stop trials. Third, activation in the rIFC, but not rAI, predicted individual differences in inhibitory control abilities. Crucially, these findings were replicated in two independent cohorts of human participants. Together, our findings provide novel quantitative evidence for the dissociable roles of the rAI and rIFC in inhibitory control. We suggest that the rAI is particularly important for detecting behaviorally salient events, whereas the rIFC is more involved in implementing inhibitory control. PMID:25355218

  2. Correlation between number of type 2 serotonin receptors in the frontal cortex and intensity of serotonin-induced head jerks in mice

    SciTech Connect

    Popova, N.K.; Kulikov, A.V.; Pak, D.F.

    1986-02-01

    This paper shows interlinear differences discovered in the number of S2 receptors in the cerebral cortex and they are compared with the intensity of 5-HT-induced head jerking in mice of inbred lines. The number of S2 receptors was estimated from the quantity of tritium-spiperone, which is specifically bound by brain membrane preparations. Specific binding was assessed as the difference between the quantity of label bound in the absence and in the presence of methylsergide, a drug which specificably blocks S2 receptors. The presence of high correlation be= tween the number of S2 receptors and the number of head jerkings in mice reflects a genetic connection between this form of behavior and the serotonin system, and it in no way signifies that this phenomenon is controlled purely by the serotonin system and cannot be modulated by other mediator systems, for example, the adrenergic system.

  3. Temperament trait Harm Avoidance associates with μ-opioid receptor availability in frontal cortex: a PET study using [(11)C]carfentanil.

    PubMed

    Tuominen, Lauri; Salo, Johanna; Hirvonen, Jussi; Någren, Kjell; Laine, Pauliina; Melartin, Tarja; Isometsä, Erkki; Viikari, Jorma; Raitakari, Olli; Keltikangas-Järvinen, Liisa; Hietala, Jarmo

    2012-07-01

    Harm Avoidance is a temperament trait that associates with sensitivity to aversive and non-rewarding stimuli, higher anticipated threat and negative emotions during stress as well as a higher risk for affective disorders. The neurobiological correlates of interindividual differences in Harm Avoidance are largely unknown. We hypothesized that variability in Harm Avoidance trait would be explained by differences in the activity of μ-opioid system as the opioid system is known to regulate affective states and stress sensitivity. Brain μ-opioid receptor availability was measured in 22 healthy subjects using positron emission tomography and [(11)C]carfentanil, a selective μ-opioid receptor agonist. The subjects were selected from a large Finish population-based cohort (N=2075) on the basis of their pre-existing Temperament and Character Scores. Subjects scoring consistently in the upper (10) and lower (12) quartiles for the Harm Avoidance trait were studied. High Harm Avoidance score associated with high μ-opioid receptor availability (i.e. lower endogenous μ-opioid drive) in anterior cingulate cortex, ventromedial and dorsolateral prefrontal cortices and anterior insular cortex. These associations were driven by two subscales of Harm Avoidance; Shyness with Strangers and Fatigability and Asthenia. In conclusion, higher Harm Avoidance score in healthy subjects is associated with higher μ-opioid availability in regions involved in the regulation of anxiety as well as in the control of emotions, affective component of pain and interoceptive awareness. The results have relevance in the research of vulnerability factors for affective disorders. PMID:22484309

  4. Similarities in the behavior and molecular deficits in the frontal cortex between the neurotensin receptor subtype 1 knockout mice and chronic phencyclidine-treated mice: relevance to schizophrenia.

    PubMed

    Li, Zhimin; Boules, Mona; Williams, Katrina; Gordillo, Andres; Li, Shuhua; Richelson, Elliott

    2010-11-01

    Much evidence suggests that targeting the neurotensin (NT) system may provide a novel and promising treatment for schizophrenia. Our recent work shows that: NTS1 knockout (NTS1(-/-)) mice may provide a potential animal model for studying schizophrenia by investigating the effect of deletion NTS1 receptor on amphetamine-induced hyperactivity and neurochemical changes. The data indicate a hyper-dopaminergic state similar to the excessive striatal DA activity reported in schizophrenia. The present study was done to determine if NTS1(-/-) mice also have similar changes in behavior, in prefrontal neurotransmitters, and in protein expression, as observed in wild type (WT) mice treated with the psychotomimetic phencylclidine (PCP), an animal model for schizophrenia. Our results showed many similarities between untreated NTS1(-/-) mice and WT mice chronically treated with PCP (as compared with untreated WT mice): 1) lower PCP-induced locomotor activity; 2) similar avolition-like behavior in forced-swim test and tail suspension test; 3) lower prefrontal glutamate levels; 4) less PCP-induced dopamine release in medial prefrontal cortex (mPFC); and 5) down-regulation of mRNA and protein for DA D(1), DA D(2), and NMDAR2A in mPFC. Therefore, these data strengthen the hypothesis that the NTS1(-/-) mouse is an animal model of schizophrenia, particularly for the dysfunction of the prefrontal cortex. In addition, after chronic PCP administration, the DA D(1) receptor was up-regulated in NTS1(-/-) mice, results which suggest a possible interaction of NTS1/DA D(1) in mPFC contributing to chronic PCP-induced schizophrenia-like signs. PMID:20659557

  5. First evidence of overlaps between HIV-Associated Dementia (HAD) and non-viral neurodegenerative diseases: proteomic analysis of the frontal cortex from HIV+ patients with and without dementia

    PubMed Central

    2010-01-01

    Background The pathogenesis of HIV-associated dementia (HAD) is poorly understood. To date, detailed proteomic fingerprinting directly from autopsied brain tissues of HAD and HIV non-dementia patients has not been performed. Result Here, we have analyzed total proteins from the frontal cortex of 9 HAD and 5 HIV non-dementia patients. Using 2-Dimensional differential in-gel electrophoresis (2-DIGE) to analyze the brain tissue proteome, 76 differentially expressed proteins (p < 0.05; fold change>1.25) were identified between HAD and HIV non-dementia patients, of which 36 protein spots (based on 3D appearance of spots on the images) were chosen for the mass spectrometry analysis. The large majority of identified proteins were represented in the energy metabolic (mitochondria) and signal transduction pathways. Furthermore, over 90% of the protein candidates are common to both HAD and other non-viral neurodegenerative disease, such as Alzheimer's disease. The data was further validated using specific antibodies to 4 proteins (CA2, GS, CKMT and CRMP2) by western blot (WB) in the same samples used for 2D-DIGE, with additional confirmation by immunohistochemitsry (IHC) using frontal lobe tissue from different HAD and HIV+ non-dementia patients. The validation for all 4 antibodies by WB and IHC was in concordance with the DIGE results, lending further credence to the current findings. Conclusion These results suggest not only convergent pathogenetic pathways for the two diseases but also the possibility of increased Alzheimer's disease (AD) susceptibility in HAD patients whose life expectancy has been significantly increased by highly active antiretroviral therapy. PMID:20573273

  6. A comparison of multiple-unit activity in the medial prefrontal and agranular insular cortices during Pavlovian heart rate conditioning in rabbits.

    PubMed

    Gibbs, C M; Prescott, L B; Powell, D A

    1992-01-01

    Multiple-unit activity (MUA) was recorded from chronically implanted electrodes in the medial prefrontal cortex (PFCm) and the agranular insular cortex (Iag) in separate groups of rabbits during habituation training, followed by aversive Pavlovian conditioning and subsequent extinction training. Control animals received explicitly unpaired presentations of the tone conditioned stimulus (CS) and eye-shock unconditioned stimulus (US). Both the cardiac orientating reflex and the conditioned heart rate response (HR CR) consisted of bradycardia, whereas tone-evoked tachycardia was observed in animals that received unpaired stimuli. Short-latency (less than 20-60 ms), tone-evoked increases in PFCm MUA were observed during the initial trials of habituation training, with their magnitude declining predictably across repeated tone-alone presentations. Subsequent CS/US pairings, however, served systematically to reinstate and enhance this CS-evoked MUA, while both non-associative (unpaired CS/US) and extinction (CS alone) training resulted in significant attenuation of such activity. Unconditioned tone-evoked increases in MUA were also observed in the Iag during habituation; however, such unit responses appeared to be more variable than their PFCm counterparts and were of considerably lesser magnitude. Moreover, in striking contrast to the above PFCm findings, conditioning and non-associative training did not differentially affect overall mean evoked MUA in the Iag, although different post-tone patterns of activity were obtained with the two procedures. The contrasting training effects observed in animals with PFCm vs. Iag electrode placements did not appear to be attributable to differences in regional sensitivity to the US, since excitatory patterns of MUA were elicited by unsignalled presentations of eye-shock at most placements within each cortical field. Accordingly, the present findings are consistent with our previous lesion data in suggesting that, although training

  7. Neuregulin-1 (Nrg1) signaling has a preventive role and is altered in the frontal cortex under the pathological conditions of Alzheimer's disease.

    PubMed

    Jiang, Qiong; Chen, Shuangxi; Hu, Chengliang; Huang, Peizhi; Shen, Huifan; Zhao, Weijiang

    2016-09-01

    Alzheimer's disease (AD), one of the neurodegenerative disorders that may develop in the elderly, is characterized by the deposition of β‑amyloid protein (Aβ) and extensive neuronal cell death in the brain. Neuregulin‑1 (Nrg1)‑mediated intercellular and intracellular communication via binding to ErbB receptors regulates a diverse set of biological processes involved in the development of the nervous system. In the present study, a linear correlation was identified between Nrg1 and phosphorylated ErbB (pNeu and pErbB4) receptors in a human cortical tissue microarray. In addition, increased expression levels of Nrg1, but reduced pErbB receptor levels, were detected in the frontal lobe of a patient with AD. Western blotting and immunofluorescence staining were subsequently performed to uncover the potential preventive role of Nrg1 in cortical neurons affected by the neurodegenerative processes of AD. It was observed that the expression of Nrg1 increased as the culture time of the cortical neurons progressed. In addition, H2O2 and Aβ1‑42, two inducers of oxidative stress and neuronal damage, led to a dose‑dependent decrease in Nrg1 expression. Recombinant Nrg1β, however, was revealed to exert a pivotal role in preventing oxidative stress and neuronal damage from occurring in the mouse cortical neurons. Taken together, these results suggest that changes in Nrg1 signaling may influence the pathological development of AD, and exogenous Nrg1 may serve as a potential candidate for the prevention and treatment of AD. PMID:27486021

  8. Neuregulin-1 (Nrg1) signaling has a preventive role and is altered in the frontal cortex under the pathological conditions of Alzheimer's disease

    PubMed Central

    Jiang, Qiong; Chen, Shuangxi; Hu, Chengliang; Huang, Peizhi; Shen, Huifan; Zhao, Weijiang

    2016-01-01

    Alzheimer's disease (AD), one of the neurodegenerative disorders that may develop in the elderly, is characterized by the deposition of β-amyloid protein (Aβ) and extensive neuronal cell death in the brain. Neuregulin-1 (Nrg1)-mediated intercellular and intracellular communication via binding to ErbB receptors regulates a diverse set of biological processes involved in the development of the nervous system. In the present study, a linear correlation was identified between Nrg1 and phosphorylated ErbB (pNeu and pErbB4) receptors in a human cortical tissue microarray. In addition, increased expression levels of Nrg1, but reduced pErbB receptor levels, were detected in the frontal lobe of a patient with AD. Western blotting and immunofluorescence staining were subsequently performed to uncover the potential preventive role of Nrg1 in cortical neurons affected by the neurodegenerative processes of AD. It was observed that the expression of Nrg1 increased as the culture time of the cortical neurons progressed. In addition, H2O2 and Aβ1–42, two inducers of oxidative stress and neuronal damage, led to a dose-dependent decrease in Nrg1 expression. Recombinant Nrg1β, however, was revealed to exert a pivotal role in preventing oxidative stress and neuronal damage from occurring in the mouse cortical neurons. Taken together, these results suggest that changes in Nrg1 signaling may influence the pathological development of AD, and exogenous Nrg1 may serve as a potential candidate for the prevention and treatment of AD. PMID:27486021

  9. Quantitative Proteomic Analysis of the Orbital Frontal Cortex in Rats Following Extended Exposure to Caffeine Reveals Extensive Changes to Protein Expression: Implications for Neurological Disease.

    PubMed

    Franklin, Jane L; Mirzaei, Mehdi; Wearne, Travis A; Homewood, Judi; Goodchild, Ann K; Haynes, Paul A; Cornish, Jennifer L

    2016-05-01

    Caffeine is a plant-derived psychostimulant and a common additive found in a wide range of foods and pharmaceuticals. The orbitofrontal cortex (OFC) is rapidly activated by flavours, integrates gustatory and olfactory information, and plays a critical role in decision-making, with dysfunction contributing to psychopathologies and neurodegenerative conditions. This study investigated whether long-term consumption of caffeine causes changes to behavior and protein expression in the OFC. Male adult Sprague-Dawley rats (n = 8 per group) were treated for 26 days with either water or a 0.6 g/L caffeine solution. Locomotor behavior was measured on the first and last day of treatment, then again after 9 days treatment free following exposure to a mild stressor. When tested drug free, caffeine-treated animals were hyperactive compared to controls. Two hours following final behavioral testing, brains were rapidly removed and prepared for proteomic analysis of the OFC. Label free shotgun proteomics found 157 proteins differentially expressed in the caffeine-drinking rats compared to control. Major proteomic effects were seen for cell-to-cell communication, cytoskeletal regulation, and mitochondrial function. Similar changes have been observed in neurological disorders including Alzheimer's disease, Parkinson's disease, and schizophrenia. PMID:26941107

  10. Contrasting effects of the imidazol(in)e alpha 2-adrenoceptor agonists, medetomidine, clonidine and UK 14,304 on extraneuronal levels of noradrenaline in the rat frontal cortex: evaluation using in vivo microdialysis and synaptosomal uptake studies.

    PubMed Central

    Dalley, J W; Stanford, S C

    1995-01-01

    1. In vivo microdialysis in halothane-anaesthetized rats and synaptosomal [3H]-noradrenaline uptake studies in vitro were used to evaluate the effects of imidazole (medetomidine) and imidazoline (clonidine and UK 14,304) alpha 2-adrenoceptor agonists on extraneuronal levels of noradrenaline in the frontal cortex. 2. Levels of noradrenaline in the dialysate were increased by a depolarizing concentration of K+ (60 mM for 20 min) and substantially attenuated by reducing Ca2+ supply in the perfusate. These results suggest that spontaneous efflux of noradrenaline in the cortex is regulated predominantly by cation-dependent exocytotic mechanisms. 3. At a low perfusion concentration (0.5 microM), medetomidine, clonidine and UK 14,304 all reduced the level of noradrenaline in cortical dialysates. Continuous perfusion of the selective alpha 2-adrenoceptor antagonist, atipamezole (0.5 microM) caused a sustained increase in noradrenaline efflux and reversed the inhibitory effects of medetomidine. All these changes are consistent with drug actions at presynaptic alpha 2-adrenoceptors. 4. Higher concentrations of medetomidine (5-50 microM), but not clonidine or UK 14,304, evoked a non-desensitizing increase in noradrenaline efflux. This effect was not antagonized by 0.5 microM atipamezole. 5. The tricyclic noradrenaline reuptake inhibitor, desmethylimipramine (0.5-50 microM), increased noradrenaline efflux in a concentration-dependent manner. 6. The specific uptake of [3H]-noradrenaline into cortical synaptosomes was inhibited by medetomidine and desmethylimipramine with IC50 values of approximately 7 microM and 8 microM respectively. Neither clonidine nor UK 14,304 inhibited [3H]-noradrenaline uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7599940

  11. Comparison of effect of sex hormone manipulation during neonatal period, on mRNA expression of Slc9a4, Nr3c2, Htr5b and Mas1 in hippocampus and frontal cortex of male and female rats.

    PubMed

    Karimi, B; Hafidzi, M N; Panandam, J M; Fuzina, N H

    2013-01-01

    It has long been known that spatial memory and the ability to navigate through space are sexually dimorphic traits among mammals, and numerous studies have shown that these traits can be altered by means of sex hormone manipulation. Hippocampus, the main organ involved in this kind of memory, has specific signature genes with high expression level compared to other regions of the brain. Based on their expression levels and the role that products of these genes can play in processes like signal transduction, mediation of hormone effects and long term potentiation, these genes can be considered as genes necessary for routine tasks of hippocampus. Male and female rat pups were injected with estradiol and testosterone respectively. at early stage of their lives to examine the effect of sex hormone manipulation on mRNA expression of Slc9a4, Nr3c2, Htr5b and Mas1 using comparative quantitative real-time polymerase chain reaction. The results showed that expressions of these genes are strongly influenced by sex hormones in both the frontal cortex and hippocampus, especially in male hippocampus, in which expression of all genes were up-regulated. Htr5b was the only gene that was affected only in the males. Expression of Mas1 was contrary to expectations, showed stronger changes in its expression in cortex than in hippocampus. Nr3c2 was down regulated in all samples but up regulated in male hippocampus, and Slc9a4 also showed a huge up-regulation in male hippocampus compared to other samples. PMID:24152851

  12. Epigenetic age of the pre-frontal cortex is associated with neuritic plaques, amyloid load, and Alzheimer’s disease related cognitive functioning

    PubMed Central

    Levine, Morgan E.; Lu, Ake T.; Bennett, David A.; Horvath, Steve

    2015-01-01

    There is an urgent need to develop molecular biomarkers of brain age in order to advance our understanding of age related neurodegeneration. Recently, we developed a highly accurate epigenetic biomarker of tissue age (known as epigenetic clock) which is based on DNA methylation levels. Here we use n=700 dorsolateral prefrontal cortex (DLPFC) samples from Caucasian subjects of the Religious Order Study and the Rush Memory and Aging Project to examine the association between epigenetic age and Alzheimer’s disease (AD) related cognitive decline, and AD related neuropathological markers. Epigenetic age acceleration of DLPFC is correlated with several neuropathological measurements including diffuse plaques (r=0.12, p=0.0015), neuritic plaques (r=0.11, p=0.0036), and amyloid load (r=0.091, p=0.016). Further, it is associated with a decline in global cognitive functioning (β=−0.500, p=0.009), episodic memory (β=−0.411, p=0.009) and working memory (β=−0.405, p=0.011) among individuals with AD. The neuropathological markers may mediate the association between epigenetic age and cognitive decline. Genetic complex trait analysis (GCTA) revealed that epigenetic age acceleration is heritable (h2=0.41) and has significant genetic correlations with diffuse plaques (r=0.24, p=0.010) and possibly working memory (r=−0.35, p=0.065). Overall, these results suggest that the epigenetic clock may lend itself as a molecular biomarker of brain age. PMID:26684672

  13. T’ain’t what you say, it’s the way that you say it – left insula and inferior frontal cortex work in interaction with superior temporal regions to control the performance of vocal impersonations

    PubMed Central

    McGettigan, Carolyn; Eisner, Frank; Agnew, Zarinah K; Manly, Tom; Wisbey, Duncan; Scott, Sophie K

    2014-01-01

    Historically, the study of human identity perception has focused on faces, but the voice is also central to our expressions and experiences of identity (P. Belin, Fecteau, & Bedard, 2004). Our voices are highly flexible and dynamic; talkers speak differently depending on their health, emotional state, and the social setting, as well as extrinsic factors such as background noise. However, to date, there have been no studies of the neural correlates of identity modulation in speech production. In the current fMRI experiment, we measured the neural activity supporting controlled voice change in adult participants performing spoken impressions. We reveal that deliberate modulation of vocal identity recruits the left anterior insula and inferior frontal gyrus, supporting the planning of novel articulations. Bilateral sites in posterior superior temporal/inferior parietal cortex and a region in right mid/anterior superior temporal sulcus showed greater responses during the emulation of specific vocal identities than for impressions of generic accents. Using functional connectivity analyses, we describe roles for these three sites in their interactions with the brain regions supporting speech planning and production. Our findings mark a significant step toward understanding the neural control of vocal identity, with wider implications for the cognitive control of voluntary motor acts. PMID:23691984

  14. Investigation of neural correlates between perception of pain and hemodynamic response measured in the pre-frontal cortex using functional near infra-red spectroscopy

    NASA Astrophysics Data System (ADS)

    Krishnamurthy, Venkatagiri

    Perception of pain is multi-dimensional, comprising three major psychological dimensions: sensory-discriminative, motivational-affective and cognitive-evaluative. This dissertation study investigates the cognitive evaluation of pain, by acquiring functional Near Infra-Red Spectroscopic (fNIRS) measurements from the prefrontal cortex (PFC) areas, during mechanical and thermal pain stimulation induced on the subject's volar forearm. Clustered-wise analysis on the oxy-hemoglobin (HbO) response from specific PFC areas was followed by categorizing the resulting HbO response into early (0.1--12sec) and late (12.1--25sec) phases. For each respective phase, regression analysis was carried between the HbO-derived parameters and behaviorally measured pain rating. The major findings of this study include: (1) across both 41°C and 48°C thermal stimulation, significant DeltaHbO deactivation was observed during the late phase, in the left hemispheric (LH) anterior PFC (aPFC) or Brodmann area 10 (BA 10). (2) Significant correlates of pain rating were observed in the LH prefrontal areas: (a) under mechanical stimulation, early phase HbO-derived peak intensity (PI) from LH aPFC correlated with the pain rating. (b) Under both 41°C and 48°C thermal stimulation, late phase HbO-derived PI from the LH dorsolateral PFC (DLPFC or BA 46) showed correlation with the pain rating. (3) The significant correlates observed from the right hemispheric (RH) PFC were: (a) under mechanical stimulation, early phase HbO-derived FWHM from the RH aPFC correlated with the pain rating. (b) Under 41°C thermal stimulation, late phase HbO-derived PI from the RH DLPFC area correlated with the pain rating. (4) The late phase HbO-derived time to peak from LH aPFC reflected cognitive discrimination of two different pain levels (41°C and 48°C). The observed trend for DeltaHbO activation and deactivation could possibly be due to synaptic-induced vasodilation and vasoconstriction leading to increased or

  15. Automated MRI parcellation of the frontal lobe

    PubMed Central

    Ranta, Marin E.; Chen, Min; Crocetti, Deana; Prince, Jerry L.; Subramaniam, Krish; Fischl, Bruce; Kaufmann, Walter E.; Mostofsky, Stewart H.

    2014-01-01

    Examination of associations between specific disorders and physical properties of functionally relevant frontal lobe sub-regions is a fundamental goal in neuropsychiatry. Here we present and evaluate automated methods of frontal lobe parcellation with the programs FreeSurfer(FS) and TOADS-CRUISE(T-C), based on the manual method described in Ranta et al. (2009) in which sulcal-gyral landmarks were used to manually delimit functionally relevant regions within the frontal lobe: i.e., primary motor cortex, anterior cingulate, deep white matter, premotor cortex regions (supplementary motor complex, frontal eye field and lateral premotor cortex) and prefrontal cortex (PFC) regions (medial PFC, dorsolateral PFC, inferior PFC, lateral orbitofrontal cortex (OFC) and medial OFC). Dice's coefficient, a measure of overlap, and percent volume difference were used to measure the reliability between manual and automated delineations for each frontal lobe region. For FS, mean Dice's coefficient for all regions was 0.75 and percent volume difference was 21.2%. For T-C the mean Dice's coefficient was 0.77 and the mean percent volume difference for all regions was 20.2%. These results, along with a high degree of agreement between the two automated methods (mean Dice's coefficient = 0.81, percent volume difference = 12.4%) and a proof-of-principle group difference analysis that highlights the consistency and sensitivity of the automated methods, indicate that the automated methods are valid techniques for parcellation of the frontal lobe into functionally relevant sub-regions. Thus, the methodology has the potential to increase efficiency, statistical power and reproducibility for population analyses of neuropsychiatric disorders with hypothesized frontal lobe contributions. PMID:23897577

  16. Dissociations in Hippocampal and Frontal Contributions to Episodic Memory Performance

    PubMed Central

    Kramer, Joel H.; Rosen, Howard J.; Du, An-Tao; Schuff, Norbert; Hollnagel, Caroline; Weiner, Michael W.; Miller, Bruce L.; Delis, Dean C.

    2007-01-01

    The hippocampus and frontal lobes both contribute to episodic memory performance. In the present study, the authors evaluated the relative contributions of hippocampus, frontal lobes, anterior temporal cortex, and posterior cortex to memory performance in neurodegenerative patients and normal older controls. Subjects (n = 42) were studied with structural MRI and a memory paradigm that measured delayed recall, semantic clustering during recall, recognition discriminability, and recognition response bias. Data were analyzed with multiple regression. Consistent with the authors’ hypotheses, hippocampal volumes were the best predictor of delayed recall and recognition discriminability, whereas frontal volumes were the best predictor of semantic clustering and response bias. Smaller frontal volumes were associated with less semantic clustering during recall and a more liberal response bias. Results indicate that hippocampal and frontal contributions to episodic memory can be dissociated, with the hippocampus more important for memory accuracy, and frontal structures more important for strategic processing and decision making. PMID:16351355

  17. Common medial frontal mechanisms of adaptive control in humans and rodents

    PubMed Central

    Frank, Michael J.; Laubach, Mark

    2013-01-01

    In this report, we describe how common brain networks within the medial frontal cortex facilitate adaptive behavioral control in rodents and humans. We demonstrate that low frequency oscillations below 12 Hz are dramatically modulated after errors in humans over mid-frontal cortex and in rats within prelimbic and anterior cingulate regions of medial frontal cortex. These oscillations were phase-locked between medial frontal cortex and motor areas in both rats and humans. In rats, single neurons that encoded prior behavioral outcomes were phase-coherent with low-frequency field oscillations particularly after errors. Inactivating medial frontal regions in rats led to impaired behavioral adjustments after errors, eliminated the differential expression of low frequency oscillations after errors, and increased low-frequency spike-field coupling within motor cortex. Our results describe a novel mechanism for behavioral adaptation via low-frequency oscillations and elucidate how medial frontal networks synchronize brain activity to guide performance. PMID:24141310

  18. Human frontal lobes are not relatively large.

    PubMed

    Barton, Robert A; Venditti, Chris

    2013-05-28

    One of the most pervasive assumptions about human brain evolution is that it involved relative enlargement of the frontal lobes. We show that this assumption is without foundation. Analysis of five independent data sets using correctly scaled measures and phylogenetic methods reveals that the size of human frontal lobes, and of specific frontal regions, is as expected relative to the size of other brain structures. Recent claims for relative enlargement of human frontal white matter volume, and for relative enlargement shared by all great apes, seem to be mistaken. Furthermore, using a recently developed method for detecting shifts in evolutionary rates, we find that the rate of change in relative frontal cortex volume along the phylogenetic branch leading to humans was unremarkable and that other branches showed significantly faster rates of change. Although absolute and proportional frontal region size increased rapidly in humans, this change was tightly correlated with corresponding size increases in other areas and whole brain size, and with decreases in frontal neuron densities. The search for the neural basis of human cognitive uniqueness should therefore focus less on the frontal lobes in isolation and more on distributed neural networks. PMID:23671074

  19. Human frontal lobes are not relatively large

    PubMed Central

    Barton, Robert A.; Venditti, Chris

    2013-01-01

    One of the most pervasive assumptions about human brain evolution is that it involved relative enlargement of the frontal lobes. We show that this assumption is without foundation. Analysis of five independent data sets using correctly scaled measures and phylogenetic methods reveals that the size of human frontal lobes, and of specific frontal regions, is as expected relative to the size of other brain structures. Recent claims for relative enlargement of human frontal white matter volume, and for relative enlargement shared by all great apes, seem to be mistaken. Furthermore, using a recently developed method for detecting shifts in evolutionary rates, we find that the rate of change in relative frontal cortex volume along the phylogenetic branch leading to humans was unremarkable and that other branches showed significantly faster rates of change. Although absolute and proportional frontal region size increased rapidly in humans, this change was tightly correlated with corresponding size increases in other areas and whole brain size, and with decreases in frontal neuron densities. The search for the neural basis of human cognitive uniqueness should therefore focus less on the frontal lobes in isolation and more on distributed neural networks. PMID:23671074

  20. Architectonic Distribution of the Serotonin Transporter within the Orbitofrontal Cortex of the Vervet Monkey

    PubMed Central

    Way, Baldwin M.; Laćan, Goran; Fairbanks, Lynn A.; Melega, William P.

    2007-01-01

    To elucidate the organization of the serotoninergic innervation within the orbitofrontal cortex (OFC), serotonin transporter (SERT) density was quantified by autoradiography using [3H]cyanoimipramine binding. In six adult vervet monkeys, 15 architectonic areas were delineated according to cytoarchitectonic (Nissl), myeloarchitectonic (Gallyas) and chemoarchitectonic (Acetylcholinesterase) criteria to assess SERT distribution at two levels of organization: cortical area and cortical type. For cortical type, the 15 areas were evenly divided into three different categories primarily based upon the degree of granularization of layer IV: agranular, dysgranular, and granular. Within agranular and dysgranular, but not granular cortical types, SERT density was area-specific and progressively decreased in a medial to lateral gradient. Across cortical types, SERT density decreased in a caudal to rostral gradient: agranular > dysgranular > granular. A similar caudal to rostral gradient was seen when serotonin content was measured (using HPLC) in areas representative of each cortical type. Collectively, these results suggest that the serotoninergic innervation is organized according to both cortical type and area, and is thus structured to differentially modulate information processing within the OFC. PMID:17766046

  1. The Role of Human Parietal Cortex in Attention Networks

    ERIC Educational Resources Information Center

    Han, Shihui; Jiang, Yi; Gu, Hua; Rao, Hengyi; Mao, Lihua; Cui, Yong; Zhai, Renyou

    2004-01-01

    The parietal cortex has been proposed as part of the neural network for guiding spatial attention. However, it is unclear to what degree the parietal cortex contributes to the attentional modulations of activities of the visual cortex and the engagement of the frontal cortex in the attention network. We recorded behavioural performance and…

  2. The insular cortex: a review.

    PubMed

    Nieuwenhuys, Rudolf

    2012-01-01

    The human insular cortex forms a distinct, but entirely hidden lobe, situated in the depth of the Sylvian fissure. Here, we first review the recent literature on the connectivity and the functions of this structure. It appears that this small lobe, taking up less than 2% of the total cortical surface area, receives afferents from some sensory thalamic nuclei, is (mostly reciprocally) connected with the amygdala and with many limbic and association cortical areas, and is implicated in an astonishingly large number of widely different functions, ranging from pain perception and speech production to the processing of social emotions. Next, we embark on a long, adventurous journey through the voluminous literature on the structural organization of the insular cortex. This journey yielded the following take-home messages: (1) The meticulous, but mostly neglected publications of Rose (1928) and Brockhaus (1940) are still invaluable for our understanding of the architecture of the mammalian insular cortex. (2) The relation of the insular cortex to the adjacent claustrum is neither ontogenetical nor functional, but purely topographical. (3) The insular cortex has passed through a spectacular progressive differentiation during hominoid evolution, but the assumption of Craig (2009) that the human anterior insula has no homologue in the rhesus monkey is untenable. (4) The concept of Mesulam and Mufson (1985), that the primate insula is essentially composed of three concentrically arranged zones, agranular, dysgranular, and granular, is presumably correct, but there is at present much confusion concerning the more detailed architecture of the anterior insular cortex. (5) The large spindle-shaped cells in the fifth layer of the insular cortex, currently known as von Economo neurons (VENs), are not only confined to large-brained mammals, such as whales, elephants, apes, and humans, but also occur in monkeys and prosimians, as well as in the pygmy hippopotamus, the Atlantic

  3. Jealousy increased by induced relative left frontal cortical activity.

    PubMed

    Kelley, Nicholas J; Eastwick, Paul W; Harmon-Jones, Eddie; Schmeichel, Brandon J

    2015-10-01

    Asymmetric frontal cortical activity may be one key to the process linking social exclusion to jealous feelings. The current research examined the causal role of asymmetric frontal brain activity in modulating jealousy in response to social exclusion. Transcranial direct-current stimulation (tDCS) over the frontal cortex to manipulate asymmetric frontal cortical activity was combined with a modified version of the Cyberball paradigm designed to induce jealousy. After receiving 15 min of tDCS, participants were excluded by a desired partner and reported how jealous they felt. Among individuals who were excluded, tDCS to increase relative left frontal cortical activity caused greater levels of self-reported jealousy compared to tDCS to increase relative right frontal cortical activity or sham stimulation. Limitations concerning the specificity of this effect and implications for the role of the asymmetric prefrontal cortical activity in motivated behaviors are discussed. PMID:25844975

  4. Rat whisker motor cortex is subdivided into sensory-input and motor-output areas

    PubMed Central

    Smith, Jared B.; Alloway, Kevin D.

