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Sample records for fetal frontal cortex

  1. The frontal cortex IGF system is down regulated in the term, intrauterine growth restricted fetal baboon.

    PubMed

    Xie, L; Antonow-Schlorke, I; Schwab, M; McDonald, T J; Nathanielsz, P W; Li, C

    2013-10-01

    The IGF system exerts systemic and local actions during development. We previously demonstrated that fetal cerebral cortical IGF1 is reduced at 0.5 gestation in our IUGR baboon nonhuman primate model. We hypothesized that by term protein expression of several key IGF system stimulatory peptide pathway components and downstream nutrient signaling effectors of IGF, mammalian target of rapamycin (mTOR) and S6, would decrease, indicating reduced cellular nutrient uptake and protein synthesis. We fed 7 control baboons ad libitum while 6 baboons ate a globally reduced diet (70% of feed eaten by controls) from 0.16 gestation through pregnancy that produces IUGR. Fetuses were removed at Cesarean section at 0.9 gestation. Frontal cortex sections were stained for IGFI, IGFII, IGFRI, IGFR2, IGFBP2, 3, 5 and 6, and mTOR and ribosomal protein S6 and double stained with NeuN a neuron-specific nuclear antigen. All proteins stained neuronal cytoplasm except IGFRI which showed only glial cell cytoplasmic and blood vessel staining. IUGR fetuses showed decreased frontal cortical immunoreactive IGFI, IGFII, IGFRI, IGFBP2, 5 and 6, and mTOR and S6 (p < 0.05). IGFBP3 increased (p < 0.05) and IGFR2 was unchanged (p > 0.05). There were no differences between male and female fetal brains. When fetal nutrient availability is decreased, IUGR down regulates the IGF system and its mTOR signaling pathway in the fetal frontal cortex coincident with slowed growth. These findings emphasize the importance of the local tissue IGF system in fetal primate brain development. © 2013.

  2. Fetal frontal cortex transplant (/sup 14/C) 2-deoxyglucose uptake and histology: survival in cavities of host rat brain motor cortex

    SciTech Connect

    Sharp, F.R.; Gonzalez, M.F.

    1984-10-01

    Fetal frontal neocortex from 18-day-old rat embryonic brain was transplanted into cavities in 30-day-old host motor cortex. Sixty days after transplantation, 5 of 15 transplanted rats had surviving fetal transplants. The fetal cortex transplants were physically attached to the host brain, completely filled the original cavity, and had numerous surviving cells including pyramidal neurons. Cell lamination within the fetal transplant was abnormal. The (/sup 14/C) 2-deoxyglucose uptake of all five of the fetal neocortex transplants was less than adjacent cortex and contralateral host motor-sensory cortex, but more than adjacent corpus callosum white matter. The results indicate that fetal frontal neocortex can be transplanted into damaged rat motor cortex. The metabolic rate of the transplants suggests they could be partially functional.

  3. [Neuroanatomy of Frontal Association Cortex].

    PubMed

    Takada, Masahiko

    2016-11-01

    The frontal association cortex is composed of the prefrontal cortex and the motor-related areas except the primary motor cortex (i.e., the so-called higher motor areas), and is well-developed in primates, including humans. The prefrontal cortex receives and integrates large bits of diverse information from the parietal, temporal, and occipital association cortical areas (termed the posterior association cortex), and paralimbic association cortical areas. This information is then transmitted to the primary motor cortex via multiple motor-related areas. Given these facts, it is likely that the prefrontal cortex exerts executive functions for behavioral control. The functional input pathways from the posterior and paralimbic association cortical areas to the prefrontal cortex are classified primarily into six groups. Cognitive signals derived from the prefrontal cortex are conveyed to the rostral motor-related areas to transform them into motor signals, which finally enter the primary motor cortex via the caudal motor-related areas. Furthermore, it has been shown that, similar to the primary motor cortex, areas of the frontal association cortex form individual networks (known as "loop circuits") with the basal ganglia and cerebellum via the thalamus, and hence are extensively involved in the expression and control of behavioral actions.

  4. 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.

  5. Conserved Sequence Processing in Primate Frontal Cortex.

    PubMed

    Wilson, Benjamin; Marslen-Wilson, William D; Petkov, Christopher I

    2017-02-01

    An important aspect of animal perception and cognition is learning to recognize relationships between environmental events that predict others in time, a form of relational knowledge that can be assessed using sequence-learning paradigms. Humans are exquisitely sensitive to sequencing relationships, and their combinatorial capacities, most saliently in the domain of language, are unparalleled. Recent comparative research in human and nonhuman primates has obtained behavioral and neuroimaging evidence for evolutionarily conserved substrates involved in sequence processing. The findings carry implications for the origins of domain-general capacities underlying core language functions in humans. Here, we synthesize this research into a 'ventrodorsal gradient' model, where frontal cortex engagement along this axis depends on sequencing complexity, mapping onto the sequencing capacities of different species. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. 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

  7. 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

  8. 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.

  9. 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

  10. Dementia of frontal lobe type and motor neuron disease. A Golgi study of the frontal cortex.

    PubMed Central

    Ferrer, I; Roig, C; Espino, A; Peiro, G; Matias Guiu, X

    1991-01-01

    Neuropathological findings in a 38 year old patient with dementia of frontal lobe type and motor neuron disease included pyramidal tracts, myelin pallor and neuron loss, gliosis and chromatolysis in the hypoglossal nucleus, together with frontal atrophy, neuron loss, gliosis and spongiosis in the upper cortical layers of the frontal (and temporal) lobes. Most remaining pyramidal and non-pyramidal neurons (multipolar, bitufted and bipolar cells) in the upper layers (layers II and III) of the frontal cortex (area B) had reduced dendritic arbors, proximal dendritic varicosities and amputation of dendrites as revealed in optimally stained rapid Golgi sections. Pyramidal cells in these layers also showed depletion of dendritic spines. Neurons in the inner layers were preserved. Loss of receptive surfaces in neurons of the upper cortical layers in the frontal cortex are indicative of neuronal disconnection, and are "hidden" contributory morphological substrates for the development of dementia. Images PMID:1744652

  11. 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,…

  12. 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,…

  13. Mapping Task Switching in Frontal Cortex Through Neuropsychological Group Studies

    PubMed Central

    Shallice, Tim; Stuss, Donald T.; Picton, Terence W.; Alexander, Michael P.; Gillingham, Susan

    2008-01-01

    This paper considers evidence provided by large neuropsychological group studies and meta-analyses of functional imaging experiments on the location in frontal cortex of the subprocesses involved in the carrying out of task-switching paradigms. The function of the individual subprocesses is also considered in the light of analyses of the performance of normal subjects. PMID:18982110

  14. 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…

  15. 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…

  16. Projection from the perirhinal cortex to the frontal motor cortex in the rat.

    PubMed

    Kyuhou, Shin ichi; Gemba, Hisae

    2002-03-01

    Stimulation of the anterior perirhinal cortex (PERa) induced marked surface-negative and depth-positive field potentials in the rat frontal motor cortex (MC) including the rostral and caudal forelimb areas. Injection of biotinylated dextran into the PERa densely labeled axon terminals in the superficial layers of the MC, where vigorous unit responses were evoked after PERa stimulation, indicated that the perirhinal-frontal projection preferentially activates the superficial layer neurons of the MC.

  17. 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

  18. 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

  19. Utilization behavior after lesions restricted to the frontal cortex.

    PubMed

    Chapados, Catherine; Petrides, Michael

    2014-07-01

    Utilization behavior, which refers to the tendency of patients to use objects presented to them out of context and in the absence of instructions to use them, has been ascribed to dysfunction of the frontal cortex. However, careful examination of the reports of patients presenting utilization behavior shows that these patients had sustained widespread cerebral lesions extending beyond the frontal cortex and often involving massive subcortical damage. The present study examined whether utilization behavior can be observed in patients with lesions restricted to the prefrontal cortex and no more than the immediately subjacent white matter. All patients had surgical excisions, except for three patients in the frontal group who had sustained a cerebrovascular accident. A group of patients with excisions in the temporal lobe and a group of healthy participants were also studied for comparison. The investigation of utilization behavior took place in the context of a broader neuropsychological examination. There was no difference in the presence of utilization behavior in patients with lesions restricted to the prefrontal cortex in comparison with patients with temporal lobe lesions and carefully matched neurologically intact individuals. The results suggest that, in previous studies, the exhibition of utilization behavior by patients with extensive damage to the anterior part of the brain may have been due to damage to subcortical structures or to the prefrontal cortex in conjunction with subcortical damage.

  20. Frontal Cortex Neuropathology in Dementia Pugilistica

    PubMed Central

    Saing, Tommy; Dick, Malcolm; Nelson, Peter T.; Kim, Ronald C.; Cribbs, David H.

    2012-01-01

    Abstract Dementia pugilistica (DP) is associated with chronic traumatic brain injury (CTBI), and leads to a “punch drunk” syndrome characterized by impairments in memory and executive function, behavioral changes, and motor signs. Microscopic features include the accumulation of neurofibrillary tangles (NFTs), beta-amyloid (Aβ), and TAR DNA binding protein 43 (TDP-43) pathology. Here we describe detailed clinical and neuropathological data about a 55-year-old retired boxer (ApoE3/4), who presented with executive dysfunction and behavioral impairments. At autopsy, significant Aβ pathology was seen, primarily in the form of diffuse plaques. Tau pathology was extensive and was determined to be of Braak and Braak stage VI. Frontal white matter showed evidence of glial tau inclusions (astrocytes and oligodendroglia). Cerebrovascular pathology was minimal with patchy amyloid angiopathy. Inflammation was another key feature, including microglial activation and significant C1q labeling of neurons, along with NFTs. TDP-43-positive pathology was also observed. Inflammation may be a key inciting as well as propagating feature of DP neuropathology. PMID:22017610

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

    PubMed Central

    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 visuo-spatial 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 fronto-parietal 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 (FEF, PreCC/IFS) and parietal cortex (IPS1-IPS5, SPL1) and 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 superior parietal lobule (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

  2. Downregulation of the posterior medial frontal cortex prevents social conformity.

    PubMed

    Klucharev, Vasily; Munneke, Moniek A M; Smidts, Ale; Fernández, Guillén

    2011-08-17

    We often change our behavior to conform to real or imagined group pressure. Social influence on our behavior has been extensively studied in social psychology, but its neural mechanisms have remained largely unknown. Here we demonstrate that the transient downregulation of the posterior medial frontal cortex by theta-burst transcranial magnetic stimulation reduces conformity, as indicated by reduced conformal adjustments in line with group opinion. Both the extent and probability of conformal behavioral adjustments decreased significantly relative to a sham and a control stimulation over another brain area. The posterior part of the medial frontal cortex has previously been implicated in behavioral and attitudinal adjustments. Here, we provide the first interventional evidence of its critical role in social influence on human behavior.

  3. 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

  4. Neuronal correlates of metacognition in primate frontal cortex

    PubMed Central

    Middlebrooks, Paul G.; Sommer, Marc A.

    2012-01-01

    SUMMARY Humans are metacognitive: they monitor and control their cognition. Our hypothesis was that neuronal correlates of metacognition reside in the same brain areas responsible for cognition, including frontal cortex. Recent work demonstrated that non-human primates are capable of metacognition, so we recorded from single neurons in the frontal eye field, dorsolateral prefrontal cortex, and supplementary eye field of monkeys (Macaca mulatta) that performed a metacognitive visual-oculomotor task. The animals made a decision and reported it with a saccade, but received no immediate reward or feedback. Instead, they had to monitor their decision and bet whether it was correct. Activity was correlated with decisions and bets in all three brain areas, but putative metacognitive activity that linked decisions to appropriate bets occurred exclusively in the SEF. Our results offer a survey of neuronal correlates of metacognition and implicate the SEF in linking cognitive functions over short periods of time. PMID:22884334

  5. Recovery of frontal cortex-mediated visual behaviors following neurotrophic rescue of axotomized neurons in medial frontal cortex.

    PubMed

    Haun, F; Cunningham, T J

    1993-02-01

    Unilateral lesions extending across the boundary region of visual and parietal cortex in adult rats result in the death of 20-35% of neurons in layers II-III of the caudal third of medial frontal cortex ipsilaterally, a neuron population labeled with 3H-thymidine on the 19th day of gestation (E19). Additionally, there is a consistent 15% loss of these labeled neurons in an area between 50% and 60% of the distance along the caudal-rostral extent of medial frontal cortex, an area that may function analogously to the frontal eye field of primates. All of these neurons are rescued from axotomy-induced death by delivering into the posterior cortex lesion cavity for 2 weeks a macromolecular fraction of culture medium conditioned by embryonic primordia of the frontal-occipital pathway (CM). Moreover, the rescue is apparently permanent, with normal numbers of these neurons present in CM animals 6-7 weeks after the neurotrophic factor is no longer being supplied exogenously. Behaviorally, control operates receiving a similarly prepared fraction of unconditioned medium are significantly impaired in the number of trials needed to learn two visual discrimination tasks. This deficit is attributable in part to a bias in erroneous responses to the side contralateral to the lesion. The error bias reflects a failure to inhibit repeated incorrect responding contralaterally. In contrast, the CM animals learn both visual tasks in a normal number of trials and have no contralateral error bias. Rather, all CM animals have an contralateral error bias. Rather, all CM animals have an ipsilateral error bias (interpreted as an unmasking of the contralateral neglect expected after a parietal cortex lesion).(ABSTRACT TRUNCATED AT 250 WORDS)

  6. An inhibitory pull-push circuit in frontal cortex.

    PubMed

    Garcia-Junco-Clemente, Pablo; Ikrar, Taruna; Tring, Elaine; Xu, Xiangmin; Ringach, Dario L; Trachtenberg, Joshua T

    2017-03-01

    Push-pull is a canonical computation of excitatory cortical circuits. By contrast, we identify a pull-push inhibitory circuit in frontal cortex that originates in vasoactive intestinal polypeptide (VIP)-expressing interneurons. During arousal, VIP cells rapidly and directly inhibit pyramidal neurons; VIP cells also indirectly excite these pyramidal neurons via parallel disinhibition. Thus, arousal exerts a feedback pull-push influence on excitatory neurons-an inversion of the canonical push-pull of feedforward input.

  7. 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

  8. 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

  9. Ventrolateral and dorsomedial frontal cortex lesions impair mnemonic context retrieval.

    PubMed

    Chapados, Catherine; Petrides, Michael

    2015-02-22

    The prefrontal cortex appears to contribute to the mnemonic retrieval of the context within which stimuli are experienced, but only under certain conditions that remain to be clarified. Patients with lesions to the frontal cortex, the temporal lobe and neurologically intact individuals were tested for context memory retrieval when verbal stimuli (words) had been experienced across multiple (unstable context condition) or unique (stable context condition) contexts; basic recognition memory of these words-in-contexts was also tested. Patients with lesions to the right ventrolateral prefrontal cortex (VLPFC) were impaired on context retrieval only when the words had been seen in multiple contexts, demonstrating that this prefrontal region is critical for active retrieval processing necessary to disambiguate memory items embedded across multiple contexts. Patients with lesions to the left dorsomedial prefrontal region were impaired on both context retrieval conditions, regardless of the stability of the stimulus-to-context associations. Conversely, prefrontal lesions sparing the ventrolateral and dorsomedial regions did not impair context retrieval. Only patients with temporal lobe excisions were impaired on basic recognition memory. The results demonstrate a basic contribution of the left dorsomedial frontal region to mnemonic context retrieval, with the VLPFC engaged, selectively, when contextual relations are unstable and require disambiguation.

  10. The cerebral cortex in fetal Down syndrome.

    PubMed

    Unterberger, U; Lubec, G; Dierssen, M; Stoltenburg-Didinger, G; Farreras, J C; Budka, H

    2003-01-01

    Brain histopathology of 32 fetuses with Down syndrome was compared to that of 25 age-matched normal controls and 9 brains of fetuses of HIV positive mothers. Four cases of Down syndrome and 1 HIV case showed microdysgenesia of the cerebral cortex. As the pathogenetic background of cortical irregularities is presently not known, we analyzed the neuronal expression of drebrin, an actin-binding protein of neuronal dendritic spines. This protein is thought to play a role in synaptic formation and was recently shown to be manifold reduced in brains of fetuses with Down syndrome. However, immunocytochemistry revealed no differences in drebrin expression pattern between Down patients and controls. We conclude that cerebral cortical microdysgenesia is an infrequent non-specific pathology in fetal Down syndrome.

  11. 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.

  12. Retained fetal adrenal cortex in a cynomolgus macaque (Macaca fascicularis).

    PubMed

    Radi, Zaher; Evans, Mark

    2014-10-01

    An incidental, bilateral, retained fetal adrenal cortex was detected in a male cynomolgus macaque (age, approximately 2.4 y) used in a 4-week toxicology study. Microscopic examination of the adrenal gland cortex zone revealed the presence of additional solid sheets and columns of cells supported by vascular capillary bed and composed of large polyhedral cells with abundant eosinophilic, slightly finely vacuolated cytoplasm that surrounded the entire circumference of the medulla. Nuclei were vesicular, round to oval with prominent small nucleoli. There was no evidence for inflammation or cellular degeneration. Based on the microscopic examination, a diagnosis of retained fetal cortex of the adrenal gland was made. This morphologic change resembles fetal cortex in human infants. To our knowledge, this case description is the first report of a cynomolgus macaque with the rare entity of retained fetal cortex, which should not be misinterpreted as a test article-related change. Copyright © 2014 Elsevier GmbH. All rights reserved.