    2013-01-01

    Rodent whisking is an exploratory behavior that can be modified by sensory feedback. Consistent with this, many whisker-sensitive cortical regions project to agranular motor [motor cortex (MI)] cortex, but the relative topography of these afferent projections has not been established. Intracortical microstimulation (ICMS) evokes whisker movements that are used to map the functional organization of MI, but no study has compared the whisker-related inputs to MI with the ICMS sites that evoke whisker movements. To elucidate this relationship, anterograde tracers were placed in posterior parietal cortex (PPC) and in the primary somatosensory (SI) and secondary somatosensory (SII) cortical areas so that their labeled projections to MI could be analyzed with respect to ICMS sites that evoke whisker movements. Projections from SI and SII terminate in a narrow zone that marks the transition between the medial agranular (AGm) and lateral agranular (AGl) cortical areas, but PPC projects more medially and terminates in AGm proper. Paired recordings of MI neurons indicate that the region between AGm and AGl is highly responsive to whisker deflections, but neurons in AGm display negligible responses to whisker stimulation. By contrast, AGm microstimulation is more effective in evoking whisker movements than microstimulation of the transitional region between AGm and AGl. The AGm region was also found to contain a larger concentration of corticotectal neurons, which could convey whisker-related information to the facial nucleus. These results indicate that rat whisker MI is comprised of at least two functionally distinct subregions: a sensory processing zone in the transitional region between AGm and AGl, and a motor-output region located more medially in AGm proper. PMID:23372545

  5. Retrosplenial cortex in the rhesus monkey: a cytoarchitectonic and Golgi study.

    PubMed

    Vogt, B A

    1976-09-01

    The laminar and cellular structure of retrosplenial cortex in the rhesus monkey was studied with Nissl stained and rapid Golgi impregnated tissue and the results were used to evaluate morphological features of a cortical transition zone. The granular layer of retrosplenial granular cortex is composed primarily of small, density packed, star pyramidal cells. These cells branch within the granular layer itself, while the apical dendrite enters layer I where it branches infrequently or not at all. This cell type is similar to the star pyramid first described by Lorente de No except in its areal and laminar distribution. Cytoarchitectonic observations of retrosplenial agranular cortex show, that, although this area is relatively "agranular" in comparison to other cortical areas, it does possess an incipient layer II and layer IV. These layers are composed mainly of small and medium sized pyramidal cells, but many non-pyramidal cell types were found in these and other layers in this area in rapid Golgi preparations. Stellate cells with beaded or smooth, lightly spinous dendrites were found throughout layer I-IV, while fusiform cells with smooth or very lightly spinous dendrites appear in layers III-VI. Areas surrounding retrosplenial cortex in the posterior cingulate region were also evaluated in Nissl and Golgi preparations including the indusium griseum, subiculum (dorsal to the corpus callosum) and area 23. The laminar and cellular constitutents of retrosplenial cortex were then evaluated in the context of cortical architectonic transition. The transition from one cellular layer in the indusium griseum to five cellular layers in area 23 is made by the addition of layers II, III, IV and VI in retrosplenial cortex to the one ganglionic layer of the indusium griseum and subiculum. Besides the addition and subdivision of layers in retrosplenial cortex, two aspects of cell morphology were found to change in this region. First, the structure of pyramidal cells

  6. Specific frontal neural dynamics contribute to decisions to check

    PubMed Central

    Stoll, Frederic M.; Fontanier, Vincent; Procyk, Emmanuel

    2016-01-01

    Curiosity and information seeking potently shapes our behaviour and are thought to rely on the frontal cortex. Yet, the frontal regions and neural dynamics that control the drive to check for information remain unknown. Here we trained monkeys in a task where they had the opportunity to gain information about the potential delivery of a large bonus reward or continue with a default instructed decision task. Single-unit recordings in behaving monkeys reveal that decisions to check for additional information first engage midcingulate cortex and then lateral prefrontal cortex. The opposite is true for instructed decisions. Importantly, deciding to check engages neurons also involved in performance monitoring. Further, specific midcingulate activity could be discerned several trials before the monkeys actually choose to check the environment. Our data show that deciding to seek information on the current state of the environment is characterized by specific dynamics of neural activity within the prefrontal cortex. PMID:27319361

  7. The effect of age on cognitive performance of frontal patients

    PubMed Central

    Cipolotti, Lisa; Healy, Colm; Chan, Edgar; MacPherson, Sarah E.; White, Mark; Woollett, Katherine; Turner, Martha; Robinson, Gail; Spanò, Barbara; Bozzali, Marco; Shallice, Tim

    2015-01-01

    Age is known to affect prefrontal brain structure and executive functioning in healthy older adults, patients with neurodegenerative conditions and TBI. Yet, no studies appear to have systematically investigated the effect of age on cognitive performance in patients with focal lesions. We investigated the effect of age on the cognitive performance of a large sample of tumour and stroke patients with focal unilateral, frontal (n=68), or non-frontal lesions (n=45) and healthy controls (n=52). We retrospectively reviewed their cross sectional cognitive and imaging data. In our frontal patients, age significantly predicted the magnitude of their impairment on two executive tests (Raven's Advanced Progressive Matrices, RAPM and the Stroop test) but not on nominal (Graded Naming Test, GNT) or perceptual (Incomplete Letters) task. In our non-frontal patients, age did not predict the magnitude of their impairment on the RAPM and GNT. Furthermore, the exacerbated executive impairment observed in our frontal patients manifested itself from middle age. We found that only age consistently predicted the exacerbated executive impairment. Lesions to specific frontal areas, or an increase in global brain atrophy or white matter abnormalities were not associated with this impairment. Our results are in line with the notion that the frontal cortex plays a critical role in aging to counteract cognitive and neuronal decline. We suggest that the combined effect of aging and frontal lesions impairs the frontal cortical systems by causing its computational power to fall below the threshold needed to complete executive tasks successfully. PMID:26102190

  8. The effect of age on cognitive performance of frontal patients.

    PubMed

    Cipolotti, Lisa; Healy, Colm; Chan, Edgar; MacPherson, Sarah E; White, Mark; Woollett, Katherine; Turner, Martha; Robinson, Gail; Spanò, Barbara; Bozzali, Marco; Shallice, Tim

    2015-08-01

    Age is known to affect prefrontal brain structure and executive functioning in healthy older adults, patients with neurodegenerative conditions and TBI. Yet, no studies appear to have systematically investigated the effect of age on cognitive performance in patients with focal lesions. We investigated the effect of age on the cognitive performance of a large sample of tumour and stroke patients with focal unilateral, frontal (n=68), or non-frontal lesions (n=45) and healthy controls (n=52). We retrospectively reviewed their cross sectional cognitive and imaging data. In our frontal patients, age significantly predicted the magnitude of their impairment on two executive tests (Raven's Advanced Progressive Matrices, RAPM and the Stroop test) but not on nominal (Graded Naming Test, GNT) or perceptual (Incomplete Letters) task. In our non-frontal patients, age did not predict the magnitude of their impairment on the RAPM and GNT. Furthermore, the exacerbated executive impairment observed in our frontal patients manifested itself from middle age. We found that only age consistently predicted the exacerbated executive impairment. Lesions to specific frontal areas, or an increase in global brain atrophy or white matter abnormalities were not associated with this impairment. Our results are in line with the notion that the frontal cortex plays a critical role in aging to counteract cognitive and neuronal decline. We suggest that the combined effect of aging and frontal lesions impairs the frontal cortical systems by causing its computational power to fall below the threshold needed to complete executive tasks successfully. PMID:26102190

  9. A cutaneous agranular CD2- CD4+ CD56+ "lymphoma": report of two cases and review of the literature.

    PubMed

    Kameoka, J; Ichinohasama, R; Tanaka, M; Miura, I; Tomiya, Y; Takahashi, S; Yamada, M; Ishikawa, I; Kadowaki, I; Sasaki, O; Kimura, J; Meguro, K; Ooya, K; Ito, S

    1998-10-01

    We report 2 cases of agranular CD2- CD4+ CD56+ non-Hodgkin lymphoma in which skin seemed to be the primary site. A 21-year-old woman's initial symptom was a skin nodule on the right cheek. She also had tumors in the nasopharynx, and the bone marrow subsequently became involved. No lymphadenopathy was present. She experienced complete remission after dose-intensified therapy with cyclophosphamide, hydroxydaunomycin, vincristine [Oncovin], and prednisone (CHOP), but the disease relapsed in the central nervous system 6 months later. An 81-year-old man experienced an 11-month history of skin nodules in the left forearm. On admission, he had a bone marrow infiltration of lymphoma cells. He died of pneumonia during chemotherapy. The malignant cells of the 2 patients had similar morphologic features, with a monocytoid nucleus and no cytoplasmic granules. The cells in both cases showed a unique phenotype: CD2-, CD3-, CD4+, CD8-, CD13-, CD14-, CD34-, CD16-, CD56+, CD57-, HLA-DR-positive. Staining for peroxidase and alpha-naphthyl butyrate esterase was negative. The T-cell receptor beta, gamma, delta, IgH, kappa, lambda genes were of germ line configurations. The DNA of Epstein-Barr virus was not detected from the bone marrow cells by polymerase chain reaction. Only 3 other cases with similar phenotypes have been reported; all had skin lesions. Although the origin of these cells remains unknown, we propose that this is a distinct clinicopathologic entity. PMID:9763034

  10. The orbitofrontal cortex: novelty, deviation from expectation, and memory.

    PubMed

    Petrides, Michael

    2007-12-01

    The orbitofrontal cortex is strongly connected with limbic areas of the medial temporal lobe that are critically involved in the establishment of declarative memories (entorhinal and perirhinal cortex and the hippocampal region) as well as the amygdala and the hypothalamus that are involved in emotional and motivational states. The present article reviews evidence regarding the role of the orbitofrontal cortex in the processing of novel information, breaches of expectation, and memory. Functional neuroimaging evidence is provided that there is a difference between the anterior and posterior orbitofrontal cortex in such processing. Exposure to novel information gives rise to a selective increase of activity in the granular anterior part of the orbitofrontal cortex (area 11) and this activity increases when subjects attempt to encode this information in memory. If the stimuli violate expectations (e.g., inspection of graffiti-like stimuli in the context of other regular stimuli) or are unpleasant (i.e., exposure to the sounds of car crashes), there is increased response in the posteromedial agranular/dysgranular area 13 of the orbitofrontal region. The anatomic data provide a framework within which to understand these functional neuroimaging findings. PMID:17872393

  11. MRI volumetry of prefrontal cortex

    NASA Astrophysics Data System (ADS)

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

    1995-05-01

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

  12. Charting the Maturation of the Frontal Lobe: An Electrophysiological Strategy

    ERIC Educational Resources Information Center

    Segalowitz, S. J.; Davies, Patricia L.

    2004-01-01

    Tracking the functional development of specific regions of the prefrontal cortex in children using event-related potentials (ERPs) is challenging for both technical and conceptual reasons. In this paper we outline our strategy for studying frontal lobe development and present preliminary results from children aged 7-17 years and young adults using…

  13. Dynamic Variation in Pleasure in Children Predicts Nonlinear Change in Lateral Frontal Brain Electrical Activity

    ERIC Educational Resources Information Center

    Light, Sharee N.; Coan, James A.; Frye, Corrina; Goldsmith, H. Hill; Davidson, Richard J.

    2009-01-01

    Individual variation in the experience and expression of pleasure may relate to differential patterns of lateral frontal activity. Brain electrical measures have been used to study the asymmetric involvement of lateral frontal cortex in positive emotion, but the excellent time resolution of these measures has not been used to capture…

  14. Developmental Alterations of Frontal-Striatal-Thalamic Connectivity in Obsessive-Compulsive Disorder

    ERIC Educational Resources Information Center

    Fitzgerald, Kate Dimond; Welsh, Robert C.; Stern, Emily R.; Angstadt, Mike; Hanna, Gregory L.; Abelson, James L.; Taylor, Stephan F.

    2011-01-01

    Objective: Pediatric obsessive-compulsive disorder is characterized by abnormalities of frontal-striatal-thalamic circuitry that appear near illness onset and persist over its course. Distinct frontal-striatal-thalamic loops through cortical centers for cognitive control (anterior cingulate cortex) and emotion processing (ventral medial frontal…

  15. Frontal delta event-related oscillations relate to frontal volume in mild cognitive impairment and healthy controls.

    PubMed

    Yener, Görsev G; Emek-Savaş, Derya Durusu; Lizio, Roberta; Çavuşoğlu, Berrin; Carducci, Filippo; Ada, Emel; Güntekin, Bahar; Babiloni, Claudio C; Başar, Erol

    2016-05-01

    Amnesic mild cognitive impairment (MCI) represents a risk of developing Alzheimer's disease (AD), but not all MCI subjects progress to dementia of AD type. Magnetic resonance imaging (MRI) of cortical and hippocampal atrophy supports early diagnosis of AD in MCI subjects, while frontal event-related oscillations (EROs) at delta frequencies (<4Hz) are appealing markers for this purpose, as they are both cost-effective and largely available. The present study tested the hypothesis that these EROs reflect cortical frontal neurodegeneration in the continuum between normal and amnesic MCI subjects. EROs and volumetric MRI data were recorded in 28 amnesic MCI and in 28 healthy elderly controls (HCs). EROs were collected during a standard visual oddball paradigm including frequent (66.6%) and rare (33.3%; targets to be mentally counted) stimuli. Peak-to-peak amplitude of delta target EROs (<4Hz) was measured. Volume of frontal cortex was estimated from MRIs. Frontal volume was lower in MCI compared to the HC group. Furthermore, widespread delta target EROs were lower in amplitude in the former than in the latter group. Finally, there was a positive correlation between frontal volume and frontal delta target EROs in MCI and HC subjects as a whole group. These results suggest that frontal delta EROs reflect frontal neurodegeneration in the continuum between normal and amnesic MCI subjects. PMID:25660300

  16. Differential frontal involvement in shifts of internal and perceptual attention

    PubMed Central

    Tanoue, Ryan T.; Jones, Kevin T.; Peterson, Dwight J.; Berryhill, Marian E.

    2012-01-01

    Background Perceptual attention enhances the processing of items in the environment, whereas internal attention enhances processing of items encoded in visual working memory. In perceptual and internal attention cueing paradigms, cues indicate the to-be-probed item before (pre-cueing) or after (retro-cueing) the memory display, respectively. Pre- and retro- cues confer similar behavioral accuracy benefits (pre-: 14–19%, retro-: 11–17%) and neuroimaging data show that they activate overlapping frontoparietal networks (1). Yet reports of behavioral and neuroimaging differences suggest that pre- and retro-cueing differentially recruit frontal and parietal cortices (1). Objective/Hypothesis This study examined whether perceptual and internal attention are equally disrupted by neurostimulation to frontal and parietal cortices. We hypothesized that neurostimulation applied to frontal cortex would disrupt internal attention to a greater extent than perceptual attention. Methods Cathodal transcranial direct current stimulation (tDCS) was applied to frontal or parietal cortices. After stimulation, participants completed a change detection task coupled with either pre- or retro- cues. Results Cathodal tDCS across site (frontal, parietal) hindered performance. However, frontal tDCS had a greater negative impact on the retro-cued trials demonstrating greater frontal involvement during shifts of internal attention. Conclusions These results complement the neuroimaging data and provide further evidence suggesting that perceptual and internal attention are not identical processes. We conclude that although internal and perceptual attention are mediated by similar frontoparietal networks, the weight of contribution of these structures differs, with internal attention relying more heavily on the frontal cortex. PMID:23266133

  17. A Novel Role for the Rat Retrosplenial Cortex in Cognitive Control

    ERIC Educational Resources Information Center

    Nelson, Andrew J. D.; Hindley, Emma L.; Haddon, Josephine E.; Vann, Seralynne D.; Aggleton, John P.

    2014-01-01

    By virtue of its frontal and hippocampal connections, the retrosplenial cortex is uniquely placed to support cognition. Here, we tested whether the retrosplenial cortex is required for frontal tasks analogous to the Stroop Test, i.e., for the ability to select between conflicting responses and inhibit responding to task-irrelevant cues. Rats first…

  18. Frontal Fibrosing Alopecia.

    PubMed

    Holmes, S

    2016-07-01

    Frontal fibrosing alopecia, described just over 20 years ago, has become one of the most frequently seen causes of scarring alopecia at many specialist hair clinics. Considered a clinical variant of lichen planopilaris (LPP), it has distinctive features and associations which distinguish it from LPP. Although largely affecting postmenopausal women, a small but increasing number of men and premenopausal women are affected. The spectrum of the disease has expanded from involvement of the frontal hairline and eyebrows, to potentially affecting the entire hairline, facial and body hair. Genetic and environmental factors have been implicated but the aetiology remains uncertain. A range of treatments have been used in management of the condition, but clinical trials are required to establish effectiveness. PMID:27388531

  19. Frontal Polymerization in Microgravity

    NASA Technical Reports Server (NTRS)

    Pojman, John A.

    1999-01-01

    Frontal polymerization systems, with their inherent large thermal and compositional gradients, are greatly affected by buoyancy-driven convection. Sounding rocket experiments allowed the preparation of benchmark materials and demonstrated that methods to suppress the Rayleigh-Taylor instability in ground-based research did not significantly affect the molecular weight of the polymer. Experiments under weightlessness show clearly that bubbles produced during the reaction interact very differently than under 1 g.

  20. [Frontal mucocele: open surgery].

    PubMed

    Pia, F; Aluffi, P; Borello, G

    1999-06-01

    This work presents 13 cases of frontal mucoceles, 9 with endo-orbital extension. All were treated with 'open surgery': 11 using a fronto-orbital approach, 2 with a bicoronal Cairns-Unterberger approach. Four patients had recurrent mucoceles 1-20 years after the previous surgery. In one case there was an association with frontal osteoma. In 10 cases, conservative treatment was applied through repermeabilization of the infundibular region through an external, endonasal pathway and positioning of a nasal sinus drainage tube (kept in place for 4 weeks). In the remaining 3 cases, the sinus cavity was obliterated with autologous abdominal fat. This choice was made because of the presence of osteomyelitic foci, in one case mucopioceles, or by the widespread dural exposure encountered during the course of surgery. Two cases of post-operative sinus reinfection were encountered: one underwent surgical revision, the other was an orbital site recurrence arising 7 years after previous surgical obliteration of the frontal sinus. The esthetic result was unsatisfactory in 2 patients treated with a trans-facial approach. Ten patients were disease free after an average 56 months of follow-up. Although functional endoscopic surgery undoubtedly makes it possible to achieve excellent results in the treatment of most sinus mucoceles, open surgery remains a valid procedure in frontal mucoceles with orbital and/or endocranial extension and in cases where the district anatomy is unfavorable for a purely endonasal approach. The indications and limitations of open surgery are critically discussed in the light of personal experience and current literature. PMID:10546373

  1. Developmental consequences of childhood frontal lobe damage.

    PubMed

    Eslinger, P J; Grattan, L M; Damasio, H; Damasio, A R

    1992-07-01

    A 33-year-old woman underwent neurologic and neuropsychological studies 26 years after she sustained damage to the frontal lobe. The findings of the neurologic examination were normal, and magnetic resonance imaging revealed a lesion in left prefrontal cortex and deep white matter. Cerebral blood flow studies showed an abnormal pattern in both left and right frontal regions. The patient exhibited striking neuropsychological defects in higher cognition, most notably in self-regulation of emotion and affect and in social behavior. Analysis of her behavioral development failed to yield a pattern of abrupt onset of defect immediately after the lesion occurred. On the contrary, there was a delayed onset of defects, followed by a period of seeming progression, and finally an arrest of development in adolescence. We suggest that this peculiar pattern is the natural consequence of the varied changes that occurred in brain development and social cognition during the patient's formative years. While certain long-term neuropsychological deficits in our case are similar to those following frontal damage in adults, the delayed onset and progression of deficits are different. PMID:1497505

  2. Role of Frontal Alpha Oscillations in Creativity

    PubMed Central

    Lustenberger, Caroline; Boyle, Michael R.; Foulser, A. Alban; Mellin, Juliann M.; Fröhlich, Flavio

    2015-01-01

    Creativity, the ability to produce innovative ideas, is a key higher-order cognitive function that is poorly understood. At the level of macroscopic cortical network dynamics, recent EEG data suggests that cortical oscillations in the alpha frequency band (8 – 12 Hz) are correlated with creative thinking. However, whether alpha oscillations play a fundamental role in creativity has remained unknown. Here we show that creativity is increased by enhancing alpha power using 10 Hz transcranial alternating current stimulation (10Hz-tACS) of the frontal cortex. In a study of 20 healthy participants with a randomized, balanced cross-over design, we found a significant improvement of 7.4% in the Creativity Index measured by the Torrance Test of Creative Thinking, a comprehensive and most frequently used assay of creative potential and strengths. In a second similar study with 20 subjects, 40Hz-tACS was used in instead of 10Hz-tACS to rule out a general “electrical stimulation” effect. No significant change in the Creativity Index was found for such frontal gamma stimulation. Our results suggest that alpha activity in frontal brain areas is selectively involved in creativity; this enhancement represents the first demonstration of specific neuronal dynamics that drive creativity and can be modulated by non-invasive brain stimulation. Our findings agree with the model that alpha recruitment increases with internal processing demands and is involved in inhibitory top-down control, which is an important requirement for creative ideation. PMID:25913062

  3. Frontal and striatal alterations associated with psychopathic traits in adolescents

    PubMed Central

    Yang, Yaling; Narr, Katherine L.; Baker, Laura A.; Joshi, Shantanu H.; Jahanshad, Neda; Raine, Adrian; Thompson, Paul M.

    2016-01-01

    Neuroimaging research has demonstrated a range of structural deficits in adults with psychopathy, but little is known about structural correlates of psychopathic tendencies in adolescents. Here we examined structural magnetic resonance imaging (sMRI) data obtained from 14-year-old adolescents (n=108) using tensor-based morphometry (TBM) to isolate global and localized differences in brain tissue volumes associated with psychopathic traits in this otherwise healthy developmental population. We found that greater levels of psychopathic traits were correlated with increased brain tissue volumes in the left putamen, left ansa peduncularis, right superiomedial prefrontal cortex, left inferior frontal cortex, right orbitofrontal cortex, and right medial temporal regions and reduced brain tissues volumes in the right middle frontal cortex, left superior parietal lobule, and left inferior parietal lobule. Post hoc analyses of parcellated regional volumes also showed putamen enlargements to correlate with increased psychopathic traits. Consistent with earlier studies, findings suggest poor decision-making and emotional dysregulation associated with psychopathy may be due, in part, to structural anomalies in frontal and temporal regions whereas striatal structural variations may contribute to sensation-seeking and reward-driven behavior in psychopathic individuals. Future studies will help clarify how disturbances in brain maturational processes might lead to the developmental trajectory from psychopathic tendencies in adolescents to adult psychopathy. PMID:25676553

  4. Auditory connections and functions of prefrontal cortex

    PubMed Central

    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

  5. Instrumentation in Frontal Sinus Surgery.

    PubMed

    Tajudeen, Bobby A; Adappa, Nithin D

    2016-08-01

    Frontal recess dissection proposes many challenges to the surgeon. These challenges stem from its highly variable nature, small caliber, difficult visualization, and proximity to vital structures such as the skull base and orbit. As such, delicate mucosal-sparing dissection of the frontal recess with proper instrumentation is paramount to minimize scar formation and ensure patency. Here, the article explores key instrumentation in frontal recess surgery with an emphasis on hand instruments and adjunctive technologies. PMID:27329980

  6. Pediatric frontal mucocele secondary to a bifid frontal sinus septum.

    PubMed

    Plikaitis, Christina M; Purzycki, Adam R; Couture, Daniel; David, Lisa R

    2010-09-01

    A mucocele is a mucus-containing sac lined with epithelium that arises within a sinus when its drainage is compromised. The frontal sinus is the most common location, with frontal mucocele development occurring when the nasofrontal duct becomes obstructed because of polyps, bone tumors, prior surgery, sinusitis, trauma, or anatomic variation. We report an unusual case of a sterile pediatric frontal mucocele presenting as a slowly enlarging forehead mass due to a bifid frontal sinus septum. A 9-year-old girl presented to the craniofacial clinic for evaluation of a right frontal mass that had been slowly growing over the past year. She was otherwise healthy and had no history of previous trauma or sinus infections. Computed tomography (CT) scan results revealed a localized frontal fluid collection with protrusion and thinning of the anterior frontal bone between 2 midline bony septii. Surgical cranialization of the frontal sinus was performed. The anatomy of her lesion seen both on CT scan and intraoperatively likely explains this unusual case presentation. Instead of the usual inciting event of an intact frontal sinus drainage system becoming blocked, this patient seemed to have a primary developmental lack of any drainage system that led to her mucocele. During formation of her frontal sinus, she developed a bifid septum within the midline that excluded a portion of her frontal sinus from the lateral nasofrontal ducts. With mucus-producing epithelium trapped within these bony confines, pressure began to mount with expansion and thinning of the bone both anteriorly and posteriorly. The lack of any infectious symptoms and sterile culture results may support that this space developed primarily and was never in continuity with the external drainage system. Only 4 other patients have been reported with asymptomatic forehead swelling as the only presenting symptom, with the age ranging from 33 to 79 years. This patient represents the first clinical report of a congenital

  7. 1H MRSI of middle frontal gyrus in pediatric ADHD.

    PubMed

    Tafazoli, Sharwin; O'Neill, Joseph; Bejjani, Anthony; Ly, Ronald; Salamon, Noriko; McCracken, James T; Alger, Jeffry R; Levitt, Jennifer G

    2013-04-01

    Neuroimaging studies in multiple modalities have implicated the left or right dorsolateral prefrontal cortex (here, middle frontal gyrus) in attentional functions, in ADHD, and in dopamine agonist treatment of ADHD. The far lateral location of this cortex in the brain, however, has made it difficult to study with magnetic resonance spectroscopy (MRS). We used the smaller voxel sizes of the magnetic resonance spectroscopic imaging (MRSI) variant of MRS, acquired at a steep coronal-oblique angle to sample bilateral middle frontal gyrus in 13 children and adolescents with ADHD and 13 age- and sex-matched healthy controls. Within a subsample of the ADHD patients, aspects of attention were also assessed with the Trail Making Task. In right middle frontal gyrus only, mean levels of N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (tNAA), creatine + phosphocreatine (Cr), choline-compounds (Cho), and myo-inositol (mI) were significantly lower in the ADHD than in the control sample. In the ADHD patients, lower right middle frontal Cr was associated with worse performance on Trails A and B (focused attention, concentration, set-shifting), while the opposite relationship held true for the control group on Trails B. These findings add to evidence implicating right middle frontal cortex in ADHD. Lower levels of these multiple species may reflect osmotic adjustment to elevated prefrontal cortical perfusion in ADHD and/or a previously hypothesized defect in astrocytic production of lactate in ADHD resulting in decelerated energetic metabolism (Cr), membrane synthesis (Cho, mI), and acetyl-CoA substrate for NAA synthesis. Lower Cr levels may indicate attentional or executive impairments. PMID:23273650

  8. Frontal lobe neurology and the creative mind

    PubMed Central

    de Souza, Leonardo C.; Guimarães, Henrique C.; Teixeira, Antônio L.; Caramelli, Paulo; Levy, Richard; Dubois, Bruno; Volle, Emmanuelle

    2014-01-01

    Concepts from cognitive neuroscience strongly suggest that the prefrontal cortex (PFC) plays a crucial role in the cognitive functions necessary for creative thinking. Functional imaging studies have repeatedly demonstrated the involvement of PFC in creativity tasks. Patient studies have demonstrated that frontal damage due to focal lesions or neurodegenerative diseases are associated with impairments in various creativity tasks. However, against all odds, a series of clinical observations has reported the facilitation of artistic production in patients with neurodegenerative diseases affecting PFC, such as frontotemporal dementia (FTD). An exacerbation of creativity in frontal diseases would challenge neuroimaging findings in controls and patients, as well as the theoretical role of prefrontal functions in creativity processes. To explore this paradox, we reported the history of a FTD patient who exhibited the emergence of visual artistic productions during the course of the disease. The patient produced a large amount of drawings, which have been evaluated by a group of professional artists who were blind to the diagnosis. We also reviewed the published clinical cases reporting a change in the artistic abilities in patients with neurological diseases. We attempted to reconcile these clinical observations to previous experimental findings by addressing several questions raised by our review. For instance, to what extent can the cognitive, conative, and affective changes following frontal damage explain changes in artistic abilities? Does artistic exacerbation truly reflect increased creative capacities? These considerations could help to clarify the place of creativity—as it has been defined and explored by cognitive neuroscience—in artistic creation and may provide leads for future lesion studies. PMID:25101029

  9. A parallel genome-wide mRNA and microRNA profiling of the frontal cortex of HIV patients with and without HIV-associated dementia shows the role of axon guidance and downstream pathways in HIV-mediated neurodegeneration

    PubMed Central

    2012-01-01

    Background HIV-associated dementia (HAD) is the most common dementia type in young adults less than 40 years of age. Although the neurotoxins, oxidative/metabolic stress and impaired activity of neurotrophic factors are believed to be underlying reasons for the development of HAD, the genomic basis, which ultimately defines the virus-host interaction and leads to neurologic manifestation of HIV disease is lacking. Therefore, identifying HIV fingerprints on the host gene machinery and its regulation by microRNA holds a great promise and potential for improving our understanding of HAD pathogenesis, its diagnosis and therapy. Results A parallel profiling of mRNA and miRNA of the frontal cortex autopsies from HIV positive patients with and without dementia was performed using Illumina Human-6 BeadChip and Affymetrix version 1.0 miRNA array, respectively. The gene ontology and pathway analysis of the two data sets showed high concordance between miRNA and mRNAs, revealing significant interference with the host axon guidance and its downstream signalling pathways in HAD brains. Moreover, the differentially expressed (DE) miRNAs identified in this study, in particular miR-137, 153 and 218, based on which most correlations were built cumulatively targeted neurodegeneration related pathways, implying their future potential in diagnosis, prognosis and possible therapies for HIV-mediated and possibly other neurodegenerative diseases. Furthermore, this relationship between DE miRNAs and DE mRNAs was also reflected in correlation analysis using Bayesian networks by splitting-averaging strategy (SA-BNs), which revealed 195 statistically significant correlated miRNA-mRNA pairs according to Pearson’s correlation test (P<0.05). Conclusions Our study provides the first evidence on unambiguous support for intrinsic functional relationship between mRNA and miRNA in the context of HIV-mediated neurodegeneration, which shows that neurologic manifestation in HIV patients possibly

  10. Distinctive Roles of 5-aza-2′-deoxycytidine in Anterior Agranular Insular and Basolateral Amygdala in Reconsolidation of Aversive Memory Associated with Morphine in Rats

    PubMed Central

    Liu, Peng; Zhang, JianJun; Li, Ming; Sui, Nan

    2016-01-01

    5-aza-2′-deoxycytidine (5-aza), an inhibitor of DNA methyltransferases (DNMTs), has been implicated in aversive memory and the function of brain region involved in processing emotion. However, little is known about the role of 5-aza in the reconsolidation of opiate withdrawal memory. In the present study, using the morphine-naloxone induced conditioned place aversion (CPA) model in rats, we injected 5-aza into agranular insular (AI), granular insular (GI), basolateral amygdala (BLA) and central amygdala (CeA) immediately after the memory retrieval and tested the behavioral consequences at 24 h, 7 and 14 days after retrieval test. We found that 5-aza injection into AI disrupted the reconsolidation of morphine-associated withdrawal memory, but 5-aza injection into GI had no impact on the reconsolidation. Meanwhile, 5-aza injection into BLA but not CeA attenuated the withdrawal memory trace 14 days later. However, 5-aza administration to rats, in the absence of memory reactivation, had no effect on morphine-associated withdrawal memory. These findings suggest that 5-aza interferes with the reconsolidation of opiate withdrawal memory, and the roles of insular and amygdala in reconsolidation are distinctive. PMID:27014010

  11. Distinct frontal lobe morphology in girls and boys with ADHD

    PubMed Central

    Dirlikov, Benjamin; Shiels Rosch, Keri; Crocetti, Deana; Denckla, Martha B.; Mahone, E. Mark; Mostofsky, Stewart H.

    2014-01-01

    Objective This study investigated whether frontal lobe cortical morphology differs for boys and girls with ADHD (ages 8–12 years) in comparison to typically developing (TD) peers. Method Participants included 226 children between the ages of 8–12 including 93 children with ADHD (29 girls) and 133 TD children (42 girls) for which 3T MPRAGE MRI scans were obtained. A fully automated frontal lobe atlas was used to generate functionally distinct frontal subdivisions, with surface area (SA) and cortical thickness (CT) assessed in each region. Analyses focused on overall diagnostic differences as well as examinations of the effect of diagnosis within boys and girls. Results Girls, but not boys, with ADHD showed overall reductions in total prefrontal cortex (PFC) SA. Localization revealed that girls showed widely distributed reductions in the bilateral dorsolateral PFC, left inferior lateral PFC, right medial PFC, right orbitofrontal cortex, and left anterior cingulate; and boys showed reduced SA only in the right anterior cingulate and left medial PFC. In contrast, boys, but not girls, with ADHD showed overall reductions in total premotor cortex (PMC) SA. Further localization revealed that in boys, premotor reductions were observed in bilateral lateral PMC regions; and in girls reductions were observed in bilateral supplementary motor complex. In line with diagnostic group differences, PMC and PFC SAs were inversely correlated with symptom severity in both girls and boys with ADHD. Conclusions These results elucidate sex-based differences in cortical morphology of functional subdivisions of the frontal lobe and provide additional evidence of associations among SA and symptom severity in children with ADHD. PMID:25610784

  12. Relative frontal brain asymmetry and cortisol release after social stress: The role of action orientation.

    PubMed

    Düsing, Rainer; Tops, Mattie; Radtke, Elise Leila; Kuhl, Julius; Quirin, Markus

    2016-03-01

    Social evaluation is a potent stressor and consistently leads to an activation of the hypothalamic-pituitary-adrenal system. Here, we investigated whether individual differences in action orientation influence the relationship between the cortisol response to social-evaluative threat and relative left frontal electroencephalographic (EEG) alpha asymmetry as a brain marker of approach motivation. Forty-nine participants were exposed to a camera-based variant of the Trier Social Stress Task while salivary cortisol and resting EEG frontal alpha asymmetry were assessed before and after stress induction. Higher relative left frontal activity was associated with higher changes in cortisol levels as measured by the area under curve with respect to increase, particularly in individuals low in action orientation. We discuss the role of the left frontal cortex in coping, the potential role of oxytocin, and negative health consequences when the left-frontal coping process becomes overstrained. PMID:26850008

  13. Finding prefrontal cortex in the rat.

    PubMed

    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. PMID:26867704

  14. Subspecialization in the human posterior medial cortex

    PubMed Central

    Bzdok, Danilo; Heeger, Adrian; Langner, Robert; Laird, Angela R.; Fox, Peter T.; Palomero-Gallagher, Nicola; Vogt, Brent A.; Zilles, Karl; Eickhoff, Simon B.

    2014-01-01

    The posterior medial cortex (PMC) is particularly poorly understood. Its neural activity changes have been related to highly disparate mental processes. We therefore investigated PMC properties with a data-driven exploratory approach. First, we subdivided the PMC by whole-brain coactivation profiles. Second, functional connectivity of the ensuing PMC regions was compared by task-constrained meta-analytic coactivation mapping (MACM) and task-unconstrained resting-state correlations (RSFC). Third, PMC regions were functionally described by forward/reverse functional inference. A precuneal cluster was mostly connected to the intraparietal sulcus, frontal eye fields, and right temporo-parietal junction; associated with attention and motor tasks. A ventral posterior cingulate cortex (PCC) cluster was mostly connected to the ventromedial prefrontal cortex and middle left inferior parietal cortex (IPC); associated with facial appraisal and language tasks. A dorsal PCC cluster was mostly connected to the dorsomedial prefrontal cortex, anterior/posterior IPC, posterior midcingulate cortex, and left dorsolateral prefrontal cortex; associated with delay discounting. A cluster in the retrosplenial cortex was mostly connected to the anterior thalamus and hippocampus. Furthermore, all PMC clusters were congruently coupled with the default mode network according to task-constrained but not task-unconstrained connectivity. We thus identified distinct regions in the PMC and characterized their neural networks and functional implications. PMID:25462801

  15. Frontal glutamate and reward processing in adolescence and adulthood.

    PubMed

    Gleich, Tobias; Lorenz, Robert C; Pöhland, Lydia; Raufelder, Diana; Deserno, Lorenz; Beck, Anne; Heinz, Andreas; Kühn, Simone; Gallinat, Jürgen

    2015-11-01

    The fronto-limbic network interaction, driven by glutamatergic and dopaminergic neurotransmission, represents a core mechanism of motivated behavior and personality traits. Reward seeking behavior undergoes tremendous changes in adolescence paralleled by neurobiological changes of this network including the prefrontal cortex, striatum and amygdala. Since fronto-limbic dysfunctions also underlie major psychiatric diseases beginning in adolescence, this investigation focuses on network characteristics separating adolescents from adults. To investigate differences in network interactions, the brain reward system activity (slot machine task) together with frontal glutamate concentration (anterior cingulate cortex, ACC) was measured in 28 adolescents and 26 adults employing functional magnetic resonance imaging and magnetic resonance spectroscopy, respectively. An inverse coupling of glutamate concentrations in the ACC and activation of the ventral striatum was observed in adolescents. Further, amygdala response in adolescents was negatively correlated with the personality trait impulsivity. For adults, no significant associations of network components or correlations with impulsivity were found. The inverse association between frontal glutamate concentration and striatal activation in adolescents is in line with the triadic model of motivated behavior stressing the important role of frontal top-down inhibition on limbic structures. Our data identified glutamate as the mediating neurotransmitter of this inhibitory process and demonstrates the relevance of glutamate on the reward system and related behavioral traits like impulsivity. This fronto-limbic coupling may represent a vulnerability factor for psychiatric disorders starting in adolescence but not in adulthood. PMID:25009315

  16. Individuals' and groups' intentions in the medial prefrontal cortex.

    PubMed

    Chaminade, Thierry; Kawato, Mitsuo; Frith, Chris

    2011-11-16

    Functional MRI signal was recorded while participants perceived stimuli presented using moving dots. In two conditions of interest, the motion of dots depicted intentions: dots representing the joints of an agent performing an action, and dots representing individual agents behaving contingently. The finding of a common cluster in the posterior part of the medial frontal cortex involved in intentional action representation validates the hypothesis that perception of these two conditions requires a similar internal representation. A cluster responding to the behaving group only is found in the anterior medial frontal cortex. These results support a division of the medial frontal cortex according to social stimuli attributes, with anterior areas responding to higher-order group behaviours integrating the action of multiple individual agents. PMID:21897305

  17. Perseverative Interference with Object-in-Place Scene Learning in Rhesus Monkeys with Bilateral Ablation of Ventrolateral Prefrontal Cortex

    ERIC Educational Resources Information Center

    Baxter, Mark G.; Browning, Philip G. F.; Mitchell, Anna S.

    2008-01-01

    Surgical disconnection of the frontal cortex and inferotemporal cortex severely impairs many aspects of visual learning and memory, including learning of new object-in-place scene memory problems, a monkey model of episodic memory. As part of a study of specialization within prefrontal cortex in visual learning and memory, we tested monkeys with…

  18. Point-light biological motion perception activates human premotor cortex.

    PubMed

    Saygin, Ayse Pinar; Wilson, Stephen M; Hagler, Donald J; Bates, Elizabeth; Sereno, Martin I

    2004-07-01

    Motion cues can be surprisingly powerful in defining objects and events. Specifically, a handful of point-lights attached to the joints of a human actor will evoke a vivid percept of action when the body is in motion. The perception of point-light biological motion activates posterior cortical areas of the brain. On the other hand, observation of others' actions is known to also evoke activity in motor and premotor areas in frontal cortex. In the present study, we investigated whether point-light biological motion animations would lead to activity in frontal cortex as well. We performed a human functional magnetic resonance imaging study on a high-field-strength magnet and used a number of methods to increase signal, as well as cortical surface-based analysis methods. Areas that responded selectively to point-light biological motion were found in lateral and inferior temporal cortex and in inferior frontal cortex. The robust responses we observed in frontal areas indicate that these stimuli can also recruit action observation networks, although they are very simplified and characterize actions by motion cues alone. The finding that even point-light animations evoke activity in frontal regions suggests that the motor system of the observer may be recruited to "fill in" these simplified displays. PMID:15240810

  19. Longitudinal progression of frontal and temporal lobe changes in schizophrenia.

    PubMed

    Cobia, Derin J; Smith, Matthew J; Wang, Lei; Csernansky, John G

    2012-08-01

    Cortical abnormalities are considered a neurobiological characteristic of schizophrenia. However, the pattern of such deficits as they progress over the illness remains poorly understood. The goal of this project was to assess the progression of cortical thinning in frontal and temporal cortical regions in schizophrenia, and determine whether relationships exist between them and neuropsychological and clinical symptom profiles. As part of a larger longitudinal 2-year follow-up study, schizophrenia (n=20) and healthy participants (n=20) group-matched for age, gender, and recent-alcohol use, were selected. Using MRI, estimates of gray matter thickness were derived from primary anatomical gyri of the frontal and temporal lobes using surface-based algorithms. These values were entered into repeated-measures analysis of variance models to determine group status and time effects. Change values in cortical regions were correlated with changes in neuropsychological functioning and clinical symptomatology. Results revealed exaggerated cortical thinning of the middle frontal, superior temporal, and middle temporal gyri in schizophrenia participants. These thickness changes strongly influenced volumetric reductions, but were not related to shrinking surface area. Neuropsychological and clinical symptom profiles were stable in the schizophrenia participants despite these neuroanatomic changes. Overall it appears that ongoing abnormalities in the cerebral cortex continue after initial onset of schizophrenia, particularly the lateral aspects of frontal and temporal regions, and do not relate to neuropsychological or clinical measures over time. Maintenance of neuropsychological performance and clinical stability in the face of changing neuroanatomical structure suggests the involvement of alternative compensatory mechanisms. PMID:22647883

  20. Genetic and Environmental Influences on Frontal EEG Asymmetry and Alpha Power in 9–10 Year Old Twins

    PubMed Central

    Gao, Yu; Tuvblad, Catherine; Raine, Adrian; Lozano, Dora I.; Baker, Laura A.

    2008-01-01

    Modest genetic influences on frontal EEG asymmetry have been found in adults, but little is known about its genetic origins in children. Resting frontal asymmetry and alpha power were examined in 951 9–10-year-old twins. Results showed that in both males and females: (1) a modest but significant amount of variance in frontal asymmetry was accounted for by genetic factors (11–27%) with the remainder accounted for by non-shared environmental influences, and (2) alpha power were highly heritable, with 70–85% of the variance accounted for by genetic factors. Results suggest that the genetic architecture of frontal asymmetry and alpha power in late childhood are similar to that in adulthood and that the high non-shared environmental influences on frontal asymmetry may reflect environmentally-influenced individual differences in the maturation of frontal cortex as well as state-dependent influences on specific measurements. PMID:19386046

  1. Role of Medio-Dorsal Frontal and Posterior Parietal Neurons during Auditory Detection Performance in Rats

    PubMed Central

    Bohon, Kaitlin S.; Wiest, Michael C.

    2014-01-01

    To further characterize the role of frontal and parietal cortices in rat cognition, we recorded action potentials simultaneously from multiple sites in the medio-dorsal frontal cortex and posterior parietal cortex of rats while they performed a two-choice auditory detection task. We quantified neural correlates of task performance, including response movements, perception of a target tone, and the differentiation between stimuli with distinct features (different pitches or durations). A minority of units—15% in frontal cortex, 23% in parietal cortex—significantly distinguished hit trials (successful detections, response movement to the right) from correct rejection trials (correct leftward response to the absence of the target tone). Estimating the contribution of movement-related activity to these responses suggested that more than half of these units were likely signaling correct perception of the auditory target, rather than merely movement direction. In addition, we found a smaller and mostly not overlapping population of units that differentiated stimuli based on task-irrelevant details. The detection-related spiking responses we observed suggest that correlates of perception in the rat are sparsely represented among neurons in the rat's frontal-parietal network, without being concentrated preferentially in frontal or parietal areas. PMID:25479194

  2. [Interneuronal frontal-amygdala interactions in cats trained for the quality of the reinforcement].

    PubMed

    Merzhanova, G Kh; Dolbakian, E E

    1998-01-01

    In eight cats the appetitive instrumental conditioned reflexes to light were elaborated by the method of "active choice" of reinforcement quality: the short-latency bar-pressing responses were reinforced with bread-meat mixture and the delayed responses were reinforced with meat. The animals differed in behavior strategy: six cats preferred the delayed pressings (the so-called "self-control" group), and two cats preferred the pressings with short delay (the so-called "impulsive" group). The multiunit activity in the basolateral amygdala and frontal cortex was recorded by chronically implanted nichrome semimicroelectrodes. The interactions of the neighboring neurons in the basolateral amygdala and the frontal cortex (within the local neuronal networks) and between the amygdalar and cortical neurons (distributed neuronal networks of amygdalar-frontal and fronto-amygdalar directions) were estimated by means of statistical crosscorrelation analysis of spike trains. The interneuronal cross-correlations were studied with delays in the range of 0-100 ms. The number of cross-correlations between the neuronal discharges both in the local and distributed networks was significantly higher in "impulsive" cats, mainly, with delays in the range of 0-30 ms. In both groups of animals the number of correlations was the highest during omissions of conditioned pressings, i.e., in cases of difficult choice of reinforcement. We suggest that the basolateral amygdala, frontal cortex, and amygdalar-frontal distributed neuronal networks are involved in the system of brain structures, which determine the individual features of animal behavior. PMID:9700904

  3. The relation of hedonic hunger and restrained eating to lateralized frontal activation.

    PubMed

    Winter, S R; Feig, E H; Kounios, J; Erickson, B; Berkowitz, S; Lowe, M R

    2016-09-01

    Asymmetrical alpha activation in the prefrontal cortex (frontal asymmetry) in electroencephalography (EEG) has been related to eating behavior. Prior studies linked dietary restraint with right frontal asymmetry [1] and disinhibition with left frontal asymmetry [2]. The current study simultaneously assessed restrained eating and hedonic hunger (drive for food reward in the absence of hunger) in relation to frontal asymmetry. Resting-state EEG and measures of restrained eating (Revised Restraint Scale; RRS) and hedonic hunger (Power of Food Scale; PFS) were assessed in 61 non-obese adults. Individually, hedonic hunger predicted left asymmetry. However, PFS and RRS were correlated (r=0.48, p<0.05) and there was a significant interaction between PFS and RRS on frontal asymmetry, p<0.01. Results indicated that those high in hedonic hunger exhibited left asymmetry irrespective of RRS scores; among those low in PFS, only those high in RRS showed right asymmetry. Results were consistent with literature linking avoidant behaviors (restraint) with right-frontal asymmetry and approach behaviors (binge eating) with left-frontal asymmetry. It appears that a strong drive toward palatable foods predominates at a neural level even when restraint is high. Findings suggest that lateralized frontal activity is an indicator of motivation both to consume and to avoid consuming highly palatable foods. PMID:27133731

  4. Effects of low-level microwave irradiation on hippocampal and frontal cortical choline uptake are classically conditionable

    SciTech Connect

    Lai, H.; Horita, A.; Chou, C.K.; Guy, A.W.

    1987-08-01

    In previous research, we found that sodium-dependent high-affinity choline uptake in the hippocampus and frontal cortex of the rat was lowered after acute (45 min) exposure to low-level 2450-MHz pulsed microwaves (power density 1 mW/cm2; average whole body specific absorption rate, 0.6 W/kg; 2 mu sec pulses, 500 pps). In the present experiment, we investigated developments of tolerance and classical conditioning to these effects of microwaves. Rats were exposed to microwaves in cylindrical waveguides in 10 daily sessions (45 min per session). In an 11th session, we subjected the rats to either microwave (study of tolerance) or sham exposure (study of conditioned effect) for 45 min, and immediately measured choline uptake in the hippocampus and frontal cortex. We found that tolerance, a decrease in response to microwaves, developed to the effect of microwaves on choline uptake in the hippocampus, but not in the frontal cortex. Conditioned effects were also observed: an increase in choline uptake in the hippocampus and a decrease in uptake in the frontal cortex. These data suggest that the effects of microwaves on choline uptake in the hippocampus and frontal cortex are classically conditionable, probably to cues in the exposure environment.

  5. Frontal theta as a mechanism for cognitive control

    PubMed Central

    Cavanagh, James F.; Frank, Michael J.

    2014-01-01

    Recent advancements in cognitive neuroscience have afforded a description of neural responses in terms of latent algorithmic operations. However, the adoption of this approach to human scalp EEG has been more limited, despite the ability of this methodology to quantify canonical neuronal processes. Here we provide evidence that theta band activities over the mid-frontal cortex appear to reflect a common computation used for realizing the need for cognitive control. Moreover, by virtue of inherent properties of field oscillations, these theta band processes may be used to communicate this need and subsequently implement such control across disparate brain regions. Frontal theta is thus a compelling candidate mechanism by which emergent processes such as ‘cognitive control’ may be biophysically realized. PMID:24835663

  6. Management of Frontal Sinus Tumors.

    PubMed

    Selleck, Anne Morgan; Desai, Dipan; Thorp, Brian D; Ebert, Charles S; Zanation, Adam M

    2016-08-01

    The most common primary tumors of the frontal sinus are osteomas and inverted papillomas, although a variety of other tumors involving this space have been reported. With the advent of new surgical techniques and instrumentation, an endoscopic approach to this region has become feasible. The preoperative assessment and decision making must take into account the complexity of frontal sinus anatomy, tumor type, tumor location, and associated attachments. These procedures allow adequate visualization, tumor removal, and postoperative monitoring, and preserve fairly normal sinus function. Open techniques may also be required and should be in the surgeon's armamentarium. PMID:27450620

  7. Premotor and parietal cortex: corticocortical connectivity and combinatorial computations.

    PubMed

    Wise, S P; Boussaoud, D; Johnson, P B; Caminiti, R

    1997-01-01

    The dorsal premotor cortex is a functionally distinct cortical field or group of fields in the primate frontal cortex. Anatomical studies have confirmed that most parietal input to the dorsal premotor cortex originates from the superior parietal lobule. However, these projections arise not only from the dorsal aspect of area 5, as has long been known, but also from newly defined areas of posterior parietal cortex, which are directly connected with the extrastriate visual cortex. Thus, the dorsal premotor cortex receives much more direct visual input than previously accepted. It appears that this fronto-parietal network functions as a visuomotor controller-one that makes computations based on proprioceptive, visual, gaze, attentional, and other information to produce an output that reflects the selection, preparation, and execution of movements. PMID:9056706

  8. Frontal-posterior theta oscillations reflect memory retrieval during sentence comprehension.

    PubMed

    Meyer, Lars; Grigutsch, Maren; Schmuck, Noura; Gaston, Phoebe; Friederici, Angela D

    2015-10-01

    Successful working-memory retrieval requires that items be retained as distinct units. At the neural level, it has been shown that theta-band oscillatory power increases with the number of to-be-distinguished items during working-memory retrieval. Here we hypothesized that during sentence comprehension, verbal-working-memory retrieval demands lead to increased theta power over frontal cortex, supposedly supporting the distinction amongst stored items during verbal-working-memory retrieval. Also, synchronicity may increase between the frontal cortex and the posterior cortex, with the latter supposedly supporting item retention. We operationalized retrieval by using pronouns, which refer to and trigger the retrieval of antecedent nouns from a preceding sentence part. Retrieval demand was systematically varied by changing the pronoun antecedent: Either, it was non-embedded in the preceding main clause, and thus easy-to-retrieve across a single clause boundary, or embedded in the preceding subordinate clause, and thus hard-to-retrieve across a double clause boundary. We combined electroencephalography (EEG), scalp-level time-frequency analysis, source localization, and source-level coherence analysis, observing a frontal-midline and broad left-hemispheric theta-power increase for embedded-antecedent compared to non-embedded-antecedent retrieval. Sources were localized to left-frontal, left-parietal, and bilateral-inferior-temporal cortices. Coherence analyses suggested synchronicity between left-frontal and left-parietal and between left-frontal and right-inferior-temporal cortices. Activity of an array of left-frontal, left-parietal, and bilateral-inferior-temporal cortices may thus assist retrieval during sentence comprehension, potentially indexing the orchestration of item distinction, verbal working memory, and long-term memory. Our results extend prior findings by mapping prior knowledge on the functional role of theta oscillations onto processes genuine to human

  9. Conceptual Models of Frontal Cyclones.

    ERIC Educational Resources Information Center

    Eagleman, Joe R.

    1981-01-01

    This discussion of weather models uses maps to illustrate the differences among three types of frontal cyclones (long wave, short wave, and troughs). Awareness of these cyclones can provide clues to atmospheric conditions which can lead toward accurate weather forecasting. (AM)

  10. Collaborative Writing: Online versus Frontal

    ERIC Educational Resources Information Center

    Passig, David; Schwartz, Gali

    2007-01-01

    Students in higher education, most frequently, use the frontal approach while being asked to collaborate on a writing assignment. However, the difficulty in collaborative writing using conventional technologies such as pen and paper, board or computer is the limited ability to view the work of your peers during the process (Baeker, Glass,…

  11. [Diagnostic dyspraxia and frontal syndrome].

    PubMed

    Donnet, A; Schmitt, A; Poncet, M

    1998-05-01

    A 27-year-old ambidexter woman experienced a clinical and psychometric frontal syndrome associated with a partial callosal syndrome following transcallosal surgery for an intraventricular neurocytoma. She also complained of difficulties with her left hand which realized a particular form of diagnostic dyspraxia: there were specific features of an isolated dysfunction of the control of the realization of a program. PMID:9773062

  12. Oscillatory dynamics coordinating human frontal networks in support of goal maintenance.

    PubMed

    Voytek, Bradley; Kayser, Andrew S; Badre, David; Fegen, David; Chang, Edward F; Crone, Nathan E; Parvizi, Josef; Knight, Robert T; D'Esposito, Mark

    2015-09-01

    Humans have a capacity for hierarchical cognitive control-the ability to simultaneously control immediate actions while holding more abstract goals in mind. Neuropsychological and neuroimaging evidence suggests that hierarchical cognitive control emerges from a frontal architecture whereby prefrontal cortex coordinates neural activity in the motor cortices when abstract rules are needed to govern motor outcomes. We utilized the improved temporal resolution of human intracranial electrocorticography to investigate the mechanisms by which frontal cortical oscillatory networks communicate in support of hierarchical cognitive control. Responding according to progressively more abstract rules resulted in greater frontal network theta phase encoding (4-8 Hz) and increased prefrontal local neuronal population activity (high gamma amplitude, 80-150 Hz), which predicts trial-by-trial response times. Theta phase encoding coupled with high gamma amplitude during inter-regional information encoding, suggesting that inter-regional phase encoding is a mechanism for the dynamic instantiation of complex cognitive functions by frontal cortical subnetworks. PMID:26214371

  13. Transient shifts in frontal and parietal circuits scale with enhanced visual feedback and changes in force variability and error

    PubMed Central

    Poon, Cynthia; Coombes, Stephen A.; Corcos, Daniel M.; Christou, Evangelos A.

    2013-01-01

    When subjects perform a learned motor task with increased visual gain, error and variability are reduced. Neuroimaging studies have identified a corresponding increase in activity in parietal cortex, premotor cortex, primary motor cortex, and extrastriate visual cortex. Much less is understood about the neural processes that underlie the immediate transition from low to high visual gain within a trial. This study used 128-channel electroencephalography to measure cortical activity during a visually guided precision grip task, in which the gain of the visual display was changed during the task. Force variability during the transition from low to high visual gain was characterized by an inverted U-shape, whereas force error decreased from low to high gain. Source analysis identified cortical activity in the same structures previously identified using functional magnetic resonance imaging. Source analysis also identified a time-varying shift in the strongest source activity. Superior regions of the motor and parietal cortex had stronger source activity from 300 to 600 ms after the transition, whereas inferior regions of the extrastriate visual cortex had stronger source activity from 500 to 700 ms after the transition. Force variability and electrical activity were linearly related, with a positive relation in the parietal cortex and a negative relation in the frontal cortex. Force error was nonlinearly related to electrical activity in the parietal cortex and frontal cortex by a quadratic function. This is the first evidence that force variability and force error are systematically related to a time-varying shift in cortical activity in frontal and parietal cortex in response to enhanced visual gain. PMID:23365186

  14. Vocalization Induced CFos Expression in Marmoset Cortex

    PubMed Central

    Miller, Cory T.; DiMauro, Audrey; Pistorio, Ashley; Hendry, Stewart; Wang, Xiaoqin

    2010-01-01

    All non-human primates communicate with conspecifics using vocalizations, a system involving both the production and perception of species-specific vocal signals. Much of the work on the neural basis of primate vocal communication in cortex has focused on the sensory processing of vocalizations, while relatively little data are available for vocal production. Earlier physiological studies in squirrel monkeys had shed doubts on the involvement of primate cortex in vocal behaviors. The aim of the present study was to identify areas of common marmoset (Callithrix jacchus) cortex that are potentially involved in vocal communication. In this study, we quantified cFos expression in three areas of marmoset cortexfrontal, temporal (auditory), and medial temporal – under various vocal conditions. Specifically, we examined cFos expression in these cortical areas during the sensory, motor (vocal production), and sensory–motor components of vocal communication. Our results showed an increase in cFos expression in ventrolateral prefrontal cortex as well as the medial and lateral belt areas of auditory cortex in the vocal perception condition. In contrast, subjects in the vocal production condition resulted in increased cFos expression only in dorsal premotor cortex. During the sensory–motor condition (antiphonal calling), subjects exhibited cFos expression in each of the above areas, as well as increased expression in perirhinal cortex. Overall, these results suggest that various cortical areas outside primary auditory cortex are involved in primate vocal communication. These findings pave the way for further physiological studies of the neural basis of primate vocal communication. PMID:21179582

  15. Historical evolution of the frontal lobe syndrome.

    PubMed

    Krudop, Welmoed A; Pijnenburg, Yolande A L

    2015-01-01

    The function of the frontal lobes and the related frontal lobe syndrome have not been described in detail until relatively late in history. Slowly, the combination of knowledge from animal models, the detailed examination of symptoms after traumatic frontal lobe injuries, and the rise and fall of psychosurgery has led to increasing insight into frontal lobe function. The frontosubcortical circuits have been described and increasingly related to clinical syndromes, confirmed by the latest developments in functional connectivity networks. PMID:25997476

  16. The Role of the Orbitofrontal Cortex in Human Discrimination Learning

    ERIC Educational Resources Information Center

    Chase, Henry W.; Clark, Luke; Myers, Catherine E.; Gluck, Mark A.; Sahakian, Barbara J.; Bullmore, Edward T.; Robbins, Trevor W.

    2008-01-01

    Several lines of evidence implicate the prefrontal cortex in learning but there is little evidence from studies of human lesion patients to demonstrate the critical role of this structure. To this end, we tested patients with lesions of the frontal lobe (n = 36) and healthy controls (n = 35) on two learning tasks: the weather prediction task…

  17. Prefrontal Cortex Contributions to Episodic Retrieval Monitoring and Evaluation

    ERIC Educational Resources Information Center

    Cruse, Damian; Wilding, Edward L.

    2009-01-01

    Although the prefrontal cortex (PFC) plays roles in episodic memory judgments, the specific processes it supports are not understood fully. Event-related potential (ERP) studies of episodic retrieval have revealed an electrophysiological modulation--the right-frontal ERP old/new effect--which is thought to reflect activity in PFC. The functional…

  18. Action selection and action value in frontal-striatal circuits

    PubMed Central

    Seo, Moonsang; Lee, Eunjeong; Averbeck, Bruno B.