  13. Corticofugal GABAergic projection neurons in the mouse frontal cortex

    PubMed Central

    Tomioka, Ryohei; Sakimura, Kenji; Yanagawa, Yuchio

    2015-01-01

    Cortical projection neurons are classified by hodology in corticocortical, commissural and corticofugal subtypes. Although cortical projection neurons had been regarded as only glutamatergic neurons, recently corticocortical GABAergic projection neurons has been also reported in several species. Here, we demonstrate corticofugal GABAergic projection neurons in the mouse frontal cortex. We employed viral-vector-mediated anterograde tracing, classical retrograde tracing, and immunohistochemistry to characterize neocortical GABAergic projection neurons. Injections of the Cre-dependent adeno-associated virus into glutamate decarboxylase 67 (GAD67)-Cre knock-in mice revealed neocortical GABAergic projections widely to the forebrain, including the cerebral cortices, caudate putamen (CPu), ventral pallidum (VP), lateral globus pallidus (LGP), nucleus accumbens, and olfactory tubercle (Tu). Minor GABAergic projections were also found in the mediodorsal thalamic nucleus, diagonal band of Broca, medial globus pallidus, substantial nigra, and dorsal raphe nucleus. Retrograde tracing studies also demonstrated corticofugal GABAergic projection neurons in the mouse frontal cortex. Further immunohistochemical screening with neurochemical markers revealed the majority of corticostriatal GABAergic projection neurons were positive for somatostatin (SS)-immunoreactivity. In contrast, corticothalamic GABAergic projection neurons were not identified by representative neurochemical markers for GABAergic neurons. These findings suggest that corticofugal GABAergic projection neurons are heterogeneous in terms of their neurochemical properties and target nuclei, and provide axonal innervations mainly to the nuclei in the basal ganglia. PMID:26578895

  14. The Interplay between Estrogen and Fetal Adrenal Cortex

    PubMed Central

    Kaludjerovic, Jovana; Ward, Wendy E.

    2012-01-01

    Estrogen is a steroid hormone that regulates embryogenesis, cell proliferation and differentiation, organogenesis, the timing of parturition, and fetal imprinting by carrying chemical messages from glands to cells within tissues or organs in the body. During development, placenta is the primary source of estrogen production but estrogen can only be produced if the fetus or the mother supplies dehydroepiandrosterone (DHEA), the estrogen prohormone. Studies show that the fetal zone of the fetal adrenal cortex supplies 60% of DHEA for placental estrogen production, and that placental estrogen in turn modulates the morphological and functional development of the fetal adrenal cortex. As such, in developed countries where humans are exposed daily to environmental estrogens, there is concern that the development of fetal adrenal cortex, and in turn, placental estrogen production may be disrupted. This paper discusses fetal adrenal gland development, how endogenous estrogen regulates the structure and function of the fetal adrenal cortex, and highlights the potential role that early life exposure to environmental estrogens may have on the development and endocrinology of the fetal adrenal cortex. PMID:22536492

  15. [Effect of Heroin on DLG4 Expression in Hippocampus, Amygdala and Frontal Cortex of Rats].

    PubMed

    Luo, Liang-ming; Gong, Qun; Liu, Jian-feng; Zhao, Ming-quan; Chen, Dong-dong; Xie, Yao-yao; Zhu, Hua

    2015-06-01

    To observe the expression of discs large homolog 4 (DLG4) protein in hippocampus, amygdala and frontal cortex of rats and evaluate postsynaptic density in heroin dependence. The rat heroin dependent model was established by increasing intraperitoneal injection of heroin. DLG4 proteins in hippocampus, amygdala and frontal cortex of heroin dependent 9, 18, 36 days rats were detected with immunohistochemical staining and compared with that in the control group. DLG4 proteins in hippocampus, amygdala and frontal cortex were gradually reduced with extension of heroin dependent time. Heroin dependence can affect postsynaptic density of hippocampus, amygdala and frontal cortex. The changes become more apparent with extension of heroin dependence time.

  16. Oxidative and glicolytic metabolism of the frontal cortex (latero-frontal) and of the posterior cortex (latero-occipital) in relation with the sexual activity of the rat.

    PubMed

    Menéndez-Patterson, A; Florez-Lozano, J A; Marin, B

    1976-01-01

    The authors of this paper have ascertained the glycolytic metabolism and the oxidative metabolism (intake of QO2), of the frontal and posterior cortex in female rats at different stages of the sexual cycle, as also in ovariectomized animals, by the intake of glucose and the production of lactates. The results indicate a statistically significant increase of the oxidative metabolism of the posterior cortex (latero-occipital) in the estrual and proestrual phases, in comparisons with the diestral phase. The frontal cortex (latero-frontal) did not show any significant difference; moreover, the glycolitic metabolism did not alter in any of the tissues under observation. These findings, seem to suggest possible participation of the posterior cortex (latero-occipital) on the regulation of sexual cycle of the rat. The activation of this cortex occurs through the preponderant imbricantion of the tri-carboxylic acid cycle.

  17. Developmental and functional biology of the primate fetal adrenal cortex.

    PubMed

    Mesiano, S; Jaffe, R B

    1997-06-01

    The unique characteristics of the primate (particularly human) fetal adrenal were first realized in the early 1900s when its morphology was examined in detail and compared with that of other species. The unusual architecture of the human fetal adrenal cortex, with its unique and disproportionately enlarged fetal zone, its compact definitive zone, and its dramatic remodeling soon after birth captured the interest of developmental anatomists. Many detailed anatomical studies describing the morphology of the developing human fetal adrenal were reported between 1920 and 1960, and these morphological descriptions have not changed significantly. More recently, it has become clear that fetal adrenal cortical growth involves cellular hypertrophy, hyperplasia, apoptosis, and migration and is best described by the migration theory, i.e. cells proliferate in the periphery, migrate centripetally, differentiate during their migration to form the functional cortical zones, and then likely undergo apoptosis in the center of the cortex. Consistent with this model, cells of intermediate phenotype, arranged in columnar cords typical of migration, have been identified between the definitive and fetal zones. This cortical area has been referred to as the transitional zone and, based on the expression of steroidogenic enzymes, we consider it to be a functionally distinct cortical zone. Elegant experiments during the 1950s and 1960s demonstrated the central role of the primate fetal adrenal cortex in establishing the estrogenic milieu of pregnancy. Those findings were among the first indications of the function and physiological role of the human fetal adrenal cortex and led Diczfalusy and co-workers to propose the concept of the feto-placental unit, in which DHEA-S produced by the fetal adrenal cortex is used by the placenta for estrogen synthesis. Tissue and cell culture techniques, together with improved steroid assays, revealed that the fetal zone is the primary source of DHEA

  18. The Roles of Orbital Frontal Cortex in the Modulation of Antisocial Behavior

    ERIC Educational Resources Information Center

    Blair, R. J. R.

    2004-01-01

    This article considers potential roles of orbital frontal cortex in the modulation of antisocial behavior. Two forms of aggression are distinguished: reactive aggression elicited in response to frustration/threat and goal directed, instrumental aggression. It is suggested that orbital frontal cortex is directly involved in the modulation of…

  19. Prenatal Alcohol Exposure Modifies Glucocorticoid Receptor Subcellular Distribution in the Medial Prefrontal Cortex and Impairs Frontal Cortex-Dependent Learning

    PubMed Central

    Allan, Andrea M.; Goggin, Samantha L.; Caldwell, Kevin K.