    2012-01-01

    Summary The role that frontal-striatal circuits play in normal behavior remains unclear. Two of the leading hypotheses suggest that these circuits are important for action selection or reinforcement learning. To examine these hypotheses we carried out an experiment in which monkeys had to select actions in two different task conditions. In the first (random) condition actions were selected on the basis of perceptual inference. In the second (fixed) condition the animals used reinforcement from previous trials to select actions. Examination of neural activity showed that the representation of the selected action was stronger in lateral prefrontal cortex (lPFC), and occurred earlier in the lPFC than it did in the dorsal striatum (dSTR). In contrast to this, the representation of action values, in both the random and fixed conditions was stronger in the dSTR. Thus, the dSTR contains an enriched representation of action value, but it followed frontal cortex in action selection. PMID:22681697

  19. Frontal photopolymerization for microfluidic applications.

    PubMed

    Cabral, João T; Hudson, Steven D; Harrison, Christopher; Douglas, Jack F

    2004-11-01

    Frontal photopolymerization (FPP) offers numerous advantages for the rapid prototyping of microfluidic devices. Quantitative utilization of this method, however, requires a control of the vertical dimensions of the patterned resist material. To address this fundamental problem, we study the ultraviolet (UV) photopolymerization of a series of multifunctional thiolene resists through a combination of experiments and analytical modeling of the polymerization fronts. We describe this nonlinear spatio-temporal growth process in terms of a "minimal" model involving an order parameter phi(x, t) characterizing the extent of monomer-to-polymer conversion, the optical attenuation T(x, t), and the solid front position h(t). The latter exhibits an induction time (or equivalent critical UV dose) characterizing the onset of frontal propagation. We also observe a novel transition between two logarithmic rates of growth, determined by the Beer-Lambert attenuation constants mu(0) and mu(infinity) of the monomer and fully polymerized material, respectively. The measured frontal kinetics and optical transmission of the thiolene resist materials are consistent with our photopolymerization model, exhibiting both "photodarkening" and "photoinvariant" polymerization. This is apparently the first observation of photodarkening reported in FPP. On the basis of these results, multilevel fluidic devices with controlled height are readily fabricated with modulated illumination. A representative two-level microfluidic device, incorporating a chaotic mixer, a T junction, and a series of controlled flow constrictions, illustrates the practical versatility of this fabrication method. PMID:15518489

  20. Frontal and rostral anterior cingulate (rACC) theta EEG in depression: implications for treatment outcome?

    PubMed

    Arns, Martijn; Etkin, Amit; Hegerl, Ulrich; Williams, Leanne M; DeBattista, Charles; Palmer, Donna M; Fitzgerald, Paul B; Harris, Anthony; deBeuss, Roger; Gordon, Evian

    2015-08-01

    In major depressive disorder (MDD), elevated theta current density in the rostral anterior cingulate (rACC), as estimated by source localization of scalp-recorded electroencenphalogram (EEG), has been associated with response to antidepressant treatments, whereas elevated frontal theta has been linked to non-response. This study used source localization to attempt to integrate these apparently opposite results and test, whether antidepressant response is associated with elevated rACC theta and non-response with elevated frontal theta and whether theta activity is a differential predictor of response to different types of commonly used antidepressants. In the international Study to Predict Optimized Treatment in Depression (iSPOT-D), a multi-center, international, randomized, prospective practical trial, 1008 MDD participants were randomized to escitalopram, sertraline or venlafaxine-XR. The study also recruited 336 healthy controls. Treatment response and remission were established after eight weeks using the 17-item Hamilton Rating Scale for Depression (HRSD17). The resting-state EEG was assessed at baseline with eyes closed and source localization (eLORETA) was employed to extract theta from the rACC and frontal cortex. Patients with MDD had elevated theta in both frontal cortex and rACC, with small effect sizes. High frontal and rACC theta were associated with treatment non-response, but not with non-remission, and this effect was most pronounced in a subgroup with previous treatment failures. Low theta in frontal cortex and rACC are found in responders to antidepressant treatments with a small effect size. Future studies should investigate in more detail the role of previous treatment (failure) in the association between theta and treatment outcome. PMID:25936227

  1. Dual streams of auditory afferents target multiple domains in the primate prefrontal cortex

    PubMed Central

    Romanski, L. M.; Tian, B.; Fritz, J.; Mishkin, M.; Goldman-Rakic, P. S.; Rauschecker, J. P.

    2009-01-01

    ‘What’ and ‘where’ visual streams define ventrolateral object and dorsolateral spatial processing domains in the prefrontal cortex of nonhuman primates. We looked for similar streams for auditory–prefrontal connections in rhesus macaques by combining microelectrode recording with anatomical tract-tracing. Injection of multiple tracers into physiologically mapped regions AL, ML and CL of the auditory belt cortex revealed that anterior belt cortex was reciprocally connected with the frontal pole (area 10), rostral principal sulcus (area 46) and ventral prefrontal regions (areas 12 and 45), whereas the caudal belt was mainly connected with the caudal principal sulcus (area 46) and frontal eye fields (area 8a). Thus separate auditory streams originate in caudal and rostral auditory cortex and target spatial and non-spatial domains of the frontal lobe, respectively. PMID:10570492

  2. Estimating frontal and parietal involvement in cognitive estimation: a study of focal neurodegenerative diseases

    PubMed Central

    Bisbing, Teagan A.; Olm, Christopher A.; McMillan, Corey T.; Rascovsky, Katya; Baehr, Laura; Ternes, Kylie; Irwin, David J.; Clark, Robin; Grossman, Murray

    2015-01-01

    We often estimate an unknown value based on available relevant information, a process known as cognitive estimation. In this study, we assess the cognitive and neuroanatomic basis for quantitative estimation by examining deficits in patients with focal neurodegenerative disease in frontal and parietal cortex. Executive function and number knowledge are key components in cognitive estimation. Prefrontal cortex has been implicated in multilevel reasoning and planning processes, and parietal cortex has been associated with number knowledge required for such estimations. We administered the Biber cognitive estimation test (BCET) to assess cognitive estimation in 22 patients with prefrontal disease due to behavioral variant frontotemporal dementia (bvFTD), to 17 patients with parietal disease due to corticobasal syndrome (CBS) or posterior cortical atrophy (PCA) and 11 patients with mild cognitive impairment (MCI). Both bvFTD and CBS/PCA patients had significantly more difficulty with cognitive estimation than controls. MCI were not impaired on BCET relative to controls. Regression analyses related BCET performance to gray matter atrophy in right lateral prefrontal and orbital frontal cortices in bvFTD, and to atrophy in right inferior parietal cortex, right insula, and fusiform cortices in CBS/PCA. These results are consistent with the hypothesis that a frontal-parietal network plays a crucial role in cognitive estimation. PMID:26089786

  3. The effects of frontal lobe lesions on goal achievement in the water jug task.

    PubMed

    Colvin, M K; Dunbar, K; Grafman, J

    2001-11-15

    Patients with prefrontal cortex lesions are impaired on a variety of planning and problem-solving tasks. We examined the problem-solving performance of 27 patients with focal frontal lobe damage on the Water Jug task. The Water Jug task has never been used to assess problem-solving ability in neurologically impaired patients nor in functional neuroimaging studies, despite sharing structural similarities with other tasks sensitive to prefrontal cortex function, including the Tower of Hanoi, Tower of London, and Wisconsin Card Sorting Task (WCST). Our results demonstrate that the Water Jug task invokes a unique combination of problem-solving and planning strategies, allowing a more precise identification of frontal lobe lesion patients' cognitive deficits. All participants (patients and matched controls) appear to be utilizing a hill-climbing strategy that does not require sophisticated planning; however, frontal lobe lesion patients (FLLs) struggled to make required "counterintuitive moves" not predicted by this strategy and found within both solution paths. Left and bilateral FLLs were more impaired than right FLLs. Analysis of the left hemisphere brain regions encompassed by the lesions of these patients found that poor performance was linked to left dorsolateral prefrontal cortex damage. We propose that patients with left dorsolateral prefrontal cortex lesions have difficulty making a decision requiring the conceptual comparison of nonverbal stimuli, manipulation of select representations of potential solutions, and are unable to appropriately inhibit a response in keeping with the final goal. PMID:11784450

  4. Fracture of the frontal sinus in children.

    PubMed

    Weber, S C; Cohn, A M

    1977-04-01

    Two juvenile patients, ages 5 and 8, had traumatic fractures of the frontal sinus that included involvement of the nasal-frontal ducts and posterior tables. Principles of management are discussed and the techniques for the operative procedures described. While rare in occurrence in children, it is felt that traumatic involvement of the nasal-frontal ducts or posterior tables of the frontal sinus requires an osteoplastic flap--fat obliteration of the frontal sinus cavity in order to preclude subsequent mucocele development or mucosal ingrowth into the anterior fossa. PMID:849204

  5. [Frontal osteoplasty technique. Report of a case of giant frontal osteoma].

    PubMed

    García Rodríguez, M R; Cabanas López, A; Fernández Domínguez, A; García Calleja, J M; García Rodríguez, J F

    1991-01-01

    We present the case of a patient with old frontal headache, who was admitted with frontal acute sinusitis symptoms at the emergency service. The radiology study shows a compatible image with frontal osteoma, which was extirpated as being asymptomatic, by frontal osteoplastic technique. The case is described and it is made a frontal osteoma review and the surgical technique used to do it. PMID:2036264

  6. Prestimulus frontal-parietal coherence predicts auditory detection performance in rats

    PubMed Central

    Herzog, Linnea; Salehi, Kia; Bohon, Kaitlin S.

    2014-01-01

    Electrophysiology in primates has implicated long-range neural coherence as a potential mechanism for enhancing sensory detection. To test whether local synchronization and long-range neural coherence support detection performance in rats, we recorded local field potentials (LFPs) in frontal and parietal cortex while rats performed an auditory detection task. We observed significantly elevated power at multiple low frequencies (<15 Hz) preceding the target beep when the animal failed to respond to the signal (misses), in both frontal and parietal cortex. In terms of long-range coherence, we observed significantly more frontal-parietal coherence in the beta band (15–30 Hz) before the signal on misses compared with hits. This effect persisted after regressing away linear trends in the coherence values during a session, showing that the excess frontal-parietal beta coherence prior to misses cannot be explained by slow motivational changes during a session. In addition, a trend toward higher low-frequency (<15 Hz) coherence prior to miss trials compared with hits became highly significant when we rereferenced the LFPs to the mean voltage on each recording array, suggesting that the results are specific to our frontal and parietal areas. These results do not support a role for long-range frontal-parietal coherence or local synchronization in facilitating the detection of external stimuli. Rather, they extend to long-range frontal-parietal coherence previous findings that correlate local synchronization of low-frequency (<15 Hz) oscillations with inattention to external stimuli and synchronization of beta rhythms (15–30 Hz) with voluntary or involuntary prolongation of the current cognitive or motor state. PMID:24572093

  7. A genuine layer 4 in motor cortex with prototypical synaptic circuit connectivity.

    PubMed

    Yamawaki, Naoki; Borges, Katharine; Suter, Benjamin A; Harris, Kenneth D; Shepherd, Gordon M G

    2014-01-01

    The motor cortex (M1) is classically considered an agranular area, lacking a distinct layer 4 (L4). Here, we tested the idea that M1, despite lacking a cytoarchitecturally visible L4, nevertheless possesses its equivalent in the form of excitatory neurons with input-output circuits like those of the L4 neurons in sensory areas. Consistent with this idea, we found that neurons located in a thin laminar zone at the L3/5A border in the forelimb area of mouse M1 have multiple L4-like synaptic connections: excitatory input from thalamus, largely unidirectional excitatory outputs to L2/3 pyramidal neurons, and relatively weak long-range corticocortical inputs and outputs. M1-L4 neurons were electrophysiologically diverse but morphologically uniform, with pyramidal-type dendritic arbors and locally ramifying axons, including branches extending into L2/3. Our findings therefore identify pyramidal neurons in M1 with the expected prototypical circuit properties of excitatory L4 neurons, and question the traditional assumption that motor cortex lacks this layer. PMID:25525751

  8. Biomechanics of frontal skull fracture.

    PubMed

    Delye, Hans; Verschueren, Peter; Depreitere, Bart; Verpoest, Ignaas; Berckmans, Daniel; Vander Sloten, Jos; Van Der Perre, Georges; Goffin, Jan

    2007-10-01

    The purpose of the present study was to investigate whether an energy failure level applies to the skull fracture mechanics in unembalmed post-mortem human heads under dynamic frontal loading conditions. A double-pendulum model was used to conduct frontal impact tests on specimens from 18 unembalmed post-mortem human subjects. The specimens were isolated at the occipital condyle level, and pre-test computed tomography images were obtained. The specimens were rigidly attached to an aluminum pendulum in an upside down position and obtained a single degree of freedom, allowing motion in the plane of impact. A steel pendulum delivered the impact and was fitted with a flat-surfaced, cylindrical aluminum impactor, which distributed the load to a force sensor. The relative displacement between the two pendulums was used as a measure for the deformation of the specimen in the plane of impact. Three impact velocity conditions were created: low (3.60+/-0.23 m/sec), intermediate (5.21+/-0.04 m/sec), and high (6.95+/-0.04 m/sec) velocity. Computed tomography and dissection techniques were used to detect pathology. If no fracture was detected, repeated tests on the same specimen were performed with higher impact energy until fracture occurred. Peak force, displacement and energy variables were used to describe the biomechanics. Our data suggests the existence of an energy failure level in the range of 22-24 J for dynamic frontal loading of an intact unembalmed head, allowed to move with one degree of freedom. Further experiments, however, are necessary to confirm that this is a definitive energy criterion for skull fracture following impact. PMID:17970621

  9. Slowly progressive anarthria with late anterior opercular syndrome: a variant form of frontal cortical atrophy syndromes.

    PubMed

    Broussolle, E; Bakchine, S; Tommasi, M; Laurent, B; Bazin, B; Cinotti, L; Cohen, L; Chazot, G

    1996-12-01

    We describe eight patients with slowly progressive speech production deficit combining speech apraxia, dysarthria, dysprosody and orofacial apraxia, and initially no other deficit in other language and non-language neuropsychological domains. Long-term follow-up (6-10 years) in 4 cases showed an evolution to muteness, bilateral suprabulbar paresis with automatic-voluntary dissociation and frontal lobe cognitive slowing without generalised intellectual deterioration. Most disabled patients presented with an anterior opercular syndrome (Foix-Chavany-Marie syndrome), and pyramidal or extrapyramidal signs. CT and MRI findings disclosed asymmetric (left > right) progressive cortical atrophy of the frontal lobes predominating in the posterior inferior frontal region, notably the operculum. SPECT and PET revealed a decreased cerebral blood flow and metabolism, prominent in the left posterior-inferior frontal gyrus and premotor cortex, extending bilaterally in the most advanced cases. Pathological study of two cases showed non-specific neuronal loss, gliosis, and spongiosis of superficial cortical layers, mainly confined to the frontal lobes, with no significant abnormalities in the basal ganglia, thalamus, cerebellum, brain stem (except severe neuronal loss in the substantia nigra in one case), and spinal cord. We propose to call this peculiar syndrome Slowly Progressive Anarthria (SPA), based on its specific clinical presentation, and its metabolic and pathological correlates. SPA represents another clinical expression of focal cortical degeneration syndromes, that may overlap with other similar syndromes, specially primary progressive aphasia and the various frontal lobe dementias. PMID:8994103

  10. The human cerebral cortex flattens during adolescence.

    PubMed

    Alemán-Gómez, Yasser; Janssen, Joost; Schnack, Hugo; Balaban, Evan; Pina-Camacho, Laura; Alfaro-Almagro, Fidel; Castro-Fornieles, Josefina; Otero, Soraya; Baeza, Immaculada; Moreno, Dolores; Bargalló, Nuria; Parellada, Mara; Arango, Celso; Desco, Manuel

    2013-09-18

    The human cerebral cortex appears to shrink during adolescence. To delineate the dynamic morphological changes involved in this process, 52 healthy male and female adolescents (11-17 years old) were neuroimaged twice using magnetic resonance imaging, approximately 2 years apart. Using a novel morphometric analysis procedure combining the FreeSurfer and BrainVisa image software suites, we quantified global and lobar change in cortical thickness, outer surface area, the gyrification index, the average Euclidean distance between opposing sides of the white matter surface (gyral white matter thickness), the convex ("exposed") part of the outer cortical surface (hull surface area), sulcal length, depth, and width. We found that the cortical surface flattens during adolescence. Flattening was strongest in the frontal and occipital cortices, in which significant sulcal widening and decreased sulcal depth co-occurred. Globally, sulcal widening was associated with cortical thinning and, for the frontal cortex, with loss of surface area. For the other cortical lobes, thinning was related to gyral white matter expansion. The overall flattening of the macrostructural three-dimensional architecture of the human cortex during adolescence thus involves changes in gray matter and effects of the maturation of white matter. PMID:24048830

  11. Increase in c-Fos and Arc protein in retrosplenial cortex after memory-improving lateral hypothalamic electrical stimulation treatment.

    PubMed

    Kádár, Elisabeth; Vico-Varela, Eva; Aldavert-Vera, Laura; Huguet, Gemma; Morgado-Bernal, Ignacio; Segura-Torres, Pilar

    2016-02-01

    Post-training Intracranial self-stimulation (ICSS) of the lateral hypothalamus (LH), a kind of rewarding deep-brain stimulation, potentiates learning and memory and increases c-Fos protein expression in specific memory-related brain regions. In a previous study, Aldavert-Vera et al. (2013) reported that post-acquisition LH-ICSS improved 48 h retention of a delay two-way active avoidance conditioning (TWAA) and induced c-Fos expression increase in CA3 at 90 min after administration. Nevertheless, this c-Fos induction was only observed after the acquisition session and not after the retention test at 48 h, when the ICSS improving effect was observed on memory. This current study aims to examine the hypothesis that post-training ICSS treatment may stimulate c-Fos expression at the time of the TWAA retention test in retrosplenial cortex (RSC), a hippocampus-related brain region more closely related with long-lasting memory storage. Effects of ICSS on Arc protein, a marker of memory-associated synaptic plasticity, were also measured by immunohistochemistry in granular and agranular RSC. The most innovative results are that the ICSS treatment potentiates the c-Fos induction across TWAA conditions (no conditioning, acquisition and retention), specifically in layer V of the granular RSC, along with increases of Arc protein levels in the granular but not in agranular areas of RSC ipsilaterally few hours after ICSS. This leads us to suggest that plasticity-related protein activation in the granular RSC could be involved in the positive modulatory effects of ICSS on TWAA memory consolidation, opening a new approach for future research in ICSS memory facilitation. PMID:26774022

  12. When anger leads to aggression: induction of relative left frontal cortical activity with transcranial direct current stimulation increases the anger–aggression relationship

    PubMed Central

    Hortensius, Ruud; Schutter, Dennis J. L. G.

    2012-01-01

    The relationship between anger and aggression is imperfect. Based on work on the neuroscience of anger, we predicted that anger associated with greater relative left frontal cortical activation would be more likely to result in aggression. To test this hypothesis, we combined transcranial direct current stimulation (tDCS) over the frontal cortex with interpersonal provocation. Participants received insulting feedback after 15 min of tDCS and were able to aggress by administering noise blasts to the insulting participant. Individuals who received tDCS to increase relative left frontal cortical activity behaved more aggressively when they were angry. No relation between anger and aggression was observed in the increase relative right frontal cortical activity or sham condition. These results concur with the motivational direction model of frontal asymmetry, in which left frontal activity is associated with anger. We propose that anger with approach motivational tendencies is more likely to result in aggression. PMID:21421731

  13. When anger leads to aggression: induction of relative left frontal cortical activity with transcranial direct current stimulation increases the anger-aggression relationship.

    PubMed

    Hortensius, Ruud; Schutter, Dennis J L G; Harmon-Jones, Eddie

    2012-03-01

    The relationship between anger and aggression is imperfect. Based on work on the neuroscience of anger, we predicted that anger associated with greater relative left frontal cortical activation would be more likely to result in aggression. To test this hypothesis, we combined transcranial direct current stimulation (tDCS) over the frontal cortex with interpersonal provocation. Participants received insulting feedback after 15 min of tDCS and were able to aggress by administering noise blasts to the insulting participant. Individuals who received tDCS to increase relative left frontal cortical activity behaved more aggressively when they were angry. No relation between anger and aggression was observed in the increase relative right frontal cortical activity or sham condition. These results concur with the motivational direction model of frontal asymmetry, in which left frontal activity is associated with anger. We propose that anger with approach motivational tendencies is more likely to result in aggression. PMID:21421731

  14. Behavioral and hormonal reactivity to threat: Effects of selective amygdala, hippocampal or orbital frontal lesions in monkeys

    PubMed Central

    Machado, Christopher J.; Bachevalier, Jocelyne

    2008-01-01

    Summary We compared the effects of bilateral amygdala, hippocampal or orbital frontal cortex lesions on emotional and hormonal reactivity in rhesus monkeys (Macaca mulatta). Experiment 1 measured behavioral reactivity to an unfamiliar human intruder before and after surgery. Animals with amygdala lesions demonstrated decreases in one passive defensive behavior (freezing), whereas animals with hippocampal lesions showed decreases in a more stimulus-directed defensive behavior (tooth grinding). Orbital frontal cortex lesions also reduced these two defensive behaviors, as well as decreased cage-shaking dominance displays. Animals with amygdala, hippocampal or sham lesions also demonstrated increased tension-related behaviors after surgery, but those with orbital frontal lesions did not. Finally, all three lesions diminished the operated animals' ability to modulate tension-related behaviors depending on the magnitude of threat posed by the human intruder. Experiment 2 measured circulating levels of cortisol and testosterone when a subset of these same animals were at rest and following physical restraint, temporary isolation, exposure to threatening objects and social interactions with an unfamiliar conspecific. None of the lesions impacted on testosterone levels in any condition. Amygdala or orbital frontal lesions blunted cortisol reactivity during isolation from peers, but not during any other condition. Hippocampal lesions did not alter circulating levels of cortisol under any conditions. These results indicate that the amygdala, hippocampus and orbital frontal cortex play distinct, yet complimentary roles in coordinating emotional and hormonal reactivity to threat. PMID:18650022

  15. Dissociation in prefrontal cortex of affective and attentional shifts.

    PubMed

    Dias, R; Robbins, T W; Roberts, A C

    1996-03-01

    The prefrontal cortex is implicated in such human characteristics as volition, planning, abstract reasoning and affect. Frontal-lobe damage can cause disinhibition such that the behaviour of a subject is guided by previously acquired responses that are inappropriate to the current situation. Here we demonstrate that disinhibition, or a loss of inhibitory control, can be selective for particular cognitive functions and that different regions of the prefrontal cortex provide inhibitory control in different aspects of cognitive processing. Thus, whereas damage to the lateral prefrontal cortex (Brodmann's area 9) in monkeys causes a loss of inhibitory control in attentional selection, damage to the orbito-frontal cortex in monkeys causes a loss of inhibitory control in 'affective' processing, thereby impairing the ability to alter behaviour in response to fluctuations in the emotional significance of stimuli. These findings not only support the view that the prefrontal cortex has multiple functions, but also provide evidence for the distribution of different cognitive functions within specific regions of prefrontal cortex. PMID:8598908

  16. Anatomic Considerations in Frontal Sinus Surgery.

    PubMed

    Folbe, Adam J; Svider, Peter F; Eloy, Jean Anderson

    2016-08-01

    Comprehension of the complex anatomic variants comprising the frontal sinus outflow tract is essential for successful surgical intervention. Deviation from sound technique increases the potential for a variety of deleterious sequelae, including recurrent disease as well as catastrophic intracranial and orbital injury. Furthermore, incomplete removal of elements occluding the frontal recess can result in severe stenosis that can increase the difficulty of further interventions. This review covers anatomic considerations that should be kept in mind when performing frontal sinus surgery. PMID:27329978

  17. NADPH-diaphorase activity and neurovascular coupling in the rat cerebral cortex.

    PubMed

    Vlasenko, O V; Maisky, V A; Maznychenko, A V; Pilyavskii, A I

    2008-01-01

    The distribution of NADPH-diaphorase-reactive (NADPH-dr) neurons and neuronal processes in the cerebral cortex and basal forebrain and their association with parenchymal vessels were studied in normal adult rats using NADPH-d histochemical protocol. The intensely stained cortical interneurons and reactive subcortically originating afferents, and stained microvessels were examined through a light microscope at law (x250) and high (x630) magnifications. NADPH-dr interneurons were concentrated in layers 2-6 of the M1 and M2 areas. However, clear predominance in their concentration (14 +/- 0.8 P < 0.05 per section) was found in layer 6. A mean number of labeled neurons in auditory (AuV), granular and agranular (GI, AIP) areas of the insular cortex was calculated to reach 12.3 +/- 0.7, 18.5 +/- 1.0 and 23.3 +/- 1.7 units per section, respectively (P < 0.05). The distinct apposition of labelled neurons to intracortical vessels was found in the M1, M2. The order of frequency of neurovascular coupling in different zones of the cerebral cortex was as following sequence: AuV (31.2%, n = 1040) > GI (18.0%, n = 640) > S1 (13.3%, n = 720) > M1 (6.3%, n = 1360). A large number of structural associations between labeled cells and vessels in the temporal and insular cortex indicate that NADPH-d-reactive interneurons can contribute to regulation of the cerebral regional blood flow in these areas. PMID:18416183

  18. Overview of Frontal Sinus Pathology and Management.

    PubMed

    Vázquez, Alejandro; Baredes, Soly; Setzen, Michael; Eloy, Jean Anderson

    2016-08-01

    The frontal sinus is the most complex of all paranasal sinuses. Given its proximity to the cranial vault and orbit, frontal sinus pathology can progress to involve these structures and lead to significant morbidity, or even mortality. Surgical management of the frontal sinus is technically challenging. Various open and endoscopic surgical techniques are available to the otolaryngologist. This article presents an overview of the major disease entities that affect the frontal sinus, with a special emphasis on treatment principles and surgical management. PMID:27329984

  19. Frontal Midline Theta Reflects Anxiety and Cognitive Control: Meta-Analytic Evidence

    PubMed Central

    Cavanagh, James F.; Shackman, Alexander J.

    2014-01-01

    Evidence from imaging and anatomical studies suggests that the midcingulate cortex (MCC) is a dynamic hub lying at the interface of affect and cognition. In particular, this neural system appears to integrate information about conflict and punishment in order to optimize behavior in the face of action-outcome uncertainty. In a series of meta-analyses, we show how recent human electrophysiological research provides compelling evidence that frontal-midline theta signals reflecting MCC activity are moderated by anxiety and predict adaptive behavioral adjustments. These findings underscore the importance of frontal theta activity to a broad spectrum of control operations. We argue that frontal-midline theta provides a neurophysiologically plausible mechanism for optimally adjusting behavior to uncertainty, a hallmark of situations that elicit anxiety and demand cognitive control. These observations compel a new perspective on the mechanisms guiding motivated learning and behavior and provide a framework for understanding the role of the MCC in temperament and psychopathology. PMID:24787485

  20. Frontal midline theta reflects anxiety and cognitive control: meta-analytic evidence.

    PubMed

    Cavanagh, James F; Shackman, Alexander J

    2015-01-01

    Evidence from imaging and anatomical studies suggests that the midcingulate cortex (MCC) is a dynamic hub lying at the interface of affect and cognition. In particular, this neural system appears to integrate information about conflict and punishment in order to optimize behavior in the face of action-outcome uncertainty. In a series of meta-analyses, we show how recent human electrophysiological research provides compelling evidence that frontal-midline theta signals reflecting MCC activity are moderated by anxiety and predict adaptive behavioral adjustments. These findings underscore the importance of frontal theta activity to a broad spectrum of control operations. We argue that frontal-midline theta provides a neurophysiologically plausible mechanism for optimally adjusting behavior to uncertainty, a hallmark of situations that elicit anxiety and demand cognitive control. These observations compel a new perspective on the mechanisms guiding motivated learning and behavior and provide a framework for understanding the role of the MCC in temperament and psychopathology. PMID:24787485

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

    PubMed Central

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

    2006-01-01

    Motivationally significant agendas guide perception, thought and behaviour, helping one to define a ‘self’ and to regulate interactions with the environment. To investigate neural correlates of thinking about such agendas, we asked participants to think about their hopes and aspirations (promotion focus) or their duties and obligations (prevention focus) during functional magnetic resonance imaging and compared these self-reflection conditions with a distraction condition in which participants thought about non-self-relevant items. Self-reflection resulted in greater activity than distraction in dorsomedial frontal/anterior cingulate cortex and posterior cingulate cortex/precuneus, consistent with previous findings of activity in these areas during self-relevant thought. For additional medial areas, we report new evidence of a double dissociation of function between medial prefrontal/anterior cingulate cortex, which showed relatively greater activity to thinking about hopes and aspirations, and posterior cingulate cortex/precuneus, which showed relatively greater activity to thinking about duties and obligations. One possibility is that activity in medial prefrontal cortex is associated with instrumental or agentic self-reflection, whereas posterior medial cortex is associated with experiential self-reflection. Another, not necessarily mutually exclusive, possibility is that medial prefrontal cortex is associated with a more inward-directed focus, while posterior cingulate is associated with a more outward-directed, social or contextual focus. PMID:18574518

  2. Numerical studies of frontal dynamics

    NASA Technical Reports Server (NTRS)

    Keyser, Daniel

    1986-01-01

    Efforts concentrated on the development of a two dimensional primitive equation (PE) model of frontogenesis that simultaneously incorporates the frontagenetical mechanisms of confluence and horizontal shear. Applying this model to study the effects of upper level frontogenesis, it appeared to be dominated by tilting effects associated with cross front variation of vertical motion, in which subsidence is maximized within and to the warm side of the frontal zone. Results suggest that aspects characteristic of three-dimensional baroclinic waves may be abstracted to a significant extent in a two dimensional framework. They also show that upper-level frontogenesis and tropopause folding can occur in the absence of three-dimensional curvature effects, commonly believed to be necessary for realistic upper-level frontogenesis. An implication of the dominant tilting effects is that they may have to be adequately resolved by numerical weather prediction models, thus requiring better horizontal and vertical resolution.

  3. Frontal preparatory neural oscillations associated with cognitive control: A developmental study comparing young adults and adolescents.

    PubMed

    Hwang, Kai; Ghuman, Avniel S; Manoach, Dara S; Jones, Stephanie R; Luna, Beatriz

    2016-08-01

    Functional magnetic resonance imaging (fMRI) studies suggest that age-related changes in the frontal cortex may underlie developmental improvements in cognitive control. In the present study we used magnetoencephalography (MEG) to identify frontal oscillatory neurodynamics that support age-related improvements in cognitive control during adolescence. We characterized the differences in neural oscillations in adolescents and adults during the preparation to suppress a prepotent saccade (antisaccade trials-AS) compared to preparing to generate a more automatic saccade (prosaccade trials-PS). We found that for adults, AS were associated with increased beta-band (16-38Hz) power in the dorsal lateral prefrontal cortex (DLPFC), enhanced alpha- to low beta-band (10-18Hz) power in the frontal eye field (FEF) that predicted performance, and increased cross-frequency alpha-beta (10-26Hz) amplitude coupling between the DLPFC and the FEF. Developmental comparisons between adults and adolescents revealed similar engagement of DLPFC beta-band power but weaker FEF alpha-band power, and lower cross-frequency coupling between the DLPFC and the FEF in adolescents. These results suggest that lateral prefrontal neural activity associated with cognitive control is adult-like by adolescence; the development of cognitive control from adolescence to adulthood is instead associated with increases in frontal connectivity and strengthening of inhibition signaling for suppressing task-incompatible processes. PMID:27173759

  4. Medial Prefrontal Cortex Plays a Critical and Selective Role in "Feeling of Knowing" Meta-Memory Judgments

    ERIC Educational Resources Information Center

    Modirrousta, Mandana; Fellows, Lesley K.

    2008-01-01

    The frontal lobes are thought to play a role in the monitoring of memory performance, or "meta-memory," but the specific circuits involved have yet to be definitively established. Medial prefrontal cortex in general and the anterior cingulate cortex in particular, have been implicated in other forms of monitoring, such as error and conflict…

  5. Frontal and Parietal Cortices Show Different Spatiotemporal Dynamics across Problem-solving Stages.

    PubMed

    Tschentscher, Nadja; Hauk, Olaf

    2016-08-01

    Arithmetic problem-solving can be conceptualized as a multistage process ranging from task encoding over rule and strategy selection to step-wise task execution. Previous fMRI research suggested a frontal-parietal network involved in the execution of complex numerical and nonnumerical tasks, but evidence is lacking on the particular contributions of frontal and parietal cortices across time. In an arithmetic task paradigm, we evaluated individual participants' "retrieval" and "multistep procedural" strategies on a trial-by-trial basis and contrasted those in time-resolved analyses using combined EEG and MEG. Retrieval strategies relied on direct retrieval of arithmetic facts (e.g., 2 + 3 = 5). Procedural strategies required multiple solution steps (e.g., 12 + 23 = 12 + 20 + 3 or 23 + 10 + 2). Evoked source analyses revealed independent activation dynamics within the first second of problem-solving in brain areas previously described as one network, such as the frontal-parietal cognitive control network: The right frontal cortex showed earliest effects of strategy selection for multistep procedural strategies around 300 msec, before parietal cortex activated around 700 msec. In time-frequency source power analyses, memory retrieval and multistep procedural strategies were differentially reflected in theta, alpha, and beta frequencies: Stronger beta and alpha desynchronizations emerged for procedural strategies in right frontal, parietal, and temporal regions as function of executive demands. Arithmetic fact retrieval was reflected in right prefrontal increases in theta power. Our results demonstrate differential brain dynamics within frontal-parietal networks across the time course of a problem-solving process, and analyses of different frequency bands allowed us to disentangle cortical regions supporting the underlying memory and executive functions. PMID:27027542

  6. Putting the brakes on inhibitory models of frontal lobe function

    PubMed Central

    Hampshire, Adam

    2015-01-01

    There has been much recent debate regarding the neural basis of motor response inhibition. An influential hypothesis from the last decade proposes that a module within the right inferior frontal cortex (RIFC) of the human brain is dedicated to supporting response inhibition. However, there is growing evidence to support the alternative view that response inhibition is just one prominent example of the many cognitive control processes that are supported by the same set of ‘domain general’ functional networks. Here, I test directly between the modular and network accounts of motor response inhibition by applying a combination of data-driven, event-related and functional connectivity analyses to fMRI data from a variety of attention and inhibition tasks. The results demonstrate that there is no inhibitory module within the RIFC. Instead, response inhibition recruits a functionally heterogeneous ensemble of RIFC networks, which can be dissociated from each other in the context of other task demands. PMID:25818684

  7. Frontal neurons modulate memory retrieval across widely varying temporal scales.

    PubMed

    Zhang, Wen-Hua; Williams, Ziv M

    2015-06-01

    Once a memory has formed, it is thought to undergo a gradual transition within the brain from short- to long-term storage. This putative process, however, also poses a unique problem to the memory system in that the same learned items must also be retrieved across broadly varying time scales. Here, we find that neurons in the ventrolateral prefrontal cortex (VLPFC) of monkeys, an area interconnected with both temporal and frontal associative neocortical regions, signaled the need to alter between retrieval of memories formed at different times. These signals were most closely related to the time interval between initial learning and later retrieval, and did not correlate with task switch demands, novelty, or behavioral response. Consistent with these physiological findings, focal inactivation of the VLPFC led to a marked degradation in retrieval performance. These findings suggest that the VLPFC plays a necessary regulatory role in retrieving memories over different temporal scales. PMID:25979992

  8. Transient global amnesia and left frontal haemorrhage.

    PubMed Central

    Jacome, D. E.; Yanez, G. F.

    1988-01-01

    A patient developed spontaneous, acute, dominant frontal lobe haemorrhage neighbouring on a zone of pre-existing post-traumatic encephalomalacia manifesting clinically as transient global amnesia. Amnesia can be secondary to disease of the frontal lobe, affecting pathways interconnecting the basal forebrain and hippocampus of the temporal lobe. Images Figure 1 PMID:3174526

  9. The surgery of frontal sinus infection.

    PubMed

    Du Preez, S F; Collard, W M; Sellars, S L

    1975-11-01

    A clinical and surgical review of 37 patients treated for acute and chronic frontal sinusitis at Groote Schuur Hospital during the 6-year period 1967-1972, is presented. The mode of clinical presentation of this disease and its complications are discussed, and the surgical management of frontal sinus disease as practised at this hospital is described. PMID:1198214

  10. Co-activation based parcellation of the human frontal pole.

    PubMed

    Ray, K L; Zald, D H; Bludau, S; Riedel, M C; Bzdok, D; Yanes, J; Falcone, K E; Amunts, K; Fox, P T; Eickhoff, S B; Laird, A R

    2015-12-01

    Historically, the human frontal pole (FP) has been considered as a single architectonic area. Brodmann's area 10 is located in the frontal lobe with known contributions in the execution of various higher order cognitive processes. However, recent cytoarchitectural studies of the FP in humans have shown that this portion of cortex contains two distinct cytoarchitectonic regions. Since architectonic differences are accompanied by differential connectivity and functions, the frontal pole qualifies as a candidate region for exploratory parcellation into functionally discrete sub-regions. We investigated whether this functional heterogeneity is reflected in distinct segregations within cytoarchitectonically defined FP-areas using meta-analytic co-activation based parcellation (CBP). The CBP method examined the co-activation patterns of all voxels within the FP as reported in functional neuroimaging studies archived in the BrainMap database. Voxels within the FP were subsequently clustered into sub-regions based on the similarity of their respective meta-analytically derived co-activation maps. Performing this CBP analysis on the FP via k-means clustering produced a distinct 3-cluster parcellation for each hemisphere corresponding to previously identified cytoarchitectural differences. Post-hoc functional characterization of clusters via BrainMap metadata revealed that lateral regions of the FP mapped to memory and emotion domains, while the dorso- and ventromedial clusters were associated broadly with emotion and social cognition processes. Furthermore, the dorsomedial regions contain an emphasis on theory of mind and affective related paradigms whereas ventromedial regions couple with reward tasks. Results from this study support previous segregations of the FP and provide meta-analytic contributions to the ongoing discussion of elucidating functional architecture within human FP. PMID:26254112

  11. Functional role of frontal alpha oscillations in creativity.

    PubMed

    Lustenberger, Caroline; Boyle, Michael R; Foulser, A Alban; Mellin, Juliann M; Fröhlich, Flavio

    2015-06-01

    Creativity, the ability to produce innovative ideas, is a key higher-order cognitive function that is poorly understood. At the level of macroscopic cortical network dynamics, recent electroencephalography (EEG) data suggests that cortical oscillations in the alpha frequency band (8-12 Hz) are correlated with creative thinking. However, whether alpha oscillations play a functional role in creativity has remained unknown. Here we show that creativity is increased by enhancing alpha power using 10 Hz transcranial alternating current stimulation (10 Hz-tACS) of the frontal cortex. In a study of 20 healthy participants with a randomized, balanced cross-over design, we found a significant improvement of 7.4% in the Creativity Index measured by the Torrance Test of Creative Thinking (TTCT), a comprehensive and most frequently used assay of creative potential and strengths. In a second similar study with 20 subjects, 40 Hz-tACS was used instead of 10 Hz-tACS to rule out a general "electrical stimulation" effect. No significant change in the Creativity Index was found for such frontal 40 Hz stimulation. Our results suggest that alpha activity in frontal brain areas is selectively involved in creativity; this enhancement represents the first demonstration of specific neuronal dynamics that drive creativity and can be modulated by non-invasive brain stimulation. Our findings agree with the model that alpha recruitment increases with internal processing demands and is involved in inhibitory top-down control, which is an important requirement for creative ideation. PMID:25913062

  12. Role of the left frontal aslant tract in stuttering: a brain stimulation and tractographic study.

    PubMed

    Kemerdere, Rahsan; de Champfleur, Nicolas Menjot; Deverdun, Jérémy; Cochereau, Jérôme; Moritz-Gasser, Sylvie; Herbet, Guillaume; Duffau, Hugues

    2016-01-01

    The neural correlates of stuttering are to date incompletely understood. Although the possible involvement of the basal ganglia, the cerebellum and certain parts of the cerebral cortex in this speech disorder has previously been reported, there are still not many studies investigating the role of white matter fibers in stuttering. Axonal stimulation during awake surgery provides a unique opportunity to study the functional role of structural connectivity. Here, our goal was to investigate the white matter tracts implicated in stuttering, by combining direct electrostimulation mapping and postoperative tractography imaging, with a special focus on the left frontal aslant tract. Eight patients with no preoperative stuttering underwent awake surgery for a left frontal low-grade glioma. Intraoperative cortical and axonal electrical mapping was used to interfere in speech processing and subsequently provoke stuttering. We further assessed the relationship between the subcortical sites leading to stuttering and the spatial course of the frontal aslant tract. All patients experienced intraoperative stuttering during axonal electrostimulation. On postsurgical tractographies, the subcortical distribution of stimulated sites matched the topographical position of the left frontal aslant tract. This white matter pathway was preserved during surgery, and no patients had postoperative stuttering. For the first time to our knowledge, by using direct axonal stimulation combined with postoperative tractography, we provide original data supporting a pivotal role of the left frontal aslant tract in stuttering. We propose that this speech disorder could be the result of a disconnection within a large-scale cortico-subcortical circuit subserving speech motor control. PMID:26559819

  13. Frontal Lobe Contusion in Mice Chronically Impairs Prefrontal-Dependent Behavior.

    PubMed

    Chou, Austin; Morganti, Josh M; Rosi, Susanna

    2016-01-01

    Traumatic brain injury (TBI) is a major cause of chronic disability in the world. Moderate to severe TBI often results in damage to the frontal lobe region and leads to cognitive, emotional, and social behavioral sequelae that negatively affect quality of life. More specifically, TBI patients often develop persistent deficits in social behavior, anxiety, and executive functions such as attention, mental flexibility, and task switching. These deficits are intrinsically associated with prefrontal cortex (PFC) functionality. Currently, there is a lack of analogous, behaviorally characterized TBI models for investigating frontal lobe injuries despite the prevalence of focal contusions to the frontal lobe in TBI patients. We used the controlled cortical impact (CCI) model in mice to generate a frontal lobe contusion and studied behavioral changes associated with PFC function. We found that unilateral frontal lobe contusion in mice produced long-term impairments to social recognition and reversal learning while having only a minor effect on anxiety and completely sparing rule shifting and hippocampal-dependent behavior. PMID:26964036

  14. Frontal Lobe Contusion in Mice Chronically Impairs Prefrontal-Dependent Behavior

    PubMed Central

    Rosi, Susanna

    2016-01-01

    Traumatic brain injury (TBI) is a major cause of chronic disability in the world. Moderate to severe TBI often results in damage to the frontal lobe region and leads to cognitive, emotional, and social behavioral sequelae that negatively affect quality of life. More specifically, TBI patients often develop persistent deficits in social behavior, anxiety, and executive functions such as attention, mental flexibility, and task switching. These deficits are intrinsically associated with prefrontal cortex (PFC) functionality. Currently, there is a lack of analogous, behaviorally characterized TBI models for investigating frontal lobe injuries despite the prevalence of focal contusions to the frontal lobe in TBI patients. We used the controlled cortical impact (CCI) model in mice to generate a frontal lobe contusion and studied behavioral changes associated with PFC function. We found that unilateral frontal lobe contusion in mice produced long-term impairments to social recognition and reversal learning while having only a minor effect on anxiety and completely sparing rule shifting and hippocampal-dependent behavior. PMID:26964036

  15. White matter lesions impair frontal lobe function regardless of their location

    PubMed Central

    Tullberg, M.; Fletcher, E.; DeCarli, C.; Mungas, D.; Reed, B.R.; Harvey, D.J.; Weiner, M.W.; Chui, H.C.; Jagust, W.J.

    2007-01-01

    Objective To analyze the effect of white matter lesions in different brain regions on regional cortical glucose metabolism, regional cortical atrophy, and cognitive function in a sample with a broad range of cerebrovascular disease and cognitive function. Methods Subjects (n = 78) were recruited for a study of subcortical ischemic vascular disease (SIVD) and Alzheimer disease (AD) contributions to dementia. A new method was developed to define volumes of interest from high-resolution three-dimensional T1-weighted MR images. Volumetric measures of MRI segmented white matter signal hyperintensities (WMH) in five different brain regions were related to regional PET glucose metabolism (rCMRglc) in cerebral cortex, MRI measures of regional cortical atrophy, and neuropsychological assessment of executive and memory function. Results WMH was significantly higher in the prefrontal region compared to the other brain regions. In all subjects, higher frontal and parietal WMH were associated with reduced frontal rCMRglc, whereas occipitotemporal WMH was only marginally associated with frontal rCMRglc. These associations were stronger and more widely distributed in nondemented subjects where reduced frontal rCMRglc was correlated with WMH for all regions measured. In contrast, there was no relationship between WMH in any brain region and rCMRglc in either parietal or occipitotemporal regions. WMHs in all brain regions were associated with low executive scores in nondemented subjects. Conclusions The frontal lobes are most severely affected by SIVD. WMHs are more abundant in the frontal region. Regardless of where in the brain these WMHs are located, they are associated with frontal hypometabolism and executive dysfunction. PMID:15277616

  16. Disruption of attention to novel events after frontal lobe injury in humans

    PubMed Central

    Daffner, K.; Mesulam, M; Holcomb, P.; Calvo, V.; Acar, D.; Chabrerie, A.; Kikinis, R.; Jolesz, F.; Rentz, D.; Scinto, L.

    2000-01-01

    OBJECTIVE—To investigate whether frontal lobe damage in humans disrupts the natural tendency to preferentially attend to novel visual events in the environment.
METHODS—Nine patients with chronic infarctions in the dorsolateral prefrontal cortex (DLPFC) and 23 matched normal controls participated in a study in which subjects viewed repetitive background stimuli, infrequent target stimuli, and novel visual stimuli (for example, fragmented or "impossible" objects). Subjects controlled viewing duration by a button press that led to the onset of the next stimulus. They also responded to targets by pressing a foot pedal. The amount of time spent looking at the different kinds of stimuli, and the target detection accuracy and speed served as dependent variables.
RESULTS—Overall, normal controls spent significantly more time than frontal lobe patients looking at novel stimuli. Analysis of responses across blocks showed that initially frontal lobe patients behaved like normal controls by directing more attention to novel than background stimuli. However, they quickly began to distribute their viewing time evenly between novel and background stimuli, a pattern that was strikingly different from normal controls. By contrast, there were no differences between frontal lobe patients and normal controls for viewing duration devoted to background and target stimuli, target detection accuracy, or reaction time to targets. Frontal lobe patients did not differ from normal controls in terms of age, education, estimated IQ, or mood, but were more apathetic as measured by self report and informants' judgments. Attenuated responses to novel stimuli significantly correlated with degree of apathy.
CONCLUSIONS—This study demonstrates that DLPFC injury selectively impairs the natural tendency to seek stimulation from novel and unusual stimuli. These data provide the first quantitative behavioural demonstration that the human frontal lobes play a critical part in directing and

  17. Bipolar Mood Tendency and Frontal Activation Using a Multichannel Near Infrared Spectroscopy

    PubMed Central

    Uehara, Toru; Ishige, Yoko

    2015-01-01

    This study aims to examine the association of frontal functioning with subclinical bipolar spectrum by a newly developed convenient method. We investigated subclinical bipolar tendency and frontal lobe activation during word productions using multi-channel near infrared spectroscopy. Participants: 44 healthy university students (mean ages 20.5 years old, and 29 female) gave their written informed consent, and we strictly protected privacy and anonymity was carefully preserved. A 13-items self-report questionnaire (Mood Disorders Questionnaire; MDQ) and a 16-channel near-infrared spectroscopy were used to compare frontal activations between two samples divided by median (4 points) of the total MDQ scores and to analyze correlations between relative changes of cerebral blood volume and bipolarity levels. There was no case suspected as bipolar disorders by MDQ screening (mean 3.4, max 10). Significant differences in lower activations were noted in the right and left pre-frontal cortex (PFC) with higher bipolarity scores using the specific software to analyze the NIRS waveform (P<0.05). Total MDQ were correlated significantly with frontal activation negatively in many channels; therefore, we conducted multiple linear regression to select significant frontal activations using the MDQ as a dependent variable. Stepwise method revealed that activation in left lateral PFC was negatively associated to bipolar tendency, and this regression model was significant (R2=0.10, F=4.5, P=0.04). Differences in frontal functioning suggest that subclinical bipolar tendencies might be related to left lateral PFC activations. It should be confirmed whether the identical pattern can be identified for clinical subjects with bipolar disorders. PMID:26605032

  18. Effects of naltrexone on firing activity of rat cortex neurons and its interactions with ethanol.

    PubMed

    Kozhechkin, S N; Mednikova, Yu S; Kolik, L G

    2013-09-01

    Naltrexone dose-dependently decreased neuron firing rate in the rat frontal cortex after intravenous (1-20 mg/kg) and microelectrophoretic administration. Microelectrophoretic applications of naltrexone reduced the excitatory neuronal response of neurons to low doses of ethanol (electroosmotic application) and potentiated depression of firing activity induced by ethanol in high doses. We concluded that opioid peptides take part in generation of spontaneous neuronal activity in the frontal cortex and neuronal excitation caused by ethanol in low doses. Naltrexone acts as a synergist of ethanol in its depressive effect on cortical neurons. PMID:24288728

  19. Source memory and frontal functioning in Parkinson's disease

    PubMed Central

    Drag, Lauren L.; Bieliauskas, Linas A.; Kaszniak, Alfred W.; Bohnen, Nicolaas I.; Glisky, Elizabeth L.

    2009-01-01

    The most extensively described pathological abnormality in Parkinson's disease (PD) is loss of dopaminergic neurons in the substantia nigra pars compacta and the ventral tegmental area, with degeneration of their striatal terminals. Because of the intimate connections between the striatum and the frontal lobes, individuals with PD often demonstrate impairments on those tasks relying on the prefrontal cortex (e.g., tests of executive functioning). Source memory, or memory for context, is believed to rely on the prefrontal cortex and has been previously associated with executive functioning performance, although it has received little attention in the PD literature. Executive functioning and source memory were measured in a group of nondemented PD patients and healthy control participants. Within the PD group, an anti-Parkinson's medication withdrawal manipulation was used to examine whether source memory was affected by phasic changes in dopamine levels. Compared to healthy control participants, PD patients were impaired in source memory (both on- and off-medication) and on a composite measure of executive functioning. Within the PD group, medication administration improved motor performance but did not have a significant effect on source memory. PMID:19402926

  20. Probabilistic functional tractography of the human cortex.

    PubMed

    David, Olivier; Job, Anne-Sophie; De Palma, Luca; Hoffmann, Dominique; Minotti, Lorella; Kahane, Philippe

    2013-10-15

    Single-pulse direct electrical stimulation of cortical regions in patients suffering from focal drug-resistant epilepsy who are explored using intracranial electrodes induces cortico-cortical potentials that can be used to infer functional and anatomical connectivity. Here, we describe a neuroimaging framework that allows development of a new probabilistic atlas of functional tractography of the human cortex from those responses. This atlas is unique because it allows inference in vivo of the directionality and latency of cortico-cortical connectivity, which are still largely unknown at the human brain level. In this technical note, we include 1535 stimulation runs performed in 35 adult patients. We use a case of frontal lobe epilepsy to illustrate the asymmetrical connectivity between the posterior hippocampal gyrus and the orbitofrontal cortex. In addition, as a proof of concept for group studies, we study the probabilistic functional tractography between the posterior superior temporal gyrus and the inferior frontal gyrus. In the near future, the atlas database will be continuously increased, and the methods will be improved in parallel, for more accurate estimation of features of interest. Generated probabilistic maps will be freely distributed to the community because they provide critical information for further understanding and modelling of large-scale brain networks. PMID:23707583

  1. Frontal sinus cholesterol granuloma: Case report

    PubMed Central

    Deep, Nicholas L.; Chaaban, Mohamad R.; Chaudhry, Ajaz L.

    2014-01-01

    A case report of a massive cholesterol granuloma (CG) of the frontal sinus in a 15-year-old male subject treated endoscopically is reported. CGs are slowly expanding, cystic lesions that are rarely observed in the frontal sinus. Frontal sinus CGs characteristically present with proptosis, diplopia, and a unilateral painless expanding mass above the orbit. Patients frequently report a history of chronic nasal obstruction or head trauma. Although the pathogenesis is unclear, it is likely multifactorial in etiology. Surgical resection via endoscopic sinus surgery has been gaining popularity because of the minimally invasive approach and lower rates of recurrence. PMID:24612824

  2. Damage to Left Frontal Regulatory Circuits Produces Greater Positive Emotional Reactivity in Frontotemporal Dementia

    PubMed Central

    Sturm, Virginia E.; Yokoyama, Jennifer S.; Eckart, Janet A.; Zakrzewski, Jessica; Rosen, Howard J.; Miller, Bruce L.; Seeley, William W.; Levenson, Robert W.

    2015-01-01

    Positive emotions foster social relationships and motivate thought and action. Dysregulation of positive emotion may give rise to debilitating clinical symptomatology such as mania, risk-taking, and disinhibition. Neuroanatomically, there is extensive evidence that the left hemisphere of the brain, and the left frontal lobe in particular, plays an important role in positive emotion generation. Although prior studies have found that left frontal injury decreases positive emotion, it is not clear whether selective damage to left frontal emotion regulatory systems can actually increase positive emotion. We measured happiness reactivity in 96 patients with frontotemporal dementia, a neurodegenerative disease that targets emotion-relevant neural systems and causes alterations in positive emotion (i.e., euphoria and jocularity), and in 34 healthy controls. Participants watched a film clip designed to elicit happiness and a comparison film clip designed to elicit sadness while their facial behavior, physiological reactivity, and self-reported emotional experience were monitored. Whole-brain voxel-based morphometry analyses revealed that atrophy in predominantly left hemisphere fronto-striatal emotion regulation systems including left ventrolateral prefrontal cortex, orbitofrontal cortex, anterior insula, and striatum (pFWE < .05) was associated with greater happiness facial behavior during the film. Atrophy in left anterior insula and bilateral frontopolar cortex was also associated with higher cardiovascular reactivity (i.e., heart rate and blood pressure) but not self-reported positive emotional experience during the happy film (p< .005, uncorrected). No regions emerged as being associated with greater sadness reactivity, which suggests that left-lateralized fronto-striatal atrophy is selectively associated with happiness dysregulation. Whereas previous models have proposed that left frontal injury decreases positive emotional responding, we argue that selective

  3. Damage to left frontal regulatory circuits produces greater positive emotional reactivity in frontotemporal dementia.

    PubMed

    Sturm, Virginia E; Yokoyama, Jennifer S; Eckart, Janet A; Zakrzewski, Jessica; Rosen, Howard J; Miller, Bruce L; Seeley, William W; Levenson, Robert W

    2015-03-01

    Positive emotions foster social relationships and motivate thought and action. Dysregulation of positive emotion may give rise to debilitating clinical symptomatology such as mania, risk-taking, and disinhibition. Neuroanatomically, there is extensive evidence that the left hemisphere of the brain, and the left frontal lobe in particular, plays an important role in positive emotion generation. Although prior studies have found that left frontal injury decreases positive emotion, it is not clear whether selective damage to left frontal emotion regulatory systems can actually increase positive emotion. We measured happiness reactivity in 96 patients with frontotemporal dementia (FTD), a neurodegenerative disease that targets emotion-relevant neural systems and causes alterations in positive emotion (i.e., euphoria and jocularity), and in 34 healthy controls. Participants watched a film clip designed to elicit happiness and a comparison film clip designed to elicit sadness while their facial behavior, physiological reactivity, and self-reported emotional experience were monitored. Whole-brain voxel-based morphometry (VBM) analyses revealed that atrophy in predominantly left hemisphere fronto-striatal emotion regulation systems including left ventrolateral prefrontal cortex, orbitofrontal cortex, anterior insula, and striatum was associated with greater happiness facial behavior during the film (pFWE < .05). Atrophy in left anterior insula and bilateral frontopolar cortex was also associated with higher cardiovascular reactivity (i.e., heart rate and blood pressure) but not self-reported positive emotional experience during the happy film (p < .005, uncorrected). No regions emerged as being associated with greater sadness reactivity, which suggests that left-lateralized fronto-striatal atrophy is selectively associated with happiness dysregulation. Whereas previous models have proposed that left frontal injury decreases positive emotional responding, we argue that

  4. Cranialization of the Frontal Sinus for Secondary Mucocele Prevention following Open Surgery for Benign Frontal Lesions

    PubMed Central

    Horowitz, Gilad; Amit, Moran; Ben-Ari, Oded; Gil, Ziv; Abergel, Abraham; Margalit, Nevo; Cavel, Oren; Wasserzug, Oshri; Fliss, Dan M.

    2013-01-01

    Objective To compare frontal sinus cranialization to obliteration for future prevention of secondary mucocele formation following open surgery for benign lesions of the frontal sinus. Study Design Retrospective case series. Setting Tertiary academic medical center. Patients Sixty-nine patients operated for benign frontal sinus pathology between 1994 and 2011. Interventions Open excision of benign frontal sinus pathology followed by either frontal obliteration (n = 41, 59%) or frontal cranialization (n = 28, 41%). Main Outcome Measures The prevalence of post-surgical complications and secondary mucocele formation were compiled. Results Pathologies included osteoma (n = 34, 49%), mucocele (n = 27, 39%), fibrous dysplasia (n = 6, 9%), and encephalocele (n = 2, 3%). Complications included skin infections (n = 6), postoperative cutaneous fistula (n = 1), telecanthus (n = 4), diplopia (n = 3), nasal deformity (n = 2) and epiphora (n = 1). None of the patients suffered from postoperative CSF leak, meningitis or pneumocephalus. Six patients, all of whom had previously undergone frontal sinus obliteration, required revision surgery due to secondary mucocele formation. Statistical analysis using non-inferiority test reveal that cranialization of the frontal sinus is non-inferior to obliteration for preventing secondary mucocele formation (P<0.0001). Conclusion Cranialization of the frontal sinus appears to be a good option for prevention of secondary mucocele development after open excision of benign frontal sinus lesions. PMID:24376760

  5. The impact of different aetiologies on the cognitive performance of frontal patients

    PubMed Central

    Cipolotti, Lisa; Healy, Colm; Chan, Edgar; Bolsover, Fay; Lecce, Francesca; White, Mark; Spanò, Barbara; Shallice, Tim; Bozzali, Marco

    2015-01-01

    Neuropsychological group study methodology is considered one of the primary methods to further understanding of the organisation of frontal ‘executive’ functions. Typically, patients with frontal lesions caused by stroke or tumours have been grouped together to obtain sufficient power. However, it has been debated whether it is methodologically appropriate to group together patients with neurological lesions of different aetiologies. Despite this debate, very few studies have directly compared the performance of patients with different neurological aetiologies on neuropsychological measures. The few that did included patients with both anterior and posterior lesions. We present the first comprehensive retrospective comparison of the impact of lesions of different aetiologies on neuropsychological performance in a large number of patients whose lesion solely affects the frontal cortex. We investigated patients who had a cerebrovascular accident (CVA), high (HGT) or low grade (LGT) tumour, or meningioma, all at the post-operative stage. The same frontal ‘executive’ (Raven's Advanced Progressive Matrices, Stroop Colour-Word Test, Letter Fluency-S; Trail Making Test Part B) and nominal (Graded Naming Test) tasks were compared. Patients' performance was compared across aetiologies controlling for age and NART IQ scores. Assessments of focal frontal lesion location, lesion volume, global brain atrophy and non-specific white matter (WM) changes were undertaken and compared across the four aetiology. We found no significant difference in performance between the four aetiology subgroups on the ‘frontal’ executive and nominal tasks. However, we found strong effects of premorbid IQ on all cognitive tasks and robust effects of age only on the frontal tasks. We also compared specific aetiology subgroups directly, as previously reported in the literature. Overall we found no significant differences in the performance of CVA and tumour patients, or LGT and HGT

  6. Reduced Numbers of Somatostatin Receptors in the Cerebral Cortex in Alzheimer's Disease

    NASA Astrophysics Data System (ADS)

    Flint Beal, M.; Mazurek, Michael F.; Tran, Vinh T.; Chattha, Geetinder; Bird, Edward D.; Martin, Joseph B.

    1985-07-01

    Somatostatin receptor concentrations were measured in patients with Alzheimer's disease and controls. In the frontal cortex (Brodmann areas 6, 9, and 10) and temporal cortex (Brodmann area 21), the concentrations of somatostatin in receptors in the patients were reduced to approximately 50 percent of control values. A 40 percent reduction was seen in the hippocampus, while no significant changes were found in the cingulate cortex, postcentral gyrus, temporal pole, and superior temporal gyrus. Scatchard analysis showed a reduction in receptor number rather than a change in affinity. Somatostatin-like immunoreactivity was significantly reduced in both the frontal and temporal cortex. Somatostatin-like immunoreactivity was linearly related to somatostatin-receptor binding in the cortices of Alzheimer's patients. These findings may reflect degeneration of postsynaptic neurons or cortical afferents in the patients' cerebral cortices. Alternatively, decreased somatostatinlike immunoreactivity in Alzheimer's disease might indicate increased release of somatostatin and down regulation of postsynaptic receptors.