    2014-01-01

    Prenatal alcohol exposure (PAE) has been shown to impair learning, memory and executive functioning in children. Perseveration, or the failure to respond adaptively to changing contingencies, is a hallmark on neurobehavioral assessment tasks for human fetal alcohol spectrum disorder (FASD). Adaptive responding is predominantly a product of the medial prefrontal cortex (mPFC) and is regulated by corticosteroids. In our mouse model of PAE we recently reported deficits in hippocampal formation-dependent learning and memory and a dysregulation of hippocampal formation glucocorticoid receptor (GR) subcellular distribution. Here, we examined the effect of PAE on frontal cortical-dependent behavior, as well as mPFC GR subcellular distribution and the levels of regulators of intracellular GR transport. PAE mice displayed significantly reduced response flexibility in a Y-maze reversal learning task. While the levels of total nuclear GR were reduced in PAE mPFC, levels of GR phosphorylated at serines 203, 211 and 226 were not significantly changed. Cytosolic, but not nuclear, MR levels were elevated in the PAE mPFC. The levels of critical GR trafficking proteins, FKBP51, Hsp90, cyclophilin 40, dynamitin and dynein intermediate chain, were altered in PAE mice, in favor of the exclusion of GR from the nucleus, indicating dysregulation of GR trafficking. Our findings suggest that there may be a link between a deficit in GR nuclear localization and frontal cortical learning deficits in prenatal alcohol-exposed mice. PMID:24755652

  20. The Role of Medial Frontal Cortex in Action Anticipation in Professional Badminton Players.

    PubMed

    Xu, Huan; Wang, Pin; Ye, Zhuo'er; Di, Xin; Xu, Guiping; Mo, Lei; Lin, Huiyan; Rao, Hengyi; Jin, Hua

    2016-01-01

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

  1. The Role of Medial Frontal Cortex in Action Anticipation in Professional Badminton Players

    PubMed Central

    Xu, Huan; Wang, Pin; Ye, Zhuo’er; Di, Xin; Xu, Guiping; Mo, Lei; Lin, Huiyan; Rao, Hengyi; Jin, Hua

    2016-01-01

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

  2. Reversed Procrastination by Focal Disruption of Medial Frontal Cortex.

    PubMed

    Jha, Ashwani; Diehl, Beate; Scott, Catherine; McEvoy, Andrew W; Nachev, Parashkev

    2016-11-07

    An enduring puzzle in the neuroscience of voluntary action is the origin of the remarkably wide dispersion of the reaction time distribution, an interval far greater than is explained by synaptic or signal transductive noise [1, 2]. That we are able to change our planned actions-a key criterion of volition [3]-so close to the time of their onset implies decision-making must reach deep into the execution of action itself [4-6]. It has been influentially suggested the reaction time distribution therefore reflects deliberate neural procrastination [7], giving alternative response tendencies sufficient time for fair competition in pursuing a decision threshold that determines which one is behaviorally manifest: a race model, where action selection and execution are closely interrelated [8-11]. Although the medial frontal cortex exhibits a sensitivity to reaction time on functional imaging that is consistent with such a mechanism [12-14], direct evidence from disruptive studies has hitherto been lacking. If movement-generating and movement-delaying neural substrates are closely co-localized here, a large-scale lesion will inevitably mask any acceleration, for the movement itself could be disrupted. Circumventing this problem, here we observed focal intracranial electrical disruption of the medial frontal wall in the context of the pre-surgical evaluation of two patients with epilepsy temporarily reversing such hypothesized procrastination. Effector-specific behavioral acceleration, time-locked to the period of electrical disruption, occurred exclusively at a specific locus at the ventral border of the pre-supplementary motor area. A cardinal prediction of race models of voluntary action is thereby substantiated in the human brain. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Processing of emotional vocalizations in bilateral inferior frontal cortex.

    PubMed

    Frühholz, Sascha; Grandjean, Didier

    2013-12-01

    A current view proposes that the right inferior frontal cortex (IFC) is particularly responsible for attentive decoding and cognitive evaluation of emotional cues in human vocalizations. Although some studies seem to support this view, an exhaustive review of all recent imaging studies points to an important functional role of both the right and the left IFC in processing vocal emotions. Second, besides a supposed predominant role of the IFC for an attentive processing and evaluation of emotional voices in IFC, these recent studies also point to a possible role of the IFC in preattentive and implicit processing of vocal emotions. The studies specifically provide evidence that both the right and the left IFC show a similar anterior-to-posterior gradient of functional activity in response to emotional vocalizations. This bilateral IFC gradient depends both on the nature or medium of emotional vocalizations (emotional prosody versus nonverbal expressions) and on the level of attentive processing (explicit versus implicit processing), closely resembling the distribution of terminal regions of distinct auditory pathways, which provide either global or dynamic acoustic information. Here we suggest a functional distribution in which several IFC subregions process different acoustic information conveyed by emotional vocalizations. Although the rostro-ventral IFC might categorize emotional vocalizations, the caudo-dorsal IFC might be specifically sensitive to their temporal features. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Frontal cerebral cortex blood flow, oxygen delivery and oxygenation during normoxic and hypoxic exercise in athletes

    PubMed Central

    Vogiatzis, Ioannis; Louvaris, Zafeiris; Habazettl, Helmut; Athanasopoulos, Dimitris; Andrianopoulos, Vasilis; Cherouveim, Evgenia; Wagner, Harrieth; Roussos, Charis; Wagner, Peter D; Zakynthinos, Spyros

    2011-01-01

    Abstract During maximal hypoxic exercise, a reduction in cerebral oxygen delivery may constitute a signal to the central nervous system to terminate exercise. We investigated whether the rate of increase in frontal cerebral cortex oxygen delivery is limited in hypoxic compared to normoxic exercise. We assessed frontal cerebral cortex blood flow using near-infrared spectroscopy and the light-absorbing tracer indocyanine green dye, as well as frontal cortex oxygen saturation ( %) in 11 trained cyclists during graded incremental exercise to the limit of tolerance (maximal work rate, WRmax) in normoxia and acute hypoxia (inspired O2 fraction (), 0.12). In normoxia, frontal cortex blood flow and oxygen delivery increased (P < 0.05) from baseline to sub-maximal exercise, reaching peak values at near-maximal exercise (80% WRmax: 287 ± 9 W; 81 ± 23% and 75 ± 22% increase relative to baseline, respectively), both leveling off thereafter up to WRmax (382 ± 10 W). Frontal cortex % did not change from baseline (66 ± 3%) throughout graded exercise. During hypoxic exercise, frontal cortex blood flow increased (P = 0.016) from baseline to sub-maximal exercise, peaking at 80% WRmax (213 ± 6 W; 60 ± 15% relative increase) before declining towards baseline at WRmax (289 ± 5 W). Despite this, frontal cortex oxygen delivery remained unchanged from baseline throughout graded exercise, being at WRmax lower than at comparable loads (287 ± 9 W) in normoxia (by 58 ± 12%; P = 0.01). Frontal cortex % fell from baseline (58 ± 2%) on light and moderate exercise in parallel with arterial oxygen saturation, but then remained unchanged to exhaustion (47 ± 1%). Thus, during maximal, but not light to moderate, exercise frontal cortex oxygen delivery is limited in hypoxia compared to normoxia. This limitation could potentially constitute the signal to limit maximal exercise capacity in hypoxia. PMID:21727220

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

    PubMed Central

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

    2015-01-01

    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

  6. 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…

  7. 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…

  8. 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

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

    PubMed

    Robinson, Gail; Shallice, Tim; Bozzali, Marco; Cipolotti, Lisa

    2012-07-01

    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.

  10. Longitudinal evidence for diminished frontal cortex function in aging

    PubMed Central

    Nyberg, Lars; Salami, Alireza; Andersson, Mikael; Eriksson, Johan; Kalpouzos, Grégoria; Kauppi, Karolina; Lind, Johanna; Pudas, Sara; Persson, Jonas; Nilsson, Lars-Göran

    2010-01-01

    Cross-sectional estimates of age-related changes in brain structure and function were compared with 6-y longitudinal estimates. The results indicated increased sensitivity of the longitudinal approach as well as qualitative differences. Critically, the cross-sectional analyses were suggestive of age-related frontal overrecruitment, whereas the longitudinal analyses revealed frontal underrecruitment with advancing age. The cross-sectional observation of overrecruitment reflected a select elderly sample. However, when followed over time, this sample showed reduced frontal recruitment. These findings dispute inferences of true age changes on the basis of age differences, hence challenging some contemporary models of neurocognitive aging, and demonstrate age-related decline in frontal brain volume as well as functional response. PMID:21156826

  11. 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.

  12. Alterations of interneurons in the striatum and frontal cortex of mice during postnatal development.

    PubMed

    Eto, Risa; Abe, Manami; Kimoto, Hiroki; Imaoka, Eri; Kato, Hiroyuki; Kasahara, Jiro; Araki, Tsutomu

    2010-08-01

    We investigated the postnatal alterations of neuronal nuclei (NeuN)-positive neurons, parvalbumin (PV)-positive interneurons, neuronal nitric oxide synthase (nNOS)-positive interneurons, and neurotrophic factors in the mouse striatum and frontal cortex using immunohistochemistry. NeuN, PV, nNOS, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) immunoreactivity were measured in 1-, 2-, 4- and 8-week-old mice. Total number of NeuN-positive neurons was unchanged in the mouse striatum and frontal cortex from 1 up to 8 weeks of age. In contrast, a significant decrease in the number of PV-positive interneurons was observed in the striatum and frontal cortex of 1-, 2- and 4-week-old mice. Furthermore, a significant increase of nNOS-positive interneurons was found in the striatum and frontal cortex of 1- and/or 2-week-old mice. NGF-positive neurons were unchanged in the mouse striatum from 1 up to 8 weeks of age. In the frontal cortex, a significant increase in the number of NGF-positive neurons was observed only in 1-week-old mice. In contrast, a significant increase in the number of NGF-positive glia 1 cells was found in the striatum and frontal cortex of 4-week-old mice. Our double-labeled immunostaining showed that nNOS immunoreactivity was not found in PV-immunopositive interneurons. Furthermore, BDNF immunoreactivity was observed in both nNOS-positive and PV-positive interneurons in the striatum of 1- or 2-week-old mice. These results show that the maturation of nNOS-immunopositive interneurons precedes the maturation of PV-immunopositive interneurons in the striatum and frontal cortex during postnatal development. Furthermore, our results demonstrate that the expression of BDNF may play some role in the maturation of interneurons in the striatum and frontal cortex during postnatal development. Moreover, our findings suggest that the expression of NGF in glia cells may play some role in the maturation of glial cells and PV-positive interneurons

  13. MRI volume of the medial frontal cortex predicts financial capacity in patients with mild Alzheimer's disease.

    PubMed

    Stoeckel, Luke E; Stewart, Christopher C; Griffith, H Randall; Triebel, Kristen; Okonkwo, Ozioma C; den Hollander, Jan A; Martin, Roy C; Belue, Katherine; Copeland, Jacquelynn N; Harrell, Lindy E; Brockington, John C; Clark, David G; Marson, Daniel C

    2013-09-01

    Persons with mild Alzheimer's disease (AD) have significant deficits in financial abilities. This study examined the relationship between brain structure volumes, cognition, and financial capacity in patients with mild AD. Sixteen mild AD patients and 16 older adult comparisons completed the Financial Capacity Instrument (FCI), a psychometric measure of financial abilities, and also underwent magnetic resonance imaging (MRI) to obtain volumes of the bilateral hippocampi, angular gyri, precunei, and medial and dorsolateral frontal cortices. Mild AD patients performed significantly below comparisons on the FCI and had significantly smaller hippocampi. Among mild AD patients, FCI performance was moderately correlated with frontal (medial and dorsolateral frontal cortex) and posterior (angular gyri and precunei) cortical volumes. Stepwise regression demonstrated that medial frontal cortex volume predicted FCI score. The relationship between medial frontal cortex volume and overall FCI score was partially mediated by two measures of simple attention (DRS Attention, DRS Construction). The findings suggest that medial frontal cortex atrophy and associated declines in simple attention play an increasingly important role in declining financial skills in patients with mild AD.

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

    PubMed

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

    2008-01-31

    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.

  15. Vulnerability of the medial frontal corticospinal projection accompanies combined lateral frontal and parietal cortex injury in rhesus monkey.

    PubMed

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

    2015-03-01

    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 spontaneous 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 with 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 CSP. 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. [2010] J. Comp. Neurol. 518:586-621), 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.

  16. Fluid intelligence loss linked to restricted regions of damage within frontal and parietal cortex

    PubMed Central

    Woolgar, Alexandra; Parr, Alice; Cusack, Rhodri; Thompson, Russell; Nimmo-Smith, Ian; Torralva, Teresa; Roca, Maria; Antoun, Nagui; Manes, Facundo; Duncan, John

    2010-01-01

    Tests of fluid intelligence predict success in a wide range of cognitive activities. Much uncertainty has surrounded brain lesions producing deficits in these tests, with standard group comparisons delivering no clear result. Based on findings from functional imaging, we propose that the uncertainty of lesion data may arise from the specificity and complexity of the relevant neural circuit. Fluid intelligence tests give a characteristic pattern of activity in posterolateral frontal, dorsomedial frontal, and midparietal cortex. To test the causal role of these regions, we examined fluid intelligence in 80 patients with focal cortical lesions. Damage to each of the proposed regions predicted fluid intelligence loss, whereas damage outside these regions was not predictive. The results suggest that coarse group comparisons (e.g., frontal vs. posterior) cannot show the neural underpinnings of fluid intelligence tests. Instead, deficits reflect the extent of damage to a restricted but complex brain circuit comprising specific regions within both frontal and posterior cortex. PMID:20679241

  17. Fluid intelligence loss linked to restricted regions of damage within frontal and parietal cortex.

    PubMed

    Woolgar, Alexandra; Parr, Alice; Cusack, Rhodri; Thompson, Russell; Nimmo-Smith, Ian; Torralva, Teresa; Roca, Maria; Antoun, Nagui; Manes, Facundo; Duncan, John

    2010-08-17

    Tests of fluid intelligence predict success in a wide range of cognitive activities. Much uncertainty has surrounded brain lesions producing deficits in these tests, with standard group comparisons delivering no clear result. Based on findings from functional imaging, we propose that the uncertainty of lesion data may arise from the specificity and complexity of the relevant neural circuit. Fluid intelligence tests give a characteristic pattern of activity in posterolateral frontal, dorsomedial frontal, and midparietal cortex. To test the causal role of these regions, we examined fluid intelligence in 80 patients with focal cortical lesions. Damage to each of the proposed regions predicted fluid intelligence loss, whereas damage outside these regions was not predictive. The results suggest that coarse group comparisons (e.g., frontal vs. posterior) cannot show the neural underpinnings of fluid intelligence tests. Instead, deficits reflect the extent of damage to a restricted but complex brain circuit comprising specific regions within both frontal and posterior cortex.

  18. Alterations in cortical thickness and neuronal density in the frontal cortex of Albert Einstein.

    PubMed

    Anderson, B; Harvey, T

    1996-06-07

    Neuronal density, neuron size, and the number of neurons under 1 mm2 of cerebral cortical surface area were measured in the right pre-frontal cortex of Albert Einstein and five elderly control subjects. Measurement of neuronal density used the optical dissector technique on celloidin-embedded cresyl violet-stained sections. The neurons counted provided a systematic random sample for the measurement of cell body cross-sectional area. Einstein's cortex did not differ from the control subjects in the number of neurons under 1 mm2 of cerebral cortex or in mean neuronal size. Because Einstein's cortex was thinner than the controls he had a greater neuronal density.

  19. Induction of neuroserpin expression in rat frontal cortex after chronic antidepressant treatment and electroconvulsive treatment.

    PubMed

    Tanaka, Satoshi; Yamada, Misa; Kitahara, Sari; Higuchi, Teruhiko; Honda, Kazuo; Kamijima, Kunitoshi; Yamada, Mitsuhiko

    2006-02-01

    Using expressed sequence tag (EST) analysis, we previously identified certain molecular machinery that mediates antidepressant effects. To date, several partial cDNA fragments, termed antidepressant-related genes (ADRGs), have been isolated as ESTs from rat brain. In the present study, we identified two of the ADRGs to be rat neuroserpin. Using real-time quantitative PCR, we demonstrated increased neuroserpin mRNA expression in rat frontal cortex after chronic treatment with several classes of antidepressants, including imipramine, fluoxetine, sertraline, and venlafaxine. Electroconvulsive treatment (ECT), another therapeutic treatment for depression, also increased neuroserpin expression in rat frontal cortex. Neuroserpin is a serine protease inhibitor that is implicated in the regulation of synaptic plasticity, neuronal migration, and axogenesis in the central nervous system. In conclusion, our results support the hypothesis that neuroserpin-mediated plastic changes in frontal cortex may underlie the therapeutic action of antidepressants and ECT.

  20. Abstract rule learning: the differential effects of lesions in frontal cortex.

    PubMed

    Kayser, Andrew S; D'Esposito, Mark

    2013-01-01

    Learning progressively more abstract stimulus-response mappings requires progressively more anterior regions of the lateral frontal cortex. Using an individual differences approach, we studied subjects with frontal lesions performing a hierarchical reinforcement-learning task to investigate how frontal cortex contributes to abstract rule learning. We predicted that subjects with lesions of the left pre-premotor (pre-PMd) cortex, a region implicated in abstract rule learning, would demonstrate impaired acquisition of second-order, as opposed to first-order, rules. We found that 4 subjects with such lesions did indeed demonstrate a second-order rule-learning impairment, but that these subjects nonetheless performed better than subjects with other frontal lesions in a second-order rule condition. This finding resulted from both their restricted exploration of the feature space and the task structure of this condition, for which they identified partially representative first-order rules. Significantly, across all subjects, suboptimal but above-chance performance in this condition correlated with increasing disconnection of left pre-PMd from the putative functional hierarchy, defined by reduced functional connectivity between left pre-PMd and adjacent nodes. These findings support the theory that activity within lateral frontal cortex shapes the search for relevant stimulus-response mappings, while emphasizing that the behavioral correlate of impairments depends critically on task structure.