  7. Surface vulnerability of cerebral cortex to major depressive disorder.

    PubMed

    Peng, Daihui; Shi, Feng; Li, Gang; Fralick, Drew; Shen, Ting; Qiu, Meihui; Liu, Jun; Jiang, Kaida; Shen, Dinggang; Fang, Yiru

    2015-01-01

    Major depressive disorder (MDD) is accompanied by atypical brain structure. This study first presents the alterations in the cortical surface of patients with MDD using multidimensional structural patterns that reflect different neurodevelopment. Sixteen first-episode, untreated patients with MDD and 16 matched healthy controls underwent a magnetic resonance imaging (MRI) scan. The cortical maps of thickness, surface area, and gyrification were examined using the surface-based morphometry (SBM) approach. Increase of cortical thickness was observed in the right posterior cingulate region and the parietal cortex involving the bilateral inferior, left superior parietal and right paracentral regions, while decreased thickness was noted in the parietal cortex including bilateral pars opercularis and left precentral region, as well as the left rostral-middle frontal regions in patients with MDD. Likewise, increased or decreased surface area was found in five sub-regions of the cingulate gyrus, parietal and frontal cortices (e.g., bilateral inferior parietal and superior frontal regions). In addition, MDD patients exhibited a significant hypergyrification in the right precentral and supramarginal region. This integrated structural assessment of cortical surface suggests that MDD patients have cortical alterations of the frontal, parietal and cingulate regions, indicating a vulnerability to MDD during earlier neurodevelopmental process. PMID:25793287

  8. Surface Vulnerability of Cerebral Cortex to Major Depressive Disorder

    PubMed Central

    Li, Gang; Fralick, Drew; Shen, Ting; Qiu, Meihui; Liu, Jun; Jiang, Kaida; Shen, Dinggang; Fang, Yiru

    2015-01-01

    Major depressive disorder (MDD) is accompanied by atypical brain structure. This study first presents the alterations in the cortical surface of patients with MDD using multidimensional structural patterns that reflect different neurodevelopment. Sixteen first-episode, untreated patients with MDD and 16 matched healthy controls underwent a magnetic resonance imaging (MRI) scan. The cortical maps of thickness, surface area, and gyrification were examined using the surface-based morphometry (SBM) approach. Increase of cortical thickness was observed in the right posterior cingulate region and the parietal cortex involving the bilateral inferior, left superior parietal and right paracentral regions, while decreased thickness was noted in the parietal cortex including bilateral pars opercularis and left precentral region, as well as the left rostral-middle frontal regions in patients with MDD. Likewise, increased or decreased surface area was found in five sub-regions of the cingulate gyrus, parietal and frontal cortices (e.g., bilateral inferior parietal and superior frontal regions). In addition, MDD patients exhibited a significant hypergyrification in the right precentral and supramarginal region. This integrated structural assessment of cortical surface suggests that MDD patients have cortical alterations of the frontal, parietal and cingulate regions, indicating a vulnerability to MDD during earlier neurodevelopmental process. PMID:25793287

  9. Human Frontal Lobes and AI Planning Systems

    NASA Technical Reports Server (NTRS)

    Levinson, Richard; Lum, Henry Jr. (Technical Monitor)

    1994-01-01

    Human frontal lobes are essential for maintaining a self-regulating balance between predictive and reactive behavior. This paper describes a system that integrates prediction and reaction based on neuropsychological theories of frontal lobe function. In addition to enhancing our understanding of deliberate action in humans' the model is being used to develop and evaluate the same properties in machines. First, the paper presents some background neuropsychology in order to set a general context. The role of frontal lobes is then presented by summarizing three theories which formed the basis for this work. The components of an artificial frontal lobe are then discussed from both neuropsychological and AI perspectives. The paper concludes by discussing issues and methods for evaluating systems that integrate planning and reaction.

  10. Frontal sinus recognition for human identification

    NASA Astrophysics Data System (ADS)

    Falguera, Juan Rogelio; Falguera, Fernanda Pereira Sartori; Marana, Aparecido Nilceu

    2008-03-01

    Many methods based on biometrics such as fingerprint, face, iris, and retina have been proposed for person identification. However, for deceased individuals, such biometric measurements are not available. In such cases, parts of the human skeleton can be used for identification, such as dental records, thorax, vertebrae, shoulder, and frontal sinus. It has been established in prior investigations that the radiographic pattern of frontal sinus is highly variable and unique for every individual. This has stimulated the proposition of measurements of the frontal sinus pattern, obtained from x-ray films, for skeletal identification. This paper presents a frontal sinus recognition method for human identification based on Image Foresting Transform and shape context. Experimental results (ERR = 5,82%) have shown the effectiveness of the proposed method.

  11. Rationale for Management of Frontal Sinus Fractures

    PubMed Central

    BANICA, Bogdan; ENE, Patricia; DABU, Aurelia; ENE, Razvan; CIRSTOIU, Catalin

    2013-01-01

    ABSTRACT The optimal treatment of frontal sinus fractures remains controversial. Multiple treatment options and algorithms have been proposed by multiple specialties throughout the years; however, the optimal method of frontal sinus repair has yet to be discovered. Overwhelming complications such as meningitis, encephalitis or brain abscess are quite uncommon nowadays. Nevertheless, late development of invasive mucoceles is not a rarity and therefore long-term follow-up is mandatory. PMID:24790677

  12. Beyond the sniffer: frontal sinuses in Carnivora.

    PubMed

    Curtis, Abigail A; Van Valkenburgh, Blaire

    2014-11-01

    Paranasal sinuses are some of the most poorly understood features of mammalian cranial anatomy. They are highly variable in presence and form among species, but their function is not well understood. The best-supported explanations for the function of sinuses is that they opportunistically fill mechanically unnecessary space, but that in some cases, sinuses in combination with the configuration of the frontal bone may improve skull performance by increasing skull strength and dissipating stresses more evenly. We used CT technology to investigate patterns in frontal sinus size and shape disparity among three families of carnivores: Canidae, Felidae, and Hyaenidae. We provide some of the first quantitative data on sinus morphology for these three families, and employ a novel method to quantify the relationship between three-dimensional sinus shape and skull shape. As expected, frontal sinus size and shape were more strongly correlated with frontal bone size and shape than with the morphology of the skull as a whole. However, sinus morphology was also related to allometric differences among families that are linked to biomechanical function. Our results support the hypothesis that frontal sinuses most often opportunistically fill space that is mechanically unnecessary, and they can facilitate cranial shape changes that reduce stress during feeding. Moreover, we suggest that the ability to form frontal sinuses allows species to modify skull function without compromising the performance of more functionally constrained regions such as the nasal chamber (heat/water conservation, olfaction), and braincase (housing the brain and sensory structures). PMID:25312364

  13. Apraxia, pantomime and the parietal cortex

    PubMed Central

    Niessen, E.; Fink, G.R.; Weiss, P.H.

    2014-01-01

    Apraxia, a disorder of higher motor cognition, is a frequent and outcome-relevant sequel of left hemispheric stroke. Deficient pantomiming of object use constitutes a key symptom of apraxia and is assessed when testing for apraxia. To date the neural basis of pantomime remains controversial. We here review the literature and perform a meta-analysis of the relevant structural and functional imaging (fMRI/PET) studies. Based on a systematic literature search, 10 structural and 12 functional imaging studies were selected. Structural lesion studies associated pantomiming deficits with left frontal, parietal and temporal lesions. In contrast, functional imaging studies associate pantomimes with left parietal activations, with or without concurrent frontal or temporal activations. Functional imaging studies that selectively activated parietal cortex adopted the most stringent controls. In contrast to previous suggestions, current analyses show that both lesion and functional studies support the notion of a left-hemispheric fronto-(temporal)-parietal network underlying pantomiming object use. Furthermore, our review demonstrates that the left parietal cortex plays a key role in pantomime-related processes. More specifically, stringently controlled fMRI-studies suggest that in addition to storing motor schemas, left parietal cortex is also involved in activating these motor schemas in the context of pantomiming object use. In addition to inherent differences between structural and functional imaging studies and consistent with the dedifferentiation hypothesis, the age difference between young healthy subjects (typically included in functional imaging studies) and elderly neurological patients (typically included in structural lesion studies) may well contribute to the finding of a more distributed representation of pantomiming within the motor-dominant left hemisphere in the elderly. PMID:24967158

  14. Cerebral cortex structure in prodromal Huntington disease.

    PubMed

    Nopoulos, Peggy C; Aylward, Elizabeth H; Ross, Christopher A; Johnson, Hans J; Magnotta, Vincent A; Juhl, Andrew R; Pierson, Ronald K; Mills, James; Langbehn, Douglas R; Paulsen, Jane S

    2010-12-01

    Neuroimaging studies of subjects who are gene-expanded for Huntington Disease, but not yet diagnosed (termed prodromal HD), report that the cortex is "spared," despite the decrement in striatal and cerebral white-matter volume. Measurement of whole-cortex volume can mask more subtle, but potentially clinically relevant regional changes in volume, thinning, or surface area. The current study addressed this limitation by evaluating cortical morphology of 523 prodromal HD subjects. Participants included 693 individuals enrolled in the PREDICT-HD protocol. Of these participants, 523 carried the HD gene mutation (prodromal HD group); the remaining 170 were non gene-expanded and served as the comparison group. Based on age and CAG repeat length, gene-expanded subjects were categorized as "Far from onset," "Midway to onset," "Near onset," and "already diagnosed." MRI scans were processed using FreeSurfer. Cortical volume, thickness, and surface area were not significantly different between the Far from onset group and controls. However, beginning in the Midway to onset group, the cortex showed significant volume decrement, affecting most the posterior and superior cerebral regions. This pattern progressed when evaluating the groups further into the disease process. Areas that remained mostly unaffected included ventral and medial regions of the frontal and temporal cortex. Morphologic changes were mostly in thinning as surface area did not substantially change in most regions. Early in the course of HD, the cortex shows changes that are manifest as cortical thinning and are most robust in the posterior and superior regions of the cerebrum. PMID:20688164

  15. Cerebral Cortex Structure in Prodromal Huntington Disease

    PubMed Central

    Nopoulos, Peggy C.; Aylward, Elizabeth H.; Ross, Christopher A.; Johnson, Hans J.; Magnotta, Vincent A.; Juhl, Andrew R.; Pierson, Ronald K.; Mills, James; Langbehn, Douglas R.; Paulsen, Jane S.

    2010-01-01

    Neuroimaging studies of subjects who are gene-expanded for Huntington Disease, but not yet diagnosed (termed prodromal HD), report that the cortex is “spared,” despite the decrement in striatal and cerebral white-matter volume. Measurement of whole-cortex volume can mask more subtle, but potentially clinically relevant regional changes in volume, thinning, or surface area. The current study addressed this limitation by evaluating cortical morphology of 523 prodromal HD subjects. Participants included 693 individuals enrolled in the PREDICT-HD protocol. Of these participants, 523 carried the HD gene mutation (prodromal HD group); the remaining 170 were non gene-expanded and served as the comparison group. Based on age and CAG repeat length, gene-expanded subjects were categorized as “Far from onset,” “Midway to onset,” “Near onset,” and “already diagnosed.” MRI scans were processed using FreeSurfer. Cortical volume, thickness, and surface area were not significantly different between the Far from onset group and controls. However, beginning in the Midway to onset group, the cortex showed significant volume decrement, affecting most the posterior and superior cerebral regions. This pattern progressed when evaluating the groups further into the disease process. Areas that remained mostly unaffected included ventral and medial regions of the frontal and temporal cortex. Morphologic changes were mostly in thinning as surface area did not substantially change in most regions. Early in the course of HD, the cortex shows changes that are manifest as cortical thinning and are most robust in the posterior and superior regions of the cerebrum. PMID:20688164

  16. Verbal suppression and strategy use: a role for the right lateral prefrontal cortex?

    PubMed

    Robinson, Gail A; Cipolotti, Lisa; Walker, David G; Biggs, Vivien; Bozzali, Marco; Shallice, Tim

    2015-04-01

    Verbal initiation, suppression and strategy generation/use are cognitive processes widely held to be supported by the frontal cortex. The Hayling Test was designed to tap these cognitive processes within the same sentence completion task. There are few studies specifically investigating the neural correlates of the Hayling Test but it has been primarily used to detect frontal lobe damage. This study investigates the components of the Hayling Test in a large sample of patients with unselected focal frontal (n = 60) and posterior (n = 30) lesions. Patients and controls (n = 40) matched for education, age and sex were administered the Hayling Test as well as background cognitive tests. The standard Hayling Test clinical measures (initiation response time, suppression response time, suppression errors and overall score), composite errors scores and strategy-based responses were calculated. Lesions were analysed by classical frontal/posterior subdivisions as well as a finer-grained frontal localization method and a specific contrast method that is somewhat analogous to voxel-based lesion mapping methods. Thus, patients with right lateral, left lateral and superior medial lesions were compared to controls and patients with right lateral lesions were compared to all other patients. The results show that all four standard Hayling Test clinical measures are sensitive to frontal lobe damage although only the suppression error and overall scores were specific to the frontal region. Although all frontal patients produced blatant suppression errors, a specific right lateral frontal effect was revealed for producing errors that were subtly wrong. In addition, frontal patients overall produced fewer correct responses indicative of developing an appropriate strategy but only the right lateral group showed a significant deficit. This problem in strategy attainment and implementation could explain, at least in part, the suppression error impairment. Contrary to previous studies

  17. Clinical-physiologic correlates of Alzheimer's disease and frontal lobe dementia

    SciTech Connect

    Jagust, W.J.; Reed, B.R.; Seab, J.P.; Kramer, J.H.; Budinger, T.F. )

    1989-01-01

    Thirty patients with degenerative dementia underwent clinical evaluation, neuropsychological testing, and single photon emission computed tomography (SPECT) with the blood flow tracer ({sup 123}I)-N-isopropyl-p-iodoamphetamine. Five of these patients were clinically and psychologically different from the others, demonstrating predominant behavioral disturbances with relative preservation of memory function. These five patients, who were felt to have a frontal lobe dementia (FLD), showed SPECT perfusion patterns which differed from the remaining 25 patients, who were diagnosed as having Alzheimer's disease (AD), and from 16 healthy control subjects. The FLD patients showed diminished perfusion in orbitofrontal, dorsolateral frontal, and temporal cortex relative to controls, while the AD patients showed lower perfusion in temporal and parietal cortex than controls. The FLD patients also showed hypoperfusion in both frontal cortical regions relative to AD patients. The pattern of performance on neuropsychological testing paralleled these differences in regional perfusion. These results suggest that clinical evaluation and physiological imaging may enable the differentiation of groups of degenerative dementia patients during life.

  18. Cortical surface complexity in frontal and temporal areas varies across subgroups of schizophrenia.

    PubMed

    Nenadic, Igor; Yotter, Rachel A; Sauer, Heinrich; Gaser, Christian

    2014-04-01

    Schizophrenia is assumed to be a neurodevelopmental disorder, which might involve disturbed development of the cerebral cortex, especially in frontal and medial temporal areas. Based on a novel spherical harmonics approach to measuring complexity of cortical folding, we applied a measure based on fractal dimension (FD) to investigate the heterogeneity of regional cortical surface abnormalities across subgroups of schizophrenia defined by symptom profiles. A sample of 87 patients with DSM-IV schizophrenia was divided into three subgroups (based on symptom profiles) with predominantly negative (n = 31), disorganized (n = 23), and paranoid (n = 33) symptoms and each compared to 108 matched healthy controls. While global FD measures were reduced in the right hemisphere of the negative and paranoid subgroups, regional analysis revealed marked heterogeneity of regional FD alterations. The negative subgroup showed most prominent reductions in left anterior cingulate, superior frontal, frontopolar, as well as right superior frontal and superior parietal cortices. The disorganized subgroup showed reductions in bilateral ventrolateral/orbitofrontal cortices, and several increases in the left hemisphere, including inferior parietal, middle temporal, and midcingulate areas. The paranoid subgroup showed only few changes, including decreases in the right superior parietal and left fusiform region, and increase in the left posterior cingulate cortex. Our findings suggest regional heterogeneity of cortical folding complexity, which might be related to biological subgroups of schizophrenia with differing degrees of altered cortical developmental pathology. PMID:23813686

  19. Aberrant functional connectivity differentiates retrosplenial cortex from posterior cingulate cortex in prodromal Alzheimer's disease.

    PubMed

    Dillen, Kim N H; Jacobs, Heidi I L; Kukolja, Juraj; von Reutern, Boris; Richter, Nils; Onur, Özgür A; Dronse, Julian; Langen, Karl-Josef; Fink, Gereon R

    2016-08-01

    The posterior cingulate cortex (PCC) is a key hub of the default mode network, a resting-state network involved in episodic memory, showing functional connectivity (FC) changes in Alzheimer's disease (AD). However, PCC is a cytoarchitectonically heterogeneous region. Specifically, the retrosplenial cortex (RSC), often subsumed under the PCC, is an area functionally and microanatomically distinct from PCC. To investigate FC patterns of RSC and PCC separately, we used resting-state functional magnetic resonance imaging in healthy aging participants, patients with subjective cognitive impairment, and prodromal AD. Compared to the other 2 groups, we found higher FC from RSC to frontal cortex in subjective cognitive impairment but higher FC to occipital cortex in prodromal AD. Conversely, FC from PCC to the lingual gyrus was higher in prodromal AD. Furthermore, data indicate that RSC and PCC are characterized by differential FC patterns represented by hub-specific interactions with memory and attentions scores in prodromal AD compared to cognitively normal individuals, possibly reflecting compensatory mechanisms for RSC and neurodegenerative processes for PCC. Data thus confirm and extend previous studies suggesting that the RSC is functionally distinct from PCC. PMID:27318139

  20. Unraveling the anxious mind: anxiety, worry, and frontal engagement in sustained attention versus off-task processing.

    PubMed

    Forster, Sophie; Nunez Elizalde, Anwar O; Castle, Elizabeth; Bishop, Sonia J

    2015-03-01

    Much remains unknown regarding the relationship between anxiety, worry, sustained attention, and frontal function. Here, we addressed this using a sustained attention task adapted for functional magnetic resonance imaging. Participants responded to presentation of simple stimuli, withholding responses to an infrequent "No Go" stimulus. Dorsolateral prefrontal cortex (DLPFC) activity to "Go" trials, and dorsal anterior cingulate (dACC) activity to "No Go" trials were associated with faster error-free performance; consistent with DLPFC and dACC facilitating proactive and reactive control, respectively. Trait anxiety was linked to reduced recruitment of these regions, slower error-free performance, and decreased frontal-thalamo-striatal connectivity. This indicates an association between trait anxiety and impoverished frontal control of attention, even when external distractors are absent. In task blocks where commission errors were made, greater DLPFC-precuneus and DLPFC-posterior cingulate connectivity were associated with both trait anxiety and worry, indicative of increased off-task thought. Notably, unlike trait anxiety, worry was not linked to reduced frontal-striatal-thalamo connectivity, impoverished frontal recruitment, or slowed responding during blocks without commission errors, contrary to accounts proposing a direct causal link between worry and impoverished attentional control. This leads us to propose a new model of the relationship between anxiety, worry and frontal engagement in attentional control versus off-task thought. PMID:24062316

  1. Interfering with the neural activity of mirror-related frontal areas impairs mentalistic inferences.

    PubMed

    Herbet, Guillaume; Lafargue, Gilles; Moritz-Gasser, Sylvie; Bonnetblanc, François; Duffau, Hugues

    2015-07-01

    According to recently proposed interactive dual-process theories, mentalizing abilities emerge from the coherent interaction between two physically distinct neural systems: (1) the mirror network, coding for the low-level embodied representations involved in pre-reflective sociocognitive processes and (2) the mentalizing network per se, which codes for higher level representations subtending the reflective attribution of psychological states. However, although the latest studies have shown that the core areas forming these two neurocognitive systems do indeed maintain effective connectivity during mentalizing, it is unclear whether an intact mirror system (and, more specifically, its anterior node, namely the posterior inferior frontal cortex) is a prerequisite for accurate mentalistic inferences. Intraoperative brain mapping via direct electrical stimulation offers a unique opportunity to address this issue. Electrical stimulation of the brain creates a "virtual" lesion, which provides functional information on well-defined parts of the cerebral cortex. In the present study, five patients were mapped in real time while they performed a mentalizing task. We found six responsive sites: four in the lateral part of the right pars opercularis and two in the dorsal part of the right pars triangularis. On the subcortical level, two additional sites were located within the white matter connectivity of the pars opercularis. Taken as a whole, our results suggest that the right inferior frontal cortex and its underlying axonal connectivity have a key role in mentalizing. Specifically, our findings support the hypothesis whereby transient, functional disruption of the mirror network influences higher order mentalistic inferences. PMID:24802379

  2. Evidence for inhibitory deficits in the prefrontal cortex in schizophrenia

    PubMed Central

    Radhu, Natasha; Garcia Dominguez, Luis; Farzan, Faranak; Richter, Margaret A.; Semeralul, Mawahib O.; Chen, Robert; Fitzgerald, Paul B.

    2015-01-01

    Abnormal gamma-aminobutyric acid inhibitory neurotransmission is a key pathophysiological mechanism underlying schizophrenia. Transcranial magnetic stimulation can be combined with electroencephalography to index long-interval cortical inhibition, a measure of GABAergic receptor-mediated inhibitory neurotransmission from the frontal and motor cortex. In previous studies we have reported that schizophrenia is associated with inhibitory deficits in the dorsolateral prefrontal cortex compared to healthy subjects and patients with bipolar disorder. The main objective of the current study was to replicate and extend these initial findings by evaluating long-interval cortical inhibition from the dorsolateral prefrontal cortex in patients with schizophrenia compared to patients with obsessive-compulsive disorder. A total of 111 participants were assessed: 38 patients with schizophrenia (average age: 35.71 years, 25 males, 13 females), 27 patients with obsessive-compulsive disorder (average age: 36.15 years, 11 males, 16 females) and 46 healthy subjects (average age: 33.63 years, 23 females, 23 males). Long-interval cortical inhibition was measured from the dorsolateral prefrontal cortex and motor cortex through combined transcranial magnetic stimulation and electroencephalography. In the dorsolateral prefrontal cortex, long-interval cortical inhibition was significantly reduced in patients with schizophrenia compared to healthy subjects (P = 0.004) and not significantly different between patients with obsessive-compulsive disorder and healthy subjects (P = 0.5445). Long-interval cortical inhibition deficits in the dorsolateral prefrontal cortex were also significantly greater in patients with schizophrenia compared to patients with obsessive-compulsive disorder (P = 0.0465). There were no significant differences in long-interval cortical inhibition across all three groups in the motor cortex. These results demonstrate that long-interval cortical inhibition deficits in the

  3. Orbitofrontal Cortex Volume and Brain Reward Response in Obesity

    PubMed Central

    Shott, Megan E.; Cornier, Marc-Andre; Mittal, Vijay A.; Pryor, Tamara L.; Orr, Joseph M.; Brown, Mark S.; Frank, Guido K.W.

    2014-01-01

    Background/Objectives What drives overconsumption of food is poorly understood. Alterations in brain structure and function could contribute to increased food seeking. Recently brain orbitofrontal cortex volume has been implicated in dysregulated eating but little is know how brain structure relates to function. Subjects/Methods We examined obese (n=18, age=28.7.4±8.3 years) and healthy control women (n=24, age=27.4±6.3 years) using a multimodal brain imaging approach. We applied magnetic resonance and diffusion tensor imaging to study brain gray and white matter volume as well as white matter integrity, and tested whether orbitofrontal cortex volume predicts brain reward circuitry activation in a taste reinforcement-learning paradigm that has been associated with dopamine function. Results Obese individuals displayed lower gray and associated white matter volumes (p<.05 family wise error (FWE)-small volume corrected) compared to controls in the orbitofrontal cortex, striatum, and insula. White matter integrity was reduced in obese individuals in fiber tracts including the external capsule, corona radiata, sagittal stratum, and the uncinate, inferior fronto-occipital, and inferior longitudinal fasciculi. Gray matter volume of the gyrus rectus at the medial edge of the orbitofrontal cortex predicted functional taste reward-learning response in frontal cortex, insula, basal ganglia, amygdala, hypothalamus and anterior cingulate cortex in control but not obese individuals. Conclusions This study indicates a strong association between medial orbitofrontal cortex volume and taste reinforcement-learning activation in the brain in control but not in obese women. Lower brain volumes in the orbitofrontal cortex and other brain regions associated with taste reward function as well as lower integrity of connecting pathways in obesity may support a more widespread disruption of reward pathways. The medial orbitofrontal cortex is an important structure in the termination of

  4. Mapping the Structural Core of Human Cerebral Cortex

    PubMed Central

    Hagmann, Patric; Cammoun, Leila; Gigandet, Xavier; Meuli, Reto; Honey, Christopher J; Wedeen, Van J; Sporns, Olaf

    2008-01-01

    Structurally segregated and functionally specialized regions of the human cerebral cortex are interconnected by a dense network of cortico-cortical axonal pathways. By using diffusion spectrum imaging, we noninvasively mapped these pathways within and across cortical hemispheres in individual human participants. An analysis of the resulting large-scale structural brain networks reveals a structural core within posterior medial and parietal cerebral cortex, as well as several distinct temporal and frontal modules. Brain regions within the structural core share high degree, strength, and betweenness centrality, and they constitute connector hubs that link all major structural modules. The structural core contains brain regions that form the posterior components of the human default network. Looking both within and outside of core regions, we observed a substantial correspondence between structural connectivity and resting-state functional connectivity measured in the same participants. The spatial and topological centrality of the core within cortex suggests an important role in functional integration. PMID:18597554

  5. Modulation of inferotemporal cortex activation during verbal working memory maintenance

    PubMed Central

    Fiebach, Christian J.; Rissman, Jesse; D'Esposito, Mark

    2015-01-01

    Summary Regions of the left inferotemporal cortex are involved in visual word recognition and semantics. We utilized functional magnetic resonance imaging to localize an inferotemporal language area and to demonstrate that this area is involved in the active maintenance of visually presented words in working memory. Maintenance activity in this inferotemporal area showed an effect of memory load for words, but not pseudowords. The selective modulation of this language-related inferotemporal area for the maintenance of words, in the absence of visual input, is accompanied by an increased functional connectivity with left prefrontal cortex. These results are the first demonstration of an involvement of inferotemporal cortex in verbal working memory. They provide neurophysiological support for the notion that nonphonological language representations can be recruited in the service of verbal working memory. More generally, they suggest that verbal working memory should be conceptualized as the frontally-guided, sustained activation of pre-existing cortical language representations. PMID:16846859

  6. Frontal Cortical Asymmetry May Partially Mediate the Influence of Social Power on Anger Expression.

    PubMed

    Li, Dongdong; Wang, Changming; Yin, Qin; Mao, Mengchai; Zhu, Chaozhe; Huang, Yuxia

    2016-01-01

    When irritated by other people, powerful people usually tend to express their anger explicitly and directly, whereas people in less powerful positions are more likely not to show their feelings freely. The neural mechanism behind power and its influence on expression tendency has been scarcely explored. This study recorded frontal EEG activity at rest and frontal EEG activation while participants were engaged in a writing task describing an anger-eliciting event, in which they were irritated by people with higher or lower social power. Participants' anger levels and expression inclination levels were self-reported on nine-point visual analog Likert scales, and also rated by independent raters based on the essays they had written. The results showed that high social power was indeed associated with greater anger expression tendency and greater left frontal activation than low social power. This is in line with the approach-inhibition theory of power. The mid-frontal asymmetric activation served as a partial mediator between social power and expression inclination. This effect may relate to the functions of the prefrontal cortex, which is in charge of information integration and evaluation and the control of motivation direction, as reported by previous studies. PMID:26869972

  7. Frontal and parietal theta burst TMS impairs working memory for visual-spatial conjunctions.

    PubMed

    Morgan, Helen M; Jackson, Margaret C; van Koningsbruggen, Martijn G; Shapiro, Kimron L; Linden, David E J

    2013-03-01

    In tasks that selectively probe visual or spatial working memory (WM) frontal and posterior cortical areas show a segregation, with dorsal areas preferentially involved in spatial (e.g. location) WM and ventral areas in visual (e.g. object identity) WM. In a previous fMRI study [1], we showed that right parietal cortex (PC) was more active during WM for orientation, whereas left inferior frontal gyrus (IFG) was more active during colour WM. During WM for colour-orientation conjunctions, activity in these areas was intermediate to the level of activity for the single task preferred and non-preferred information. To examine whether these specialised areas play a critical role in coordinating visual and spatial WM to perform a conjunction task, we used theta burst transcranial magnetic stimulation (TMS) to induce a functional deficit. Compared to sham stimulation, TMS to right PC or left IFG selectively impaired WM for conjunctions but not single features. This is consistent with findings from visual search paradigms, in which frontal and parietal TMS selectively affects search for conjunctions compared to single features, and with combined TMS and functional imaging work suggesting that parietal and frontal regions are functionally coupled in tasks requiring integration of visual and spatial information. Our results thus elucidate mechanisms by which the brain coordinates spatially segregated processing streams and have implications beyond the field of working memory. PMID:22483548

  8. Traumatic brain injury and the frontal lobes: what can we gain with diffusion tensor imaging?

    PubMed

    Zappalà, Giuseppe; Thiebaut de Schotten, Michel; Eslinger, Paul J

    2012-02-01

    Traumatic brain injury (TBI) is a leading cause of death in the young population and long-term disability in relation to pervasive cognitive-behavioural disturbances that follow frontal lobe damage. To date, emphasis has been placed primarily on the clinical correlates of frontal cortex damage, whilst identification of the contribution of subjacent white matter lesion is less clear. Our poor understanding of white matter pathology in TBI is primarily due to the low sensitivity of conventional neuroimaging to identify pathological changes in less severe traumatic injury and the lack of methods to localise white matter pathology onto individual frontal lobe connections. In this paper we focus on the potential contribution of diffusion tensor imaging (DTI) to TBI. Our review of the current literature supports the conclusion that DTI is particularly sensitive to changes in the microstructure of frontal white matter, thus providing a valuable biomarker of the severity of traumatic injury and prognostic indicator of recovery of function. Furthermore we propose an atlas approach to TBI to map white matter lesions onto individual tracts. In the cases presented here we showed a direct correspondence between the clinical manifestations of the patients and the damage to specific white matter tracts. We are confident that in the near future the application of DTI to TBI will improve our understanding of the complex and heterogeneous clinical symptomatology which follows a TBI, especially mild and moderate head injury, which still represents 70-80% of all clinical population. PMID:21813118

  9. Frontal Cortical Asymmetry May Partially Mediate the Influence of Social Power on Anger Expression

    PubMed Central

    Li, Dongdong; Wang, Changming; Yin, Qin; Mao, Mengchai; Zhu, Chaozhe; Huang, Yuxia

    2016-01-01

    When irritated by other people, powerful people usually tend to express their anger explicitly and directly, whereas people in less powerful positions are more likely not to show their feelings freely. The neural mechanism behind power and its influence on expression tendency has been scarcely explored. This study recorded frontal EEG activity at rest and frontal EEG activation while participants were engaged in a writing task describing an anger-eliciting event, in which they were irritated by people with higher or lower social power. Participants’ anger levels and expression inclination levels were self-reported on nine-point visual analog Likert scales, and also rated by independent raters based on the essays they had written. The results showed that high social power was indeed associated with greater anger expression tendency and greater left frontal activation than low social power. This is in line with the approach-inhibition theory of power. The mid-frontal asymmetric activation served as a partial mediator between social power and expression inclination. This effect may relate to the functions of the prefrontal cortex, which is in charge of information integration and evaluation and the control of motivation direction, as reported by previous studies. PMID:26869972

  10. [Normal aging of frontal lobe functions].

    PubMed

    Calso, Cristina; Besnard, Jérémy; Allain, Philippe

    2016-03-01

    Normal aging in individuals is often associated with morphological, metabolic and cognitive changes, which particularly concern the cerebral frontal regions. Starting from the "frontal lobe hypothesis of cognitive aging" (West, 1996), the present review is based on the neuroanatomical model developed by Stuss (2008), introducing four categories of frontal lobe functions: executive control, behavioural and emotional self-regulation and decision-making, energization and meta-cognitive functions. The selected studies only address the changes of one at least of these functions. The results suggest a deterioration of several cognitive frontal abilities in normal aging: flexibility, inhibition, planning, verbal fluency, implicit decision-making, second-order and affective theory of mind. Normal aging seems also to be characterised by a general reduction in processing speed observed during neuropsychological assessment (Salthouse, 1996). Nevertheless many cognitive functions remain preserved such as automatic or non-conscious inhibition, specific capacities of flexibility and first-order theory of mind. Therefore normal aging doesn't seem to be associated with a global cognitive decline but rather with a selective change in some frontal systems, conclusion which should be taken into account for designing caring programs in normal aging. PMID:27005339

  11. “It's Not What You Say, But How You Say it”: A Reciprocal Temporo-frontal Network for Affective Prosody

    PubMed Central

    Leitman, David I.; Wolf, Daniel H.; Ragland, J. Daniel; Laukka, Petri; Loughead, James; Valdez, Jeffrey N.; Javitt, Daniel C.; Turetsky, Bruce I.; Gur, Ruben C.