  1. Autobiographical memory of the recent past following frontal cortex or temporal lobe excisions.

    PubMed

    Thaiss, Laila; Petrides, Michael

    2008-08-01

    Previous research has raised questions regarding the necessity of the frontal cortex in autobiographical memory and the role that it plays in actively retrieving contextual information associated with personally relevant events. Autobiographical memory was studied in patients with unilateral excisions restricted to the frontal cortex or temporal lobe involving the amygdalo-hippocampal region and in normal controls using an event-sampling method. We examined accuracy of free recall, use of strategies during retrieval and memory for specific aspects of the autobiographical events, including temporal order. Patients with temporal lobe excisions were impaired in autobiographical recall. By contrast, patients with frontal cortical excisions exhibited normal autobiographical recall but were less likely to use temporal order spontaneously to organize event retrieval. Instruction to organize retrieval by temporal order failed to improve recall in temporal lobe patients and increased the incidence of plausible intrusion errors in left temporal patients. In contrast, patients with frontal cortical excisions now surpassed control subjects in recall of autobiographical events. Furthermore, the retrieval accuracy for the temporal order of diary events was not impaired in these patients. In a subsequent cued recall test, temporal lobe patients were impaired in their memory for the details of the diary events and their context. In conclusion, a basic impairment in autobiographical memory (including memory for temporal context) results from damage to the temporal lobe and not the frontal cortex. Patients with frontal excisions fail to use organizational strategies spontaneously to aid retrieval but can use these effectively if instructed to do so.

  2. Reduced Frontal Cortex Efficiency is Associated with Lower White Matter Integrity in Aging

    PubMed Central

    Zhu, Zude; Johnson, Nathan F.; Kim, Chobok; Gold, Brian T.

    2015-01-01

    Increased frontal cortex activation during cognitive task performance is common in aging but remains poorly understood. Here we explored patterns of age-related frontal brain activations under multiple task performance conditions and their relationship to white matter (WM) microstructure. Groups of younger (N = 28) and older (N = 33) participants completed a task-switching paradigm while functional magnetic resonance imaging (fMRI) was performed, and rested while diffusion tensor imaging was performed. Results from fMRI analyses indicated age-related increases in frontal brain activations under conditions of poorer performance in the older group (the nonswitch and switch conditions) and for a contrast in which behavioral performance was equated (older group nonswitch condition vs. younger group switch condition). Within the older adult group, higher frontal activation was associated with poorer behavioral performance under all task conditions. In 2 regions in right frontal cortex, blood oxygen level–dependent (BOLD) magnitudes were negatively correlated with WM integrity in tracts connecting these structures with other task-relevant frontoparietal and striatal regions. Our results link age-related declines in the efficiency of frontal cortex functioning with lower WM integrity in aging. PMID:23960206

  3. Functional Activation of the Human Ventrolateral Frontal Cortex During Mnemonic Retrieval of Verbal Information

    NASA Astrophysics Data System (ADS)

    Petrides, Michael; Alivisatos, Bessie; Evans, Alan C.

    1995-06-01

    Regional cerebral blood flow was measured with positron emission tomography during the performance of a verbal free recall task, a verbal paired associate task, and tasks that required the production of verbal responses either by speaking or writing. Examination of the differences in regional cerebral blood flow between these conditions demonstrated that the left ventrolateral frontal cortical area 45 is involved in the recall of verbal information from long-term memory, in addition to its contribution to speech. The act of writing activated a network of areas involving posterior parietal cortex and sensorimotor areas but not ventrolateral frontal cortex.

  4. 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

  5. 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.

  6. Patches of face-selective cortex in the macaque frontal lobe.

    PubMed

    Tsao, Doris Y; Schweers, Nicole; Moeller, Sebastian; Freiwald, Winrich A

    2008-08-01

    In primates, specialized occipital-temporal face areas support the visual analysis of faces, but it is unclear whether similarly specialized areas exist in the frontal lobe. Using functional magnetic resonance imaging in alert macaques, we identified three discrete regions of highly face-selective cortex in ventral prefrontal cortex, one of which was strongly lateralized to the right hemisphere. These prefrontal face patches may constitute dedicated modules for retrieving and responding to facial information.

  7. The rat retrosplenial cortex as a link for frontal functions: A lesion analysis.

    PubMed

    Powell, Anna L; Nelson, Andrew J D; Hindley, Emma; Davies, Moira; Aggleton, John P; Vann, Seralynne D

    2017-09-29

    Cohorts of rats with excitotoxic retrosplenial cortex lesions were tested on four behavioural tasks sensitive to dysfunctions in prelimbic cortex, anterior cingulate cortex, or both. In this way the study tested whether retrosplenial cortex has nonspatial functions that reflect its anatomical interactions with these frontal cortical areas. In Experiment 1, retrosplenial cortex lesions had no apparent effect on a set-shifting digging task that taxed intradimensional and extradimensional attention, as well as reversal learning. Likewise, retrosplenial cortex lesions did not impair a strategy shift task in an automated chamber, which involved switching from visual-based to response-based discriminations and, again, included a reversal (Experiment 2). Indeed, there was evidence that the retrosplenial lesions aided the initial switch to response-based selection. No lesion deficit was found on an automated cost-benefit task that pitted size of reward against effort to achieve that reward (Experiment 3). Finally, while retrosplenial cortex lesions affected matching-to-place task in a T-maze, the profile of deficits differed from that associated with prelimbic cortex damage (Experiment 4). When the task was switched to a nonmatching design, retrosplenial cortex lesions had no apparent effect on performance. The results from the four experiments show that many frontal tasks do not require the retrosplenial cortex, highlighting the specificity of their functional interactions. The results show how retrosplenial cortex lesions spare those learning tasks in which there is no mismatch between the internal and external representations used to guide behavioural choice. In addition, these experiments further highlight the importance of the retrosplenial cortex in solving tasks with a spatial component. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

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

    PubMed Central

    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.

    2016-01-01

    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. 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…

  11. 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…

  12. 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…

  13. Orbital frontal cortex in treatment naïve pediatric obsessive-compulsive disorder

    PubMed Central

    MacMaster, Frank; Vora, Anvi; Easter, Phillip; Rix, Carrie; Rosenberg, David

    2010-01-01

    The orbital frontal cortex (OFC) has been implicated in obsessive-compulsive disorder (OCD). Twenty-eight treatment-naïve pediatric OCD patients and twenty-one controls were examined using magnetic resonance imaging. OCD patients had larger right but not left OFC white matter volume than controls. This is fresh evidence implicating white matter in OCD. PMID:20074911

  14. 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.

  15. 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…

  16. 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…

  17. Differential Effect of Postnatal Lead Exposure on Gene Expression in the Hippocampus and Frontal Cortex

    PubMed Central

    Schneider, J.S.; Mettil, W.; Anderson, D.W.

    2011-01-01

    Although developmental lead exposure is known to have detrimental effects on a variety of cognitive functions that depend on the integrity of the hippocampus and frontal cortex, little is known about how low levels of lead exposure affect expression of key families of genes in these structures. The present study examined the effects of exposure to environmentally-relevant levels of lead during the sensitive early post-weaning period in the rat on the expression profiles of a select number of neurobiologically relevant genes (i.e., genes for neurotrophic factors, NMDA receptors, metabotropic glutamate receptors, synaptic function/plasticity, cell signaling, and transcription/regulation) in the rat hippocampus and frontal cortex. Exposure to lead (180 and 375 ppm lead acetate in food for 30 days) significantly increased blood lead levels (5.8 to 10.3 μg/dl) and significantly affected expression of many of the genes examined. In many instances, lead exposure had different effects on the same gene depending on the brain region in which the expression of that gene was examined. Gene expression in the frontal cortex was often more sensitive to modification than gene expression in the hippocampus. These results suggest that even past infancy, exposures to low levels of lead can have significant effects on gene expression in frontal cortex and the hippocampus with the potential to exert long-term effects on behavior and cognition. PMID:22160880

  18. 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.

  19. 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.

  20. Transcranial magnetic stimulation reveals complex cognitive control representations in the rostral frontal cortex.

    PubMed

    Bahlmann, J; Beckmann, I; Kuhlemann, I; Schweikard, A; Münte, T F

    2015-08-06

    Convergent evidence suggests that the lateral frontal cortex is at the heart of a brain network subserving cognitive control. Recent theories assume a functional segregation along the rostro-caudal axis of the lateral frontal cortex based on differences in the degree of complexity of cognitive control. However, the functional contribution of specific rostral and caudal sub-regions remains elusive. Here we investigate the impact of disrupting rostral and caudal target regions on cognitive control processes, using Transcranial Magnetic Stimulation (TMS). Participants performed three different task-switching conditions that assessed differences in the degree of complexity of cognitive control processes, after temporally disrupting rostral, or caudal target regions, or a control region. Disrupting the rostral lateral frontal region specifically impaired behavioral performance of the most complex task-switching condition, in comparison to the caudal target region and the control region. These novel findings shed light on the neuroanatomical architecture supporting control over goal-directed behavior.