    2009-01-01

    Humans communicate emotion vocally by modulating acoustic cues such as pitch, intensity and voice quality. Research has documented how the relative presence or absence of such cues alters the likelihood of perceiving an emotion, but the neural underpinnings of acoustic cue-dependent emotion perception remain obscure. Using functional magnetic resonance imaging in 20 subjects we examined a reciprocal circuit consisting of superior temporal cortex, amygdala and inferior frontal gyrus that may underlie affective prosodic comprehension. Results showed that increased saliency of emotion-specific acoustic cues was associated with increased activation in superior temporal cortex [planum temporale (PT), posterior superior temporal gyrus (pSTG), and posterior superior middle gyrus (pMTG)] and amygdala, whereas decreased saliency of acoustic cues was associated with increased inferior frontal activity and temporo-frontal connectivity. These results suggest that sensory-integrative processing is facilitated when the acoustic signal is rich in affective information, yielding increased activation in temporal cortex and amygdala. Conversely, when the acoustic signal is ambiguous, greater evaluative processes are recruited, increasing activation in inferior frontal gyrus (IFG) and IFG STG connectivity. Auditory regions may thus integrate acoustic information with amygdala input to form emotion-specific representations, which are evaluated within inferior frontal regions. PMID:20204074

  12. Verb generation in patients with focal frontal lesions: A neuropsychological test of neuroimaging findings

    PubMed Central

    Thompson-Schill, Sharon L.; Swick, Diane; Farah, Martha J.; D’Esposito, Mark; Kan, Irene P.; Knight, Robert T.

    1998-01-01

    What are the neural bases of semantic memory? Traditional beliefs that the temporal lobes subserve the retrieval of semantic knowledge, arising from lesion studies, have been recently called into question by functional neuroimaging studies finding correlations between semantic retrieval and activity in left prefrontal cortex. Has neuroimaging taught us something new about the neural bases of cognition that older methods could not reveal or has it merely identified brain activity that is correlated with but not causally related to the process of semantic retrieval? We examined the ability of patients with focal frontal lesions to perform a task commonly used in neuroimaging experiments, the generation of semantically appropriate action words for concrete nouns, and found evidence of the necessity of the left inferior frontal gyrus for certain components of the verb generation task. Notably, these components did not include semantic retrieval per se. PMID:9861060

  13. Theta lingua franca: a common mid-frontal substrate for action monitoring processes.

    PubMed

    Cavanagh, James F; Zambrano-Vazquez, Laura; Allen, John J B

    2012-02-01

    We present evidence that a multitude of mid-frontal event-related potential (ERP) components partially reflect a common theta band oscillatory process. Specifically, mid-frontal ERP components in the N2 time range and error-related negativity time range are parsimoniously characterized as reflections of theta band activities. Forty participants completed three different tasks with varying stimulus-response demands. Permutation tests were used to identify the dominant time-frequency responses of stimulus- and response-locked conditions as well as the enhanced responses to novelty, conflict, punishment, and error. A dominant theta band feature was found in all conditions, and both ERP component amplitudes and theta power measures were similarly modulated by novelty, conflict, punishment, and error. The findings support the hypothesis that generic and reactive medial prefrontal cortex processes are parsimoniously reflected by theta band activities. PMID:22091878

  14. Performance on Cambridge Neuropsychological Test Automated Battery Subtests Sensitive to Frontal Lobe Function in People with Autistic Disorder: Evidence from the Collaborative Programs of Excellence in Autism Network

    ERIC Educational Resources Information Center

    Ozonoff, Sally; Cook, Ian; Coon, Hilary; Dawson, Geraldine; Joseph, Robert M.; Klin, Ami; McMahon, William M.; Minshew, Nancy; Munson, Jeffrey A.

    2004-01-01

    Recent structural and functional imaging work, as well as neuropathology and neuropsychology studies, provide strong empirical support for the involvement of frontal cortex in autism. The Cambridge Neuropsychological Test Automated Battery (CANTAB) is a computer-administered set of neuropsychological tests developed to examine specific components…

  15. Frontal-subcortical circuitry and behavior

    PubMed Central

    Bonelli, Raphael M.; Cummings, Jeffrey L.

    2007-01-01

    The neuropsychiatric manifestations of neurodegenerative diseases are closely linked to neurocircuitry defects. Frontal-subcortical circuits, in particular, are effector mechanisms that allow the organism to act on its environment In this paper, we present the three main frontal-subcortical circuits: the dorsolateral prefrontal circuit allows the organization of information to facilitate a response; the anterior cingulate circuit is required for motivated behavior; and the orbitofrontal circuit allows the integration of limbic and emotional information into behavioral responses. Impaired executive functions, apathy, and impulsivity are hallmarks of frontal-subcortical circuit dysfunction. A variety of other neuropsychiatrie disorders, such as Tourette's syndrome, Huntington's disease, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, schizophrenia, and mood disorders may result from disturbances that have a direct or indirect impact on the integrity or functioning of these loops. PMID:17726913

  16. Cephalic aura after frontal lobe resection.

    PubMed

    Kakisaka, Yosuke; Jehi, Lara; Alkawadri, Rafeed; Wang, Zhong I; Enatsu, Rei; Mosher, John C; Dubarry, Anne-Sophie; Alexopoulos, Andreas V; Burgess, Richard C

    2014-08-01

    A cephalic aura is a common sensory aura typically seen in frontal lobe epilepsy. The generation mechanism of cephalic aura is not fully understood. It is hypothesized that to generate a cephalic aura extensive cortical areas need to be excited. We report a patient who started to have cephalic aura after right frontal lobe resection. Magnetoencephalography (MEG) showed interictal spike and ictal change during cephalic aura, both of which were distributed in the right frontal region, and the latter involved much more widespread areas than the former on MEG sensors. The peculiar seizure onset pattern may indicate that surgical modification of the epileptic network was related to the appearance of cephalic aura. We hypothesize that generation of cephalic aura may be associated with more extensive cortical involvement of epileptic activity than that of interictal activity, in at least a subset of cases. PMID:24613491

  17. Frontal-thalamic circuits associated with language

    PubMed Central

    Barbas, Helen; García-Cabezas, Miguel Ángel; Zikopoulos, Basilis

    2012-01-01

    Thalamic nuclei associated with language including the ventral lateral, ventral anterior, intralaminar and mediodorsal form a hub that uniquely receives the output of the basal ganglia and cerebellum, and is connected with frontal (premotor and prefrontal) cortices through two parallel circuits: a thalamic pathway targets the middle frontal cortical layers focally, and the other innervates widely cortical layer 1, poised to recruit other cortices and thalamic nuclei for complex cognitive operations. Return frontal pathways to the thalamus originate from cortical layers 6 and 5. Information through this integrated thalamo-cortical system is gated by the inhibitory thalamic reticular nucleus and modulated by dopamine, representing a specialization in primates. The intricate dialogue of distinct thalamic nuclei with the basal ganglia, cerebellum, and specific dorsolateral prefrontal and premotor cortices associated with language, suggests synergistic roles in the complex but seemingly effortless sequential transformation of cognitive operations for speech production in humans. PMID:23211411

  18. Timing Tasks Synchronize Cerebellar and Frontal Ramping Activity and Theta Oscillations: Implications for Cerebellar Stimulation in Diseases of Impaired Cognition

    PubMed Central

    Parker, Krystal L.

    2016-01-01

    Timing is a fundamental and highly conserved mammalian capability, yet the underlying neural mechanisms are widely debated. Ramping activity of single neurons that gradually increase or decrease activity to encode the passage of time has been speculated to predict a behaviorally relevant temporal event. Cue-evoked low-frequency activity has also been implicated in temporal processing. Ramping activity and low-frequency oscillations occur throughout the brain and could indicate a network-based approach to timing. Temporal processing requires cognitive mechanisms of working memory, attention, and reasoning, which are dysfunctional in neuropsychiatric disease. Therefore, timing tasks could be used to probe cognition in animals with disease phenotypes. The medial frontal cortex and cerebellum are involved in cognition. Cerebellar stimulation has been shown to influence medial frontal activity and improve cognition in schizophrenia. However, the mechanism underlying the efficacy of cerebellar stimulation is unknown. Here, we discuss how timing tasks can be used to probe cerebellar interactions with the frontal cortex and the therapeutic potential of cerebellar stimulation. The goal of this theory and hypothesis manuscript is threefold. First, we will summarize evidence indicating that in addition to motor learning, timing tasks involve cognitive processes that are present within both the cerebellum and medial frontal cortex. Second, we propose methodologies to investigate the connections between these areas in patients with Parkinson’s disease, autism, and schizophrenia. Lastly, we hypothesize that cerebellar transcranial stimulation may rescue medial frontal ramping activity, theta oscillations, and timing abnormalities, thereby restoring executive function in diseases of impaired cognition. This hypothesis could inspire the use of timing tasks as biomarkers for neuronal and cognitive abnormalities in neuropsychiatric disease and promote the therapeutic potential of

  19. Neural network underlying ictal pouting ("chapeau de gendarme") in frontal lobe epilepsy.

    PubMed

    Souirti, Zouhayr; Landré, Elisabeth; Mellerio, Charles; Devaux, Bertrand; Chassoux, Francine

    2014-08-01

    In order to determine the anatomical neural network underlying ictal pouting (IP), with the mouth turned down like a "chapeau de gendarme", in frontal lobe epilepsy (FLE), we reviewed the video-EEG recordings of 36 patients with FLE who became seizure-free after surgery. We selected the cases presenting IP, defined as a symmetrical and sustained (>5s) lowering of labial commissures with contraction of chin, mimicking an expression of fear, disgust, or menace. Ictal pouting was identified in 11 patients (8 males; 16-48 years old). We analyzed the clinical semiology, imaging, and electrophysiological data associated with IP, including FDG-PET in 10 and SEEG in 9 cases. In 37 analyzed seizures (2-7/patient), IP was an early symptom, occurring during the first 10s in 9 cases. The main associated features consisted of fear, anguish, vegetative disturbances, behavioral disorders (sudden agitation, insults, and fighting), tonic posturing, and complex motor activities. The epileptogenic zone assessed by SEEG involved the mesial frontal areas, especially the anterior cingulate cortex (ACC) in 8 patients, whereas lateral frontal onset with an early spread to the ACC was seen in the other patient. Ictal pouting associated with emotional changes and hypermotor behavior had high localizing value for rostroventral "affective" ACC, whereas less intense facial expressions were related to the dorsal "cognitive" ACC. Fluorodeoxyglucose positron emission tomography demonstrated the involvement of both the ACC and lateral cortex including the anterior insula in all cases. We propose that IP is sustained by reciprocal mesial and lateral frontal interactions involved in emotional and cognitive processes, in which the ACC plays a pivotal role. PMID:25108117

  20. The frontal method in hydrodynamics simulations

    USGS Publications Warehouse

    Walters, R.A.

    1980-01-01

    The frontal solution method has proven to be an effective means of solving the matrix equations resulting from the application of the finite element method to a variety of problems. In this study, several versions of the frontal method were compared in efficiency for several hydrodynamics problems. Three basic modifications were shown to be of value: 1. Elimination of equations with boundary conditions beforehand, 2. Modification of the pivoting procedures to allow dynamic management of the equation size, and 3. Storage of the eliminated equations in a vector. These modifications are sufficiently general to be applied to other classes of problems. ?? 1980.

  1. Frontal Polymerization in Microgravity Summary of Research

    NASA Technical Reports Server (NTRS)

    Pojman, John A.

    2002-01-01

    The project began with frontal polymerization (FP). We studied many aspects of FP on the ground and performed two successful weeks of flying on the KC-135. The project evolved into the current flight investigation, Transient Interfacial Phenomena in Miscible Polymer Systems (TIPMPS), as we recognized that an essential question could best be studied using a non-frontal approach. We present detailed results from our ground-based work on FP, KC-135 results and the background, justification and numerical work for the TIPMPS project.

  2. [Simple partial frontal nonconvulsive status epilepticus].

    PubMed

    Thomas, P; Mottin, Y

    1997-07-01

    Non convulsive status epilepticus (NCSE) of frontal origin is a rare cause of mental confusion. The present case of possible frontal-onset NCSE proved to have a neuropsychological examination that was suggestive either of a disruption of attentional function or a left prefrontal dysfunction, exhibiting disturbances of immediate memory and logical programmation, perseverations and affective disinhibition. Vigilance was not impaired. This case was therefore, on a nosographic point of view, more consistent with a simple partial status epilepticus with cognitive and affective symptomatology rather than with a complex partial status epilepticus of extra-temporal origin. PMID:9684010

  3. Altered functional connectivity of the insular cortex across prefrontal networks in cocaine addiction.

    PubMed

    Cisler, Josh M; Elton, Amanda; Kennedy, Ashley P; Young, Jonathan; Smitherman, Sonet; Andrew James, George; Kilts, Clinton D

    2013-07-30

    Interoception is theorized to be an important process mediating substance use disorders, and the insular cortex is recognized as a core neural region supporting interoception. The purpose of this study was to compare the integration of the insular cortex into prefrontal-related resting-state networks between individuals with cocaine dependence and healthy controls. Participants comprised 41 patients with cocaine dependence and 19 controls who underwent a resting-state 3-T functional magnetic resonance imaging scan. Individuals with cocaine dependence demonstrated altered functional connectivity of the insular cortex, predominantly the right insular cortex, with all eight prefrontal-related resting-state networks identified through Independent Component Analysis (ICA). A conjunction analysis demonstrated that the right insular cortex was the neural region with the highest number of common group differences across the networks. There was no evidence that insular cortex connectivity commonly differed between groups for non-prefrontal-related networks. Further, seed-based functional connectivity analyses extended the network analyses and indicated that cocaine dependence was associated with greater connectivity of the right insula with the dorsomedial prefrontal cortex, inferior frontal gyrus, and bilateral dorsolateral prefrontal cortex. These data support the hypothesis that cocaine dependence is related to altered functional interactions of the insular cortex with prefrontal networks. The results suggest possible neural mechanisms by which the insular cortex and interoceptive information influence cognitive control and decision-making processes presumably mediated by prefrontal networks in the cocaine dependence process. PMID:23684980

  4. Exploratory metabolomic analyses reveal compounds correlated with lutein concentration in frontal cortex, hippocampus, and occipital cortex of human infant brain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with...

  5. Frontal top-down signals increase coupling of auditory low-frequency oscillations to continuous speech in human listeners.

    PubMed

    Park, Hyojin; Ince, Robin A A; Schyns, Philippe G; Thut, Gregor; Gross, Joachim

    2015-06-15

    Humans show a remarkable ability to understand continuous speech even under adverse listening conditions. This ability critically relies on dynamically updated predictions of incoming sensory information, but exactly how top-down predictions improve speech processing is still unclear. Brain oscillations are a likely mechanism for these top-down predictions [1, 2]. Quasi-rhythmic components in speech are known to entrain low-frequency oscillations in auditory areas [3, 4], and this entrainment increases with intelligibility [5]. We hypothesize that top-down signals from frontal brain areas causally modulate the phase of brain oscillations in auditory cortex. We use magnetoencephalography (MEG) to monitor brain oscillations in 22 participants during continuous speech perception. We characterize prominent spectral components of speech-brain coupling in auditory cortex and use causal connectivity analysis (transfer entropy) to identify the top-down signals driving this coupling more strongly during intelligible speech than during unintelligible speech. We report three main findings. First, frontal and motor cortices significantly modulate the phase of speech-coupled low-frequency oscillations in auditory cortex, and this effect depends on intelligibility of speech. Second, top-down signals are significantly stronger for left auditory cortex than for right auditory cortex. Third, speech-auditory cortex coupling is enhanced as a function of stronger top-down signals. Together, our results suggest that low-frequency brain oscillations play a role in implementing predictive top-down control during continuous speech perception and that top-down control is largely directed at left auditory cortex. This suggests a close relationship between (left-lateralized) speech production areas and the implementation of top-down control in continuous speech perception. PMID:26028433

  6. Visual masking with frontally applied pre-stimulus TMS and its subject-specific neural correlates.

    PubMed

    Rutiku, Renate; Tulver, Kadi; Aru, Jaan; Bachmann, Talis

    2016-07-01

    The visibility of a visual target stimulus depends on the local state of the early visual cortex shortly before the stimulus itself is presented. This view is supported by the observation that occipitally applied pre-stimulus TMS can disrupt subsequent information processing leading to visual masking effects. According to another line of accumulating evidence, however, global pre-stimulus connectivity patterns could be as crucial as local cortical states. In line with the latter view we show that pre-stimulus masking occurs even if TMS is directed to the frontal cortex. Importantly, the individual extent of this effect is strongly correlated with the subject-specific peak latency of a late positive TMS-evoked potential. Our results thus suggest a third type of masking occurring neither through direct interaction with visual areas nor by a modal visual masking input. Our results also shed light on the inter-individual differences in TMS research in general. PMID:27026655

  7. Action sequencing deficit following frontal lobe lesion.

    PubMed

    Zanini, Sergio; Rumiati, Raffaella I; Shallice, Tim

    2002-01-01

    Frontal lobe patients carried out temporal sequencing tasks related to actions that differed in terms of their abstractness using both verbal and pictorial presentations. A generalized impairment was found: neither a type of action effect nor a modality of item presentation effect was present. The patients also carried out a corresponding action production task and produced actions quickly and without errors. The frontal lobe patients were also spared in generating verbal descriptions of actions: they were as accurate as normal controls both in terms of the details reported and in maintaining the temporal sequence. It has been argued that the difficulty in processing the temporal dimensions of actions following frontal lobe lesions is due to some form of disruption of the action representation. However, no action representational deficits were present in our frontal lobe patients. Thus, they cannot account for our findings. On the contrary, we suggest that the action sequencing deficit was a consequence of the difficulties patients experienced in rejecting wrong alternatives presented by the stimulus situation. PMID:11997488

  8. Nail Involvement in Frontal Fibrosing Alopecia

    PubMed Central

    Macpherson, Melanie; Hohendorf-Ansari, Parinaz; Trüeb, Ralph Michel

    2015-01-01

    A case of frontal fibrosing alopecia with nail involvement is presented. Nail involvement provides evidence for underlying lichen planus, and that the disease represents a rather generalized than localized process. Favorable response of the scalp condition to oral dutasteride points to an inflammatory reaction on the background of androgenetic alopecia. PMID:26180450

  9. Union, States Wage Frontal Attack on NCLB

    ERIC Educational Resources Information Center

    Keller, Bess; Sack, Joetta L.

    2005-01-01

    Widespread sniping at the Bush administration's centerpiece education law escalated into a frontal attack as the nation's largest teachers' union. Several school districts sued federal officials over the measure, just a day after the Utah legislature approved a bill challenging the reach of the law. The National Education Association's suit…

  10. Infant Frontal Asymmetry Predicts Child Emotional Availability

    ERIC Educational Resources Information Center

    Licata, Maria; Paulus, Markus; Kühn-Popp, Nina; Meinhardt, Jorg; Sodian, Beate

    2015-01-01

    While factors influencing maternal emotional availability (EA) have been well investigated, little is known about the development of child EA. The present longitudinal study investigated the role of frontal brain asymmetry in young children with regard to child EA (child responsiveness and involvement) in mother-child interaction in a sample of 28…

  11. Nail Involvement in Frontal Fibrosing Alopecia.

    PubMed

    Macpherson, Melanie; Hohendorf-Ansari, Parinaz; Trüeb, Ralph Michel

    2015-01-01

    A case of frontal fibrosing alopecia with nail involvement is presented. Nail involvement provides evidence for underlying lichen planus, and that the disease represents a rather generalized than localized process. Favorable response of the scalp condition to oral dutasteride points to an inflammatory reaction on the background of androgenetic alopecia. PMID:26180450

  12. Music Shifts Frontal EEG in Depressed Adolescents.

    ERIC Educational Resources Information Center

    Field, Tiffany; Martinez, Alex; Nawrocki, Thomas; Pickens, Jeffrey; Fox, Nathan A.; Schanberg, Saul

    1998-01-01

    Fourteen chronically depressed female adolescents listened to rock music for a 23-minute session. EEG was recorded and saliva samples were collected to determine the effects of the music on stress hormone cortisol levels. No differences were reported for mood state; however, cortisol levels decreased and relative right-frontal activation was…

  13. Affective Aprosodia from a Medial Frontal Stroke

    ERIC Educational Resources Information Center

    Heilman, Kenneth M.; Leon, Susan A.; Rosenbek, John C.

    2004-01-01

    Background and objectives: Whereas injury to the left hemisphere induces aphasia, injury to the right hemisphere's perisylvian region induces an impairment of emotional speech prosody (affective aprosodia). Left-sided medial frontal lesions are associated with reduced verbal fluency with relatively intact comprehension and repetition…

  14. Why do patients with neurodegenerative frontal syndrome fail to answer: 'In what way are an orange and a banana alike?'.

    PubMed

    Lagarde, Julien; Valabrègue, Romain; Corvol, Jean-Christophe; Garcin, Béatrice; Volle, Emmanuelle; Le Ber, Isabelle; Vidailhet, Marie; Dubois, Bruno; Levy, Richard

    2015-02-01

    Concept formation is the ability to create an abstract link between dissimilar objects or thoughts and is crucial for abstract and creative thinking. This process is related to the integrity of the prefrontal cortex, given the altered performances reported in patients with frontal damage, particularly those suffering from the behavioural variant of frontotemporal dementia. However, the cognitive mechanisms and neural bases of verbal concept formation are not clearly understood. The present study was aimed at addressing the following unresolved issues regarding concept formation in the field of neurology and cognitive neuroscience: (i) Are alterations in concept formation specific to frontotemporal dementia or are they also present in other cortical neurodegenerative disorders such as Alzheimer's disease? (ii) Is impaired performance in concept formation due to cortical lesions specific to frontotemporal dementia or to a cortico-subcortical frontal syndrome? and (iii) What are the cognitive mechanisms and neural bases underlying concept formation? To address these questions, we designed the Verbal Concept Formation Task, an experimental paradigm based on the similarities test. Patients presenting with severe frontal dysfunction (frontotemporal dementia, n = 18, and the Richardson form of progressive supranuclear palsy, n = 21) or with medial temporal pathology (amnestic mild cognitive impairment or Alzheimer's disease, n = 14) and healthy participants (n = 18) were given the Verbal Concept Formation Task and a large battery of neuropsychological tests. In addition, all participants underwent 3D T1-weighted MRI to analyse grey matter volume using voxel-based morphometry. Frontal patients were significantly impaired on the Verbal Concept Formation Task as compared to non-frontal participants (P = 0.00001). Global performance score was positively correlated with scores in cognitive tasks assessing executive functions and with grey matter volume in several areas, mostly

  15. Competitive (AP7) and non-competitive (MK-801) NMDA receptor antagonists differentially alter glucose utilization in rat cortex

    SciTech Connect

    Clow, D.W.; Lee, S.J.; Hammer, R.P. Jr. )

    1991-04-01

    The effects of D,L-2-amino-7-phosphonoheptanoic acid (AP7), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, and MK-801, a non-competitive NMDA receptor antagonist, on regional brain metabolism were studied in unanesthetized, freely moving rats by using the quantitative {sup 14}C2-deoxyglucose autoradiographic procedure. AP7 (338 or 901 mg/kg) produced a dose-dependent decrease of metabolic activity throughout most of the regions studied including sensory, motor, and limbic cortices. In contrast, MK-801 (0.1 or 1.0 mg/kg) resulted in a dose-dependent decrease of metabolic activity in sensory cortices, and an increase in limbic regions such as the hippocampal stratum lacunosum moleculare and entorhinal cortex. MK-801 also produced a biphasic response in agranular motor cortex, whereby the low dose increased while the high dose decreased labeling. In addition, MK-801 produced heterogeneous effects on regional cerebral metabolism in sensory cortices. Metabolic activity decreased in layer IV relative to layer Va following MK-801 treatment in primary somatosensory (SI) and visual (VI) cortices, suggesting a shift in activity from afferent fibers innervating layer IV to those innervating layer Va. MK-801 administration also decreased metabolic activity in granular SI relative to dysgranular SI, and in VI relative to secondary visual cortex (VII), thus providing a relative sparing of activity in dysgranular SI and VII. Thus, the non-competitive NMDA receptor antagonist suppressed activity from extrinsic neocortical sources, enhancing relative intracortical activity and stimulating limbic regions, while the competitive NMDA antagonist depressed metabolic activity in all cortical regions.

  16. Surface Layer Turbulence During a Frontal Passage

    SciTech Connect

    Piper, M; Lundquist, J K

    2004-06-15

    Some recent investigations have begun to quantify turbulence and dissipation in frontal zones to address the question of what physical mechanism counteracts the intensification of temperature and velocity gradients across a developing front. Frank (1994) examines the turbulence structure of two fronts that passed a 200m instrumented tower near Karlsruhe, Germany. In addition to showing the mean vertical structure of the fronts as they pass the tower, Frank demonstrates that there is an order of magnitude or more increase in turbulent kinetic energy across the frontal zone. Blumen and Piper (1999) reported turbulence statistics, including dissipation rate measurements, from the MICROFRONTS field experiment, where high-frequency turbulence data were collected from tower-mounted hotwire and sonic anemometers in a cold front and in a density current. Chapman and Browning (2001) measured dissipation rate in a precipitating frontal zone with high-resolution Doppler radar. Their measurements were conducted above the surface layer, to heights of 5km. The dissipation rate values they found are comparable to those measured in Kennedy and Shapiro (1975) in an upper-level front. Here, we expand on these recent studies by depicting the behavior of the fine scales of turbulence near the surface in a frontal zone. The primary objective of this study is to quantify the levels of turbulence and dissipation occurring in a frontal zone through the calculation of kinetic energy spectra and dissipation rates. The high-resolution turbulence data used in this study are taken during the cold front that passed the MICROFRONTS site in the early evening hours of 20 March 1995. These new measurements can be used as a basis for parameterizing the effects of surface-layer turbulence in numerical models of frontogenesis. We present three techniques for calculating the dissipation rate: direct dissipation technique, inertial dissipation technique and Kolmogorov's four-fifths law. Dissipation rate

  17. Selective Long-term Reorganization of the Corticospinal Projection from the Supplementary Motor Cortex following Recovery from Lateral Motor Cortex Injury

    PubMed Central

    McNeal, David W.; Darling, Warren G.; Ge, Jizhi; Stilwell-Morecraft, Kimberly S.; Solon, Kathryn M.; Hynes, Stephanie M.; Pizzimenti, Marc A.; Rotella, Diane; Vanadurongvan, Tyler; Morecraft, Robert J.