  1. 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.

  2. 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.

  3. 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

  4. A network centred on the inferior frontal cortex is critically involved in levodopa-induced dyskinesias.

    PubMed

    Cerasa, Antonio; Koch, Giacomo; Donzuso, Giulia; Mangone, Graziella; Morelli, Maurizio; Brusa, Livia; Stampanoni Bassi, Mario; Ponzo, Viviana; Picazio, Silvia; Passamonti, Luca; Salsone, Maria; Augimeri, Antonio; Caltagirone, Carlo; Quattrone, Aldo

    2015-02-01

    Levodopa-induced dyskinesias are disabling motor complications of long-term dopamine replacement in patients with Parkinson's disease. In recent years, several alternative models have been proposed to explain the pathophysiological mechanisms underlying this hyperkinetic motor disorder. In particular, our group has shed new light on the role of the prefrontal cortex as a key site of interest, demonstrating that, among other areas, the inferior frontal cortex is particularly characterized by altered patterns of anatomical and functional changes. However, how neural activity varies depending on levodopa treatment in patients with dyskinesias and whether the reported prefrontal abnormalities may have a critical role in dyskinesias is debated. To answer these questions we performed independent functional magnetic resonance imaging and repetitive transcranial magnetic stimulation studies. In the first experiment we applied resting state functional magnetic resonance imaging on 12 patients with Parkinson's disease with levodopa-induced dyskinesias and 12 clinically matched patients without dyskinesias, before and after administration of levodopa. Functional connectivity of brain networks in the resting state was assessed in both groups. We chose the right inferior frontal cortex as the seed region given the evidence highlighting the role of this region in motor control. In a second experiment, we applied different forms of repetitive transcranial magnetic stimulation over the right inferior frontal cortex in a new group of dyskinetic patients who were taking a supramaximal dose of levodopa, to verify the clinical relevance of this area in controlling the development of hyperkinetic movements. The resting state functional imaging analysis revealed that in patients with levodopa-induced dyskinesias connectivity of the right inferior frontal cortex was decreased with the left motor cortex and increased with the right putamen when compared to patients without levodopa

  5. 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

  6. Valuation and decision-making in frontal cortex: one or many serial or parallel systems?

    PubMed

    Rushworth, Matthew F S; Kolling, Nils; Sallet, Jérôme; Mars, Rogier B

    2012-12-01

    We evaluate the merits of different conceptualizations of frontal cortex function in value-guided decision-making. According to one view each frontal cortical region is concerned with a different aspect of the process of learning about and evaluating choices and then selecting actions. An alternative view, however, sees sets of decision-making circuits working in parallel within the frontal lobes in order to make different types of decisions. While there is a neural circuit for making choices between pairs of simultaneously presented items in the manner that is frequently assessed in the laboratory, there is also evidence that other frontal lobe circuits have evolved to make other types of choices such as those made during the course of foraging.

  7. Neural dynamics of error processing in medial frontal cortex.

    PubMed

    Mars, Rogier B; Coles, Michael G H; Grol, Meike J; Holroyd, Clay B; Nieuwenhuis, Sander; Hulstijn, Wouter; Toni, Ivan

    2005-12-01

    Adaptive behavior requires an organism to evaluate the outcome of its actions, such that future behavior can be adjusted accordingly and the appropriate response selected. During associative learning, the time at which such evaluative information is available changes as learning progresses, from the delivery of performance feedback early in learning to the execution of the response itself during learned performance. Here, we report a learning-dependent shift in the timing of activation in the rostral cingulate zone of the anterior cingulate cortex from external error feedback to internal error detection. This pattern of activity is seen only in the anterior cingulate, not in the pre-supplementary motor area. The dynamics of these reciprocal changes are consistent with the claim that the rostral cingulate zone is involved in response selection on the basis of the expected outcome of an action. Specifically, these data illustrate how the anterior cingulate receives evaluative information, indicating that an action has not produced the desired result.

  8. Intrinsic functional architecture of the macaque dorsal and ventral lateral frontal cortex.

    PubMed

    Goulas, Alexandros; Stiers, Peter; Hutchison, R Matthew; Everling, Stefan; Petrides, Michael; Margulies, Daniel S

    2017-03-01

    Investigations of the cellular and connectional organization of the lateral frontal cortex (LFC) of the macaque monkey provide indispensable knowledge for generating hypotheses about the human LFC. However, despite numerous investigations, there are still debates on the organization of this brain region. In vivo neuroimaging techniques such as resting-state functional magnetic resonance imaging (fMRI) can be used to define the functional circuitry of brain areas, producing results largely consistent with gold-standard invasive tract-tracing techniques and offering the opportunity for cross-species comparisons within the same modality. Our results using resting-state fMRI from macaque monkeys to uncover the intrinsic functional architecture of the LFC corroborate previous findings and inform current debates. Specifically, within the dorsal LFC, we show that 1) the region along the midline and anterior to the superior arcuate sulcus is divided in two areas separated by the posterior supraprincipal dimple, 2) the cytoarchitectonically defined area 6DC/F2 contains two connectional divisions, and 3) a distinct area occupies the cortex around the spur of the arcuate sulcus, updating what was previously proposed to be the border between dorsal and ventral motor/premotor areas. Within the ventral LFC, the derived parcellation clearly suggests the presence of distinct areas: 1) an area with a somatomotor/orofacial connectional signature (putative area 44), 2) an area with an oculomotor connectional signature (putative frontal eye fields), and 3) premotor areas possibly hosting laryngeal and arm representations. Our results illustrate in detail the intrinsic functional architecture of the macaque LFC, thus providing valuable evidence for debates on its organization.NEW & NOTEWORTHY Resting-state functional MRI is used as a complementary method to invasive techniques to inform current debates on the organization of the macaque lateral frontal cortex. Given that the macaque

  9. Projections from fetal neocortical transplants placed in the frontal neocortex of newborn rats. A Phaseolus vulgaris-leucoagglutinin tracing study.

    PubMed

    Sørensen, J C; Castro, A J; Klausen, B; Zimmer, J

    1992-01-01

    Fetal rat neocortex grafted into lesion cavities made in the newborn rat neocortex can exchange multiple axonal connections with the host brain. Most previous studies demonstrating efferent transplant-to-host brain connections have used fluorescent retrograde tracers injected into the host brain (Castro et al. 1985, 1987; Floeter and Jones 1984; O'Leary and Stanfield 1989). Other studies have used anterograde axonal tracing with either tritium-labelled amino acids impregnating the transplant and its efferents (Floeter and Jones 1985) or horseradish peroxidase injected into the transplants (Chang et al. 1984, 1986). In the present study we used the anterograde axonal tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) to examine in detail the course and termination of the efferent neocortical graft fibers. Twenty-six newborn rats had the right frontal cortex forepaw area removed by vacuum aspiration, while anesthetized by hypothermia. A piece of fetal frontal cortex 14-16 embryonic days old (E14-16) was immediately thereafter placed in the lesion, and the recipient rats allowed to survive for 5-7 months. At this time the rats were reoperated under sodium pentobarbital (Nembutal) anesthesia and the transplants iontophoretically injected with PHA-L. Two weeks later the animals were again anesthetized, perfused, and processed for PHA-L immunocytochemistry and routine histology. Analysis of acetylcholinesterase- (AChE) and Nissl-stained sections showed graft survival in 19 of the 26 animals used in this study. When these 19 brains were processed for PHA-L immunocytochemistry, 5 of them were found with certainty to have the PHA-L injection confined to the transplant. Based on these cases PHA-L-reactive fibers arising from labelled transplant neurons were traced into the ipsilateral host neocortex adjacent to the transplant and found to project through the subcortical white matter to the ipsilateral parietal neocortical area 1, and claustrum. Callosal fibers were traced to

  10. The medial frontal cortex contributes to but does not organize rat exploratory behavior.

    PubMed

    Blankenship, Philip A; Stuebing, Sarah L; Winter, Shawn S; Cheatwood, Joseph L; Benson, James D; Whishaw, Ian Q; Wallace, Douglas G

    2016-11-12

    Animals use multiple strategies to maintain spatial orientation. Dead reckoning is a form of spatial navigation that depends on self-movement cue processing. During dead reckoning, the generation of self-movement cues from a starting position to an animal's current position allow for the estimation of direction and distance to the position movement originated. A network of brain structures has been implicated in dead reckoning. Recent work has provided evidence that the medial frontal cortex may contribute to dead reckoning in this network of brain structures. The current study investigated the organization of rat exploratory behavior subsequent to medial frontal cortex aspiration lesions under light and dark conditions. Disruptions in exploratory behavior associated with medial frontal lesions were consistent with impaired motor coordination, response inhibition, or egocentric reference frame. These processes are necessary for spatial orientation; however, they are not sufficient for self-movement cue processing. Therefore it is possible that the medial frontal cortex provides processing resources that support dead reckoning in other brain structures but does not of itself compute the kinematic details of dead reckoning.