    2013-01-01

    Brain injury affecting the frontal motor cortex or its descending axons often causes contralateral upper extremity paresis. Although recovery is variable, the underlying mechanisms supporting favorable motor recovery remain unclear. Since the medial wall of the cerebral hemisphere is often spared following brain injury and recent functional neuroimaging studies in patients indicate a potential role for this brain region in the recovery process, we investigated the long-term effects of isolated lateral frontal motor cortical injury on the corticospinal projection (CSP) from intact, ipsilesional supplementary motor cortex (M2). Following injury to the arm region of the primary motor (M1) and lateral premotor (LPMC) cortices, upper extremity recovery is accompanied by terminal axon plasticity in the contralateral CSP but not the ipsilateral CSP from M2. Furthermore, significant contralateral plasticity occurs only in lamina VII and dorsally within lamina IX. Thus, selective intraspinal sprouting transpires in regions containing interneurons, flexor-related motor neurons and motor neurons supplying intrinsic hand muscles which all play important roles in mediating reaching and digit movements. Following recovery, subsequent injury of M2 leads to reemergence of hand motor deficits. Considering the importance of the CSP in humans and the common occurrence of lateral frontal cortex injury, these findings suggest that spared supplementary motor cortex may serve as an important therapeutic target that should be considered when designing acute and long-term post-injury patient intervention strategies aimed to enhance the motor recovery process following lateral cortical trauma. PMID:20034062

  18. Specific marker of feigned memory impairment: The activation of left superior frontal gyrus.

    PubMed

    Chen, Zi-Xiang; Xue, Li; Liang, Chun-Yu; Wang, Li-Li; Mei, Wei; Zhang, Qiang; Zhao, Hu

    2015-11-01

    Faking memory impairment means normal people complain lots of memory problems without organic damage in forensic assessments. Using alternative forced-choice paradigm, containing digital or autobiographical information, previous neuroimaging studies have indicated that faking memory impairment could cause the activation in the prefrontal and parietal regions, and might involve a fronto-parietal-subcortical circuit. However, it is still unclear whether different memory types have influence on faking or not. Since different memory types, such as long-term memory (LTM) and short-term memory (STM), were found supported by different brain areas, we hypothesized that feigned STM or LTM impairment had distinct neural activation mapping. Besides that, some common neural correlates may act as the general characteristic of feigned memory impairment. To verify this hypothesis, the functional magnetic resonance imaging (fMRI) combined with an alternative word forced-choice paradigm were used in this study. A total of 10 right-handed participants, in this study, had to perform both STW and LTM tasks respectively under answering correctly, answering randomly and feigned memory impairment conditions. Our results indicated that the activation of the left superior frontal gyrus and the left medial frontal gyrus was associated with feigned LTM impairment, whereas the left superior frontal gyrus, the left precuneus and the right anterior cingulate cortex (ACC) were highly activated while feigning STM impairment. Furthermore, an overlapping was found in the left superior frontal gyrus, and it suggested that the activity of the left superior frontal gyrus might be acting as a specific marker of feigned memory impairment. PMID:26479324

  19. Attention enhances multi-voxel representation of novel objects in frontal, parietal and visual cortices.

    PubMed

    Woolgar, Alexandra; Williams, Mark A; Rich, Anina N

    2015-04-01

    Selective attention is fundamental for human activity, but the details of its neural implementation remain elusive. One influential theory, the adaptive coding hypothesis (Duncan, 2001, An adaptive coding model of neural function in prefrontal cortex, Nature Reviews Neuroscience 2:820-829), proposes that single neurons in certain frontal and parietal regions dynamically adjust their responses to selectively encode relevant information. This selective representation may in turn support selective processing in more specialized brain regions such as the visual cortices. Here, we use multi-voxel decoding of functional magnetic resonance images to demonstrate selective representation of attended--and not distractor--objects in frontal, parietal, and visual cortices. In addition, we highlight a critical role for task demands in determining which brain regions exhibit selective coding. Strikingly, representation of attended objects in frontoparietal cortex was highest under conditions of high perceptual demand, when stimuli were hard to perceive and coding in early visual cortex was weak. Coding in early visual cortex varied as a function of attention and perceptual demand, while coding in higher visual areas was sensitive to the allocation of attention but robust to changes in perceptual difficulty. Consistent with high-profile reports, peripherally presented objects could also be decoded from activity at the occipital pole, a region which corresponds to the fovea. Our results emphasize the flexibility of frontoparietal and visual systems. They support the hypothesis that attention enhances the multi-voxel representation of information in the brain, and suggest that the engagement of this attentional mechanism depends critically on current task demands. PMID:25583612

  20. Selective Thalamic Innervation of Rat Frontal Cortical Neurons.

    PubMed

    Shigematsu, Naoki; Ueta, Yoshifumi; Mohamed, Alsayed A; Hatada, Sayuri; Fukuda, Takaichi; Kubota, Yoshiyuki; Kawaguchi, Yasuo

    2016-06-01

    Most glutamatergic inputs in the neocortex originate from the thalamus or neocortical pyramidal cells. To test whether thalamocortical afferents selectively innervate specific cortical cell subtypes and surface domains, we investigated the distribution patterns of thalamocortical and corticocortical excitatory synaptic inputs in identified postsynaptic cortical cell subtypes using intracellular and immunohistochemical staining combined with confocal laser scanning and electron microscopic observations in 2 thalamorecipient sublayers, lower layer 2/3 (L2/3b) and lower layer 5 (L5b) of rat frontal cortex. The dendrites of GABAergic parvalbumin (PV) cells preferentially received corticocortical inputs in both sublayers. The somata of L2/3b PV cells received thalamic inputs in similar proportions to the basal dendritic spines of L2/3b pyramidal cells, whereas L5b PV somata were mostly innervated by cortical inputs. The basal dendrites of L2/3b pyramidal and L5b corticopontine pyramidal cells received cortical and thalamic glutamatergic inputs in proportion to their local abundance, whereas crossed-corticostriatal pyramidal cells in L5b exhibited a preference for thalamic inputs, particularly in their distal dendrites. Our data demonstrate an exquisite selectivity among thalamocortical afferents in which synaptic connectivity is dependent on the postsynaptic neuron subtype, cortical sublayer, and cell surface domain. PMID:26045568

  1. Successive bilateral frontal controlled cortical impact injuries show behavioral savings.

    PubMed

    Vonder Haar, Cole; Friend, Danielle M; Mudd, David B; Smith, Jeffrey S

    2013-03-01

    Traumatic brain injuries (TBIs) affect millions of people each year. Research investigating repeated or serial damage in the form of lesions indicates that behavioral deficits are reduced in animals given sequential lesions separated by a sufficient period of recovery. In the lesion literature, this phenomenon is known as the serial lesion effect (SLE). Although the SLE phenomenon is established in the lesion literature, it has not been thoroughly investigated under current models of brain injury. In the current study, a controlled cortical impact of the bilateral frontal cortex was performed in either a single procedure or a serial procedure separated by two weeks. Rats were tested on the Morris water maze, bilateral tactile adhesive removal task, rotarod and Barnes maze task to determine behavioral deficits. Histology was performed to determine lesion size and astrocyte and microglial response. A serial lesion effect was demonstrated across a majority of the behavioral tasks. However, histological analyses did not suggest a clear mechanistic link to the behavioral phenomena. This is the first study to demonstrate the SLE in a model of TBI, suggesting that behavioral deficits may actually be reduced in repeated head injuries, given an adequate time window between injuries. PMID:23201357

  2. Delayed synchronization of activity in cortex and subthalamic nucleus following cortical stimulation in the rat

    PubMed Central

    Magill, Peter J; Sharott, Andrew; Bolam, J Paul; Brown, Peter

    2006-01-01

    Oscillations may play a role in the functional organization of cortico-basal ganglia-thalamocortical circuits, and it is important to understand their underlying mechanisms. The cortex often drives basal ganglia (BG) activity, and particularly, oscillatory activity in the subthalamic nucleus (STN). However, the STN may also indirectly influence cortex. The aim of this study was to characterize the delayed (>200 ms) responses of STN neurons to synchronized cortical inputs, focusing on their relationship with oscillatory cortical activity. We recorded the short-latency and delayed responses of STN units and frontal electrocorticogram (ECoG) to cortical stimulation in anaesthetized rats. Similar to previous studies, stimulation of ipsilateral frontal cortex, but not temporal cortex, evoked a short-latency triphasic response, followed by a sustained reduction or pause in firing, in rostral STN units. Caudal STN units did not show the short-latency triphasic response but often displayed a prolonged firing reduction. Oscillations in STN unit activity and ECoG were common after this sustained firing reduction, particularly between 200 and 600 ms after frontal cortical stimulation. These delayed oscillations were significantly coherent in a broad frequency band of 5–30 Hz. Coherence with ECoG at 5–15 Hz was observed throughout STN, though coherence at 15–30 Hz was largely restricted to rostral STN. Furthermore, oscillatory responses at 5–30 Hz in rostral STN predominantly led those in cortex (mean latency of 29 ms) after frontal cortical stimulation. These findings suggest that STN neurons responding to corticosubthalamic inputs may provide a delayed input to cortex, via BG output nuclei, and thence, thalamocortical pathways. PMID:16709634

  3. Preservation of Frontal Sinus Anatomy and Outflow Tract Following Frontal Trauma with Dural Defect

    PubMed Central

    Chin, David Chao Wu; Loh, Ian Chi Yuan

    2015-01-01

    Summary: Our case report describes a young male mechanic who was hit in his face by a spring while repairing a car, resulting in traumatic injury to the frontal sinus, with fractures of both the anterior and the posterior tables with dural defect and cerebrospinal fluid leak. Current guidelines recommend that comminuted and/or displaced fractures of the posterior table of the frontal sinus with dural defects should be either cranialized or obliterated. In this patient, instead of cranializing or obliterating the frontal sinus, we managed to preserve the frontal sinus anatomy and its outflow tract using a combined open bicoronal and nasoendoscopic approach. This avoids the long-term complications associated with cranialization or obliteration including mucocele formation and frontocutaneous fistula. PMID:25750839

  4. Spatial Organization of Direct Hippocampal Field CA1 Axonal Projections To the Rest of the Cerebral Cortex

    PubMed Central

    CENQUIZCA, LEE A.; SWANSON, LARRY W.

    2007-01-01

    The spatial distribution of axonal projections descending from rat field CA1 to thalamus and hypothalamus was analyzed previously with the PHAL method (Cenquizca and Swanson, 2006). The same experimental material was used here to define the topography of field CA1 association projections to other cerebral cortical areas. First, the results confirm and extend known intrahippocampal formation inputs to dentate gyrus, subiculum, presubiculum, parasubiculum, and entorhinal area, which are arranged generally along the formation’s transverse axis and dominated by the subicular projection—by far the densest established by field CA1 anywhere in the brain. And second, field CA1 innervates a virtually complete ring of extrahippocampal formation cortex via three routes. A dorsal pathway from the dorsal third of field CA1 innervates moderately the retrosplenial area; a moderately strong ventral pathway from the ventral two-thirds of field CA1 passing through the longitudinal association bundle sends offshoots to visual, auditory, somatosensory, gustatory, main and accessory olfactory, and visceral areas—as well as the basolateral amygdalar complex and the agranular insular and orbital areas; and a cortical-subcortical-cortical pathway through the fornix from the whole longitudinal extent of field CA1 innervates rather strongly a rostral region that includes the tenia tecta along with the anterior cingulate, prelimbic, infralimbic, and orbital areas. The functional consequences of long-term potentiation in field CA1 projection neurons remain to be explored. PMID:17559940

  5. Disgust trait modulates frontal-posterior coupling as a function of disgust domain

    PubMed Central

    de Jong, Peter J.; Renken, Remco J.; Georgiadis, Janniko R.

    2013-01-01

    Following the two-stage model of disgust, ‘core disgust’ (e.g. elicited by rotten food) is extended to stimuli that remind us of our animal nature ‘AR disgust’ (e.g. mutilations, animalistic instincts). There is ample evidence that core and AR represent distinct domains of disgust elicitors. Moreover, people show large differences in their tendency to respond with disgust to potential disgust elicitors (propensity), as well as in their appraisal of experiencing disgust (sensitivity). Thus these traits may be important moderators of people's response patterns. Here, we aimed to find brain mechanisms associated with these distinct disgust domains and traits, as well as the interaction between them. The right ventrolateral occipitotemporal cortex, which preferentially responded to visual AR, was functionally coupled to the middle cingulate cortex (MCC), thalamus and prefrontal cortex (medial, dorsolateral), as a function of disgust domain. Coupling with the anterior part of MCC was modulated by disgust ‘propensity’, which was strongest during AR. Coupling with anterior insula and ventral premotor cortex was weaker, but relied fully on this domain–trait interaction. Disgust ‘sensitivity’ modulated left anterior insula activity irrespective of domain, and did not affect functional connectivity. Thus a frontal-posterior network that interacts with disgust ‘propensity’ dissects AR and core disgust. PMID:22258801

  6. The evolution of the frontal lobes: a volumetric analysis based on three-dimensional reconstructions of magnetic resonance scans of human and ape brains.

    PubMed

    Semendeferi, K; Damasio, H; Frank, R; Van Hoesen, G W

    1997-04-01

    Scenarios regarding the evolution of cognitive function in hominids depend largely on our understanding of the organization of the frontal lobes in extant humans and apes. The frontal lobe is involved in functions such as creative thinking, planning of future actions, decision making, artistic expression, aspects of emotional behavior, as well as working memory, language and motor control. It is often claimed that the frontal lobe is disproportionately larger in humans than in other species, but conflicting reports exist on this issue. The brain of the apes in particular remains largely unknown. In this report we measure the volume of the frontal lobe as a whole and of its main sectors (including cortex and immediately underlying white matter) in living humans, and in post-mortem brains of the chimpanzee, gorilla, orang-utan, gibbon and the macaque using three-dimensional reconstructions of magnetic resonance (MR) scans of the brain. On the basis of these data we suggest that although the absolute volume of the brain and the frontal lobe is largest in humans, the relative size of the frontal lobe is similar across hominoids, and that humans do not have a larger frontal lobe than expected from a primate brain of the human size. We also report that the relative size of the sectors of the frontal lobe (dorsal, mesial, orbital) is similar across the primate species studied. Our conclusions are preliminary, because the size of our sample, although larger than in previous studies, still remains small. With this caveat we conclude that the overall volume of the frontal lobe in hominids enlarged in absolute size along with the rest of the brain, but did not become relatively larger after the split of the human line from the ancestral African hominoid stock. Aspects other than relative volume of the frontal lobe have to be responsible for the cognitive specializations of the hominids. PMID:9085187

  7. Deficits in prospective memory following damage to the prefrontal cortex.

    PubMed

    Umeda, Satoshi; Kurosaki, Yoshiko; Terasawa, Yuri; Kato, Motoichiro; Miyahara, Yasuyuki

    2011-07-01

    Neuropsychological investigations of prospective memory (PM), representing memory of future intentions or plans, have evolved over the past two decades. The broadly accepted divisions involved in PM consist of a prospective memory component (PMC), a process for remembering to remember, and a retrospective memory component, a process for remembering the content of the intended action. Previous functional neuroimaging studies have provided some evidence that the rostral prefrontal cortex (BA10) is one of areas that is critical for prospective remembering. However, the question of whether damage to part of the prefrontal cortex affects attenuated performance for PMC remains unresolved. In this study, 74 participants with traumatic brain injury (TBI) including focal damage to frontal or temporal lobe areas were administered thirteen standard neuropsychological tests and the PM task. To identify influential areas contributing to PM performance, discriminant function analysis was conducted. The results indicated that the following three areas are highly contributory to PM performance: the right dorsolateral prefrontal cortex; the right ventromedial prefrontal cortex; and the left dorsomedial prefrontal cortex. Comparing differences in neuropsychological test scores showed that orientation scores were significantly higher in the greater PM performance group, suggesting that PMC represents an integrated memory function associated with awareness of current status. These data contribute to our understanding of the neural substrates and functional characteristics of the PMC. PMID:21477605

  8. Criminal Responsibility of the Frontal Lobe Syndrome

    PubMed Central

    Sener, Mustafa Talip; Ozcan, Halil; Sahingoz, Sadik; Ogul4, Hayri

    2015-01-01

    Neurological and/or psychiatric symptoms might be detected due to damage of frontal lobes as detected in damages of many brain regions. Frontal lobe syndrome (FLS) occurs as a result of damage in prefrontal region due to various causes. Symptoms due to prefrontal region damage, varies according to the size and location of the lesion. In most of the cases; executive dysfunctions, attention deficits, inconsistencies in social life, impulse control problems, obsessive behaviors and violence behaviors are common clinical signs. Behavioral symptoms seen in FLS can be confused with personality disorders and negative symptoms of schizophrenia. FLS is a neuropsychiatric disorder rarely assessed in forensic psychiatry and in terms of detection of criminal responsibility. In this case report, criminal responsibility in FLS was assessed through a FLS case in which an offense of “threat” was committed and investigated in terms of criminal responsibility. PMID:26644774

  9. Criminal Responsibility of the Frontal Lobe Syndrome.

    PubMed

    Sener, Mustafa Talip; Ozcan, Halil; Sahingoz, Sadik; Ogul, Hayri

    2015-10-01

    Neurological and/or psychiatric symptoms might be detected due to damage of frontal lobes as detected in damages of many brain regions. Frontal lobe syndrome (FLS) occurs as a result of damage in prefrontal region due to various causes. Symptoms due to prefrontal region damage, varies according to the size and location of the lesion. In most of the cases; executive dysfunctions, attention deficits, inconsistencies in social life, impulse control problems, obsessive behaviors and violence behaviors are common clinical signs. Behavioral symptoms seen in FLS can be confused with personality disorders and negative symptoms of schizophrenia. FLS is a neuropsychiatric disorder rarely assessed in forensic psychiatry and in terms of detection of criminal responsibility. In this case report, criminal responsibility in FLS was assessed through a FLS case in which an offense of "threat" was committed and investigated in terms of criminal responsibility. PMID:26644774

  10. "No Longer Gage": Frontal Lobe Dysfunction and Emotional Changes.

    ERIC Educational Resources Information Center

    Stuss, Donald T.; And Others

    1992-01-01

    Reviews changes in emotional response and personality occurring after damage to frontal systems, proposes operational definitions, and analyzes reports according to these definitions. Summarizes neurological causes of frontal lobe damage and associations of frontal dysfunction with psychiatric disturbances. Proposes that primary change after…

  11. Material-dependent and material-independent selection processes in the frontal and parietal lobes: an event-related fMRI investigation of response competition

    NASA Technical Reports Server (NTRS)

    Hazeltine, Eliot; Bunge, Silvia A.; Scanlon, Michael D.; Gabrieli, John D E.

    2003-01-01

    The present study used the flanker task [Percept. Psychophys. 16 (1974) 143] to identify neural structures that support response selection processes, and to determine which of these structures respond differently depending on the type of stimulus material associated with the response. Participants performed two versions of the flanker task while undergoing event-related functional magnetic resonance imaging (fMRI). Both versions of the task required participants to respond to a central stimulus regardless of the responses associated with simultaneously presented flanking stimuli, but one used colored circle stimuli and the other used letter stimuli. Competition-related activation was identified by comparing Incongruent trials, in which the flanker stimuli indicated a different response than the central stimulus, to Neutral stimuli, in which the flanker stimuli indicated no response. A region within the right inferior frontal gyrus exhibited significantly more competition-related activation for the color stimuli, whereas regions within the middle frontal gyri of both hemispheres exhibited more competition-related activation for the letter stimuli. The border of the right middle frontal and inferior frontal gyri and the anterior cingulate cortex (ACC) were significantly activated by competition for both types of stimulus materials. Posterior foci demonstrated a similar pattern: left inferior parietal cortex showed greater competition-related activation for the letters, whereas right parietal cortex was significantly activated by competition for both materials. These findings indicate that the resolution of response competition invokes both material-dependent and material-independent processes.

  12. Frontal lobe astrocytoma following radiotherapy for medulloblastoma

    SciTech Connect

    Cohen, M.S.; Kushner, M.J.; Dell, S.

    1981-05-01

    A young woman had a frontal lobe astrocytoma 14 years after successful treatment of a posterior fossa medulloblastoma by surgery and whole-neuraxis irradiation. The association of these two tumors is rare, and it is unlikely that the second tumor was the result of metastasis and differentiation of residual or recurrent medulloblastoma. We review the evidence supporting this view and also the likelihood that the astrocytoma was induced by the prior radiation.

  13. Frontal Sinus Fractures: A Conservative Shift

    PubMed Central

    Weathers, William M.; Wolfswinkel, Erik M.; Hatef, Daniel A.; Lee, Edward I.; Brown, Rodger H.; Hollier, Larry H.

    2013-01-01

    This article reflects on the changing management of frontal sinus fractures. Severity of these injuries has decreased tremendously since the universal adoption of seat belts and air bags. Recently, there has been a shift from aggressive surgical management to more conservative management strategies, some forgoing surgery all together. New technologies, such as bioabsorbable plates and endoscopic sinus surgery, are leading the way in improved surgical management strategies and offer promising alternatives to the more traditional approaches. PMID:24436753

  14. Cervical spine response in frontal crash.

    PubMed

    Panzer, Matthew B; Fice, Jason B; Cronin, Duane S

    2011-11-01

    Predicting neck response and injury resulting from motor vehicle accidents is essential to improving occupant protection. A detailed human cervical spine finite element model has been developed, with material properties and geometry determined a priori of any validation, for the evaluation of global kinematics and tissue-level response. Model validation was based on flexion/extension response at the segment level, tension response of the whole ligamentous cervical spine, head kinematic response from volunteer frontal impacts, and soft tissue response from cadaveric whole cervical spine frontal impacts. The validation responses were rated as 0.79, assessed using advanced cross-correlation analysis, indicating the model exhibits good biofidelity. The model was then used to evaluate soft tissue response in frontal impact scenarios ranging from 8G to 22G in severity. Disc strains were highest in the C4-C5-C6 segments, and ligament strains were greatest in the ISL and LF ligaments. Both ligament and disc fiber strain levels exceeded the failure tolerances in the 22G case, in agreement with existing data. This study demonstrated that a cervical spine model can be developed at the tissue level and provide accurate biofidelic kinematic and local tissue response, leading to injury prediction in automotive crash scenarios. PMID:21665513

  15. Frontal lobe function in temporal lobe epilepsy

    PubMed Central

    Stretton, J.; Thompson, P.J.

    2012-01-01

    Summary Temporal lobe epilepsy (TLE) is typically associated with long-term memory dysfunction. The frontal lobes support high-level cognition comprising executive skills and working memory that is vital for daily life functioning. Deficits in these functions have been increasingly reported in TLE. Evidence from both the neuropsychological and neuroimaging literature suggests both executive function and working memory are compromised in the presence of TLE. In relation to executive impairment, particular focus has been paid to set shifting as measured by the Wisconsin Card Sorting Task. Other discrete executive functions such as decision-making and theory of mind also appear vulnerable but have received little attention. With regard to working memory, the medial temporal lobe structures appear have a more critical role, but with emerging evidence of hippocampal dependent and independent processes. The relative role of underlying pathology and seizure spread is likely to have considerable bearing upon the cognitive phenotype and trajectory in TLE. The identification of the nature of frontal lobe dysfunction in TLE thus has important clinical implications for prognosis and surgical management. Longitudinal neuropsychological and neuroimaging studies assessing frontal lobe function in TLE patients pre- and postoperatively will improve our understanding further. PMID:22100147

  16. Methamphetamine blocks exercise effects on Bdnf and Drd2 gene expression in frontal cortex and striatum.

    PubMed

    Thompson, Andrew B; Stolyarova, Alexandra; Ying, Zhe; Zhuang, Yumei; Gómez-Pinilla, Fernando; Izquierdo, Alicia

    2015-12-01

    Exposure to drugs of abuse can produce many neurobiological changes which may lead to increased valuation of rewards and decreased sensitivity to their costs. Many of these behavioral alterations are associated with activity of D2-expressing medium spiny neurons in the striatum. Additionally, Bdnf in the striatum has been shown to play a role in flexible reward-seeking behavior. Given that voluntary aerobic exercise can affect the expression of these proteins in healthy subjects, and that exercise has shown promise as an anti-addictive therapy, we set out to quantify changes in D2 and Bdnf expression in methamphetamine-exposed rats given access to running wheels. Sixty-four rats were treated for two weeks with an escalating dose of methamphetamine or saline, then either sacrificed, housed in standard cages, or given free access to a running wheel for 6 weeks prior to sacrifice. Rats treated with methamphetamine ran significantly greater distances than saline-treated rats, suggesting an augmentation in the reinforcement value of voluntary wheel running. Transcription of Drd2 and Bdnf was assessed via RT-qPCR. Protein expression levels of D2 and phosphorylation of the TrkB receptor were measured via western blot. Drd2 and Bdnf mRNA levels were impacted independently by exercise and methamphetamine, but exposure to methamphetamine prior to the initiation of exercise blocked the exercise-induced changes seen in rats treated with saline. Expression levels of both proteins were elevated immediately after methamphetamine, but returned to baseline after six weeks, regardless of exercise status. PMID:26334786

  17. Functional Connectivity Separates Switching Operations in the Posterior Lateral Frontal Cortex

    ERIC Educational Resources Information Center

    Stelzel, Christine; Basten, Ulrike; Fiebach, Christian J.

    2011-01-01

    Task representations consist of different aspects such as the representations of the relevant stimuli, the abstract rules to be applied, and the actions to be performed. To be flexible in our daily lives, we frequently need to switch between some or all aspects of a task. In the present study, we examined whether switching between abstract task…

  18. A Computational Model of Inhibitory Control in Frontal Cortex and Basal Ganglia

    ERIC Educational Resources Information Center

    Wiecki, Thomas V.; Frank, Michael J.

    2013-01-01

    Planning and executing volitional actions in the face of conflicting habitual responses is a critical aspect of human behavior. At the core of the interplay between these 2 control systems lies an override mechanism that can suppress the habitual action selection process and allow executive control to take over. Here, we construct a neural circuit…

  19. How Left Inferior Frontal Cortex Participates in Syntactic Processing: Evidence from Aphasia

    ERIC Educational Resources Information Center

    Love, Tracy; Swinney, David; Walenski, Matthew; Zurif, Edgar

    2008-01-01

    We report on three experiments that provide a real-time processing perspective on the poor comprehension of Broca's aphasic patients for non-canonically structured sentences. In the first experiment we presented sentences (via a Cross Modal Lexical Priming (CMLP) paradigm) to Broca's patients at a normal rate of speech. Unlike the pattern found…

  20. Target Selection by the Frontal Cortex during Coordinated Saccadic and Smooth Pursuit Eye Movements

    ERIC Educational Resources Information Center

    Srihasam, Krishna; Bullock, Daniel; Grossberg, Stephen

    2009-01-01

    Oculomotor tracking of moving objects is an important component of visually based cognition and planning. Such tracking is achieved by a combination of saccades and smooth-pursuit eye movements. In particular, the saccadic and smooth-pursuit systems interact to often choose the same target, and to maximize its visibility through time. How do…

  1. Orbito-frontal cortex and thalamus volumes in obsessive-compulsive disorder before and after pharmacotherapy.

    PubMed

    Atmaca, Murad; Mermi, Osman; Yildirim, Hanefi; Gurok, M Gurkan

    2016-09-01

    In the present study, we focused on the key brain regions, OFC and thalamus, to investigate the roles of antiobsessional agents on volume changes of these brain regions after 12 weeks of anti-obsessional treatment in patients with obsessive-compulsive disorder (OCD). Fourteen patients with OCD and the same number of healthy controls were included in the study. At baseline, the volumes of the OFC and thalamus were compared by using magnetic resonance imaging (MRI) between groups. The volumes of OFC and thalamus were evaluated before and after the anti-obsessional drug treatment solely in the patient group. Our study revealed that thalamus volumes were reduced statistically significantly throughout the treatment period. However, we found that OFC volumes did not change statistically significantly throughout the treatment period. In summary, our study found that anti-obsessional drug treatment had an effect on thalamus volumes throughout the treatment period for both sides but not on OFC volumes. However, future studies with larger sample are required. PMID:26311393

  2. The Involvement of Occipital and Inferior Frontal Cortex in the Phonological Learning of Chinese Characters

    ERIC Educational Resources Information Center

    Deng, Yuan; Chou, Tai-li; Ding, Guo-sheng; Peng, Dan-ling; Booth, James R.

    2011-01-01

    Neural changes related to the learning of the pronunciation of Chinese characters in English speakers were examined using fMRI. We examined the item-specific learning effects for trained characters and the generalization of phonetic knowledge to novel transfer characters that shared a phonetic radical (part of a character that gives a clue to the…

  3. Medial frontal cortex motivates but does not control movement initiation in the countermanding task.

    PubMed

    Scangos, Katherine Wilson; Stuphorn, Veit

    2010-02-01

    Voluntary control of behavior implies the ability to select what action is performed. The supplementary motor area (SMA) and pre-SMA are widely considered to be of central importance for this ability because of their role in movement initiation and inhibition. To test this hypothesis, we recorded from neurons in SMA and pre-SMA of monkeys performing an arm countermanding task. Temporal analysis of neural activity and behavior in this task allowed us to test whether neural activity is sufficient to control movement initiation or inhibition. Surprisingly, 99% (242 of 243) of movement-related neurons in SMA and pre-SMA failed to exhibit time-locked activity changes predictive of movement initiation in this task. We also found a second group of neurons that was more active during successful response cancelation. Of these putative inhibitory cells, 18% (7 of 40) responded early enough to be able to influence the cancelation of the movement. Thus, when tested with the countermanding task, the SMA/pre-SMA region may play a role in movement inhibition but does not appear to control movement initiation. However, the activity of 76% (202 of 267) of movement-related neurons was contingent on the expectation of reward and 42% of them reflected the amount of expected reward. These findings suggest that the movement-related activity in pre-SMA and SMA might represent the motivation for a specific action but does not determine whether or not that action is performed. This motivational signal in pre-SMA and SMA could provide an essential link between reward expectation and motor execution. PMID:20130204

  4. The Impact of Frontal and Non-Frontal Brain Tumor Lesions on Wisconsin Card Sorting Test Performance

    ERIC Educational Resources Information Center

    Goldstein, B.; Obrzut, J. E.; John, C.; Ledakis, G.; Armstrong, C. L.

    2004-01-01

    Several lesion and imaging studies have suggested that the Wisconsin Card Sorting Test (WCST) is a measure of executive dysfunction. However, some studies have reported that this measure has poor anatomical specificity because patients with either frontal or non-frontal focal lesions exhibit similar performance. This study examined 25 frontal, 20…

  5. Frontal osteomyelitis presenting as upper eyelid ectropion: A cautionary tale

    PubMed Central

    Bandyopadhyay, Rakhi; Chatterjee, Arkendu; Banerjee, Sambit; Bandyopadhyay, Samir Kumar; Mondol, Anup

    2015-01-01

    Frontal osteomyelitis is a rare clinical entity that can occur as sequelae to frontal sinusitis, head trauma, as a postoperative complication following sinus surgery or due to haematogenous spread. It usually presents with a soft, fluctuant forehead swelling with pain and fever. Cicatricial ectropion is an extremely rare feature of frontal osteomyelitis. We present a young male patient presenting with cicatricial ectropion that occurred as the sole manifestation of an underlying frontal osteomyelitis. Extensive Medline search did not find any such reported case. We feel that frontal osteomyelitis should be kept in mind as a possible etiology when considering the differential diagnosis of cicatricial ectropion. PMID:26155088

  6. The Prefrontal Cortex Achieves Inhibitory Control by Facilitating Subcortical Motor Pathway Connectivity

    PubMed Central

    Hughes, Laura E.; Anderson, Michael C.; Rowe, James B.

    2015-01-01

    Communication between the prefrontal cortex and subcortical nuclei underpins the control and inhibition of behavior. However, the interactions in such pathways remain controversial. Using a stop-signal response inhibition task and functional imaging with analysis of effective connectivity, we show that the lateral prefrontal cortex influences the strength of communication between regions in the frontostriatal motor system. We compared 20 generative models that represented alternative interactions between the inferior frontal gyrus, presupplementary motor area (preSMA), subthalamic nucleus (STN), and primary motor cortex during response inhibition. Bayesian model selection revealed that during successful response inhibition, the inferior frontal gyrus modulates an excitatory influence of the preSMA on the STN, thereby amplifying the downstream polysynaptic inhibition from the STN to the motor cortex. Critically, the strength of the interaction between preSMA and STN, and the degree of modulation by the inferior frontal gyrus, predicted individual differences in participants' stopping performance (stop-signal reaction time). We then used diffusion-weighted imaging with tractography to assess white matter structure in the pathways connecting these three regions. The mean diffusivity in tracts between preSMA and the STN, and between the inferior frontal gyrus and STN, also predicted individual differences in stopping efficiency. Finally, we found that white matter structure in the tract between preSMA and STN correlated with effective connectivity of the same pathway, providing important cross-modal validation of the effective connectivity measures. Together, the results demonstrate the network dynamics and modulatory role of the prefrontal cortex that underpin individual differences in inhibitory control. PMID:25589771

  7. Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia

    PubMed Central

    Honey, Garry D.; Bullmore, Edward T.; Soni, William; Varatheesan, Malini; Williams, Steve C. R.; Sharma, Tonmoy

    1999-01-01

    Antipsychotic drug treatment of schizophrenia may be complicated by side effects of widespread dopaminergic antagonism, including exacerbation of negative and cognitive symptoms due to frontal cortical hypodopaminergia. Atypical antipsychotics have been shown to enhance frontal dopaminergic activity in animal models. We predicted that substitution of risperidone for typical antipsychotic drugs in the treatment of schizophrenia would be associated with enhanced functional activation of frontal cortex. We measured cerebral blood oxygenation changes during periodic performance of a verbal working memory task, using functional MRI, on two occasions (baseline and 6 weeks later) in two cohorts of schizophrenic patients. One cohort (n = 10) was treated with typical antipsychotic drugs throughout the study. Risperidone was substituted for typical antipsychotics after baseline assessment in the second cohort (n = 10). A matched group of healthy volunteers (n = 10) was also studied on a single occasion. A network comprising bilateral dorsolateral prefrontal and lateral premotor cortex, the supplementary motor area, and posterior parietal cortex was activated by working memory task performance in both the patients and comparison subjects. A two-way analysis of covariance was used to estimate the effect of substituting risperidone for typical antipsychotics on power of functional response in the patient group. Substitution of risperidone increased functional activation in right prefrontal cortex, supplementary motor area, and posterior parietal cortex at both voxel and regional levels of analysis. This study provides direct evidence for significantly enhanced frontal function in schizophrenic patients after substitution of risperidone for typical antipsychotic drugs, and it indicates the potential value of functional MRI as a tool for longitudinal assessment of psychopharmacological effects on cerebral physiology. PMID:10557338

  8. Impairments in proverb interpretation following focal frontal lobe lesions.

    PubMed

    Murphy, Patrick; Shallice, Tim; Robinson, Gail; MacPherson, Sarah E; Turner, Martha; Woollett, Katherine; Bozzali, Marco; Cipolotti, Lisa

    2013-09-01

    The proverb interp