  11. 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

  12. Acute mobile phones exposure affects frontal cortex hemodynamics as evidenced by functional near-infrared spectroscopy.

    PubMed

    Curcio, Giuseppe; Ferrara, Michele; Limongi, Tania; Tempesta, Daniela; Di Sante, Gabriele; De Gennaro, Luigi; Quaresima, Valentina; Ferrari, Marco

    2009-05-01

    This study aimed to evaluate by functional near-infrared spectroscopy (fNIRS), the effects induced by an acute exposure (40 mins) to a GSM (Global System for Mobile Communications) signal emitted by a mobile phone (MP) on the oxygenation of the frontal cortex. Eleven healthy volunteers underwent two sessions (Real and Sham exposure) after a crossover, randomized, double-blind paradigm. The whole procedure lasted 60 mins: 10-mins baseline (Bsl), 40-mins (Exposure), and 10-mins recovery (Post-Exp). Together with frontal hemodynamics, heart rate, objective and subjective vigilance, and self-evaluation of subjective symptoms were also assessed. The fNIRS results showed a slight influence of the GSM signal on frontal cortex, with a linear increase in [HHb] as a function of time in the Real exposure condition (F(4,40)=2.67; P=0.04). No other measure showed any GSM exposure-dependent changes. These results suggest that fNIRS is a convenient tool for safely and noninvasively investigating the cortical activation in MP exposure experimental settings. Given the short-term effects observed in this study, the results should be confirmed on a larger sample size and using a multichannel instrument that allows the investigation of a wider portion of the frontal cortex.

  13. 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

  14. The frontal cortex and the criminal justice system.

    PubMed

    Sapolsky, Robert M

    2004-11-29

    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.

  15. 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.

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

    PubMed Central

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

    2016-01-01

    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

  17. Neuroanatomical correlates of personality in chimpanzees (Pan troglodytes): Associations between personality and frontal cortex.

    PubMed

    Latzman, Robert D; Hecht, Lisa K; Freeman, Hani D; Schapiro, Steven J; Hopkins, William D

    2015-12-01

    Converging empirical data suggests that a set of largely consistent personality traits exist in both human and nonhuman primates; despite these similarities, almost nothing is known concerning the neurobiological basis of these traits in nonhuman primates. The current study examined associations between chimpanzee personality traits and the grey matter volume and asymmetry of various frontal cortex regions in 107 captive chimpanzees. Chimpanzees rated as higher on Openness and Extraversion had greater bilateral grey matter volumes in the anterior cingulate cortex. Further, chimpanzee rated as higher on Dominance had larger grey volumes in the left anterior cingulate cortex and right Prefrontal Cortex (PFC). Finally, apes rated higher on Reactivity/Unpredictability had higher grey matter volumes in the right mesial PFC. All associations survived after applying False Discovery Rate (FDR) thresholds. Results are discussed in terms of current neuroscientific models of personality which suggest that the frontal cortex, and asymmetries in this region, play an important role in the neurobiological foundation of broad dispositional traits.

  18. Neuroanatomical Correlates of Personality in Chimpanzees (Pan troglodytes): Associations between Personality and Frontal Cortex

    PubMed Central

    Latzman, Robert D.; Hecht, Lisa K.; Freeman, Hani D.; Schapiro, Steven J.; Hopkins, William D.

    2015-01-01

    Converging empirical data suggests a set of largely consistent personality traits exist in both human and nonhuman primates; despite these similarities, almost nothing is known concerning the neurobiological basis of these traits in nonhuman primates. The current study examined associations between chimpanzee personality traits and the grey matter volume and asymmetry of various frontal cortex regions in 107 captive chimpanzees. Chimpanzees rated as higher on Openness and Extraversion had greater bilateral grey matter volumes in the anterior cingulate cortex. Further, chimpanzee rated as higher on Dominance had larger grey volumes in the left anterior cingulate cortex and right Prefrontal Cortex (PFC). Finally, apes rated higher on Reactivity/Unpredictability had higher grey matter volumes in the right mesial PFC. All associations survived after applying False Discovery Rate (FDR) thresholds. Results are discussed in terms of current neuroscientific models of personality which suggest that the frontal cortex, and asymmetries in this region, play an important role in the neurobiological foundation of broad dispositional traits. PMID:26311604

  19. [Correlation of evoked potentials in the frontal cortex and hippocampus of cats in emotional stress].

    PubMed

    Vanetsian, G L; Pavlova, I V

    2002-01-01

    Averaged auditory evoked potentials (AEPs) were recorded in symmetric points of the frontal cortex and dorsal hippocampus of cats performing acquired conditioned food-procuring reaction reinforced in 100% cases, urgent transition to 30%-reinforcement, and return to 100%-reinforcement. Emotional stress estimated by a heart rate rise developed during increased food motivation of a cat as well as during change in ordinary food-procuring stereotype. The emotional stress was accompanied by a high positive correlation of cortical and hippocampal AEPs. Decrease in the stress level led to a drop between AEP correlations and appearance of their negative values. In emotional stress, the interactions between the frontal cortex and dorsal hippocampus were asymmetric: right-side correlations were higher.

  20. Conflict awareness dissociates theta-band neural dynamics of the medial frontal and lateral frontal cortex during trial-by-trial cognitive control.

    PubMed

    Jiang, Jun; Zhang, Qinglin; van Gaal, Simon

    2015-08-01

    Recent findings have refuted the common assumption that executive control functions of the prefrontal cortex exclusively operate consciously, suggesting that many, if not all, cognitive processes could potentially operate unconsciously. However, although many cognitive functions can be launched unconsciously, several theoretical models of consciousness assume that there are crucial qualitative differences between conscious and unconscious processes. We hypothesized that the potential benefit of awareness in cognitive control mechanisms might become apparent when high control has to be maintained across time and requires the interaction between a set of distant frontal brain regions. To test this, we extracted oscillatory power dynamics from electroencephalographic data recorded while participants performed a task in which conflict awareness was manipulated by masking the conflict-inducing stimulus. We observed that instantaneous conflict as well as across trial conflict adaptation mechanisms were associated with medial frontal theta-band power modulations, irrespective of conflict awareness. However, and crucially, across-trial conflict adaptation processes reflected in increased theta-band power over dorsolateral frontal cortex were observed after fully conscious conflict only. This suggests that initial conflict detection and subsequent control adaptation by the medial frontal cortex are automatic and unconscious, whereas the routing of information from the medial frontal cortex to the lateral prefrontal cortex is a unique feature of conscious cognitive control.

  1. Large-Scale Meta-Analysis of Human Medial Frontal Cortex Reveals Tripartite Functional Organization

    PubMed Central

    Chang, Luke J.; Banich, Marie T.; Wager, Tor D.; Yarkoni, Tal

    2016-01-01

    The functional organization of human medial frontal cortex (MFC) is a subject of intense study. Using fMRI, the MFC has been associated with diverse psychological processes, including motor function, cognitive control, affect, and social cognition. However, there have been few large-scale efforts to comprehensively map specific psychological functions to subregions of medial frontal anatomy. Here we applied a meta-analytic data-driven approach to nearly 10,000 fMRI studies to identify putatively separable regions of MFC and determine which psychological states preferentially recruit their activation. We identified regions at several spatial scales on the basis of meta-analytic coactivation, revealing three broad functional zones along a rostrocaudal axis composed of 2–4 smaller subregions each. Multivariate classification analyses aimed at identifying the psychological functions most strongly predictive of activity in each region revealed a tripartite division within MFC, with each zone displaying a relatively distinct functional signature. The posterior zone was associated preferentially with motor function, the middle zone with cognitive control, pain, and affect, and the anterior with reward, social processing, and episodic memory. Within each zone, the more fine-grained subregions showed distinct, but subtler, variations in psychological function. These results provide hypotheses about the functional organization of medial prefrontal cortex that can be tested explicitly in future studies. SIGNIFICANCE STATEMENT Activation of medial frontal cortex in fMRI studies is associated with a wide range of psychological states ranging from cognitive control to pain. However, this high rate of activation makes it challenging to determine how these various processes are topologically organized across medial frontal anatomy. We conducted a meta-analysis across nearly 10,000 studies to comprehensively map psychological states to discrete subregions in medial frontal cortex

  2. Evidence for a frontal cortex role in both auditory and somatosensory habituation: A MEG study

    PubMed Central

    Weiland, Barbara J.; Boutros, Nash N.; Moran, John M.; Tepley, Norman; Bowyer, Susan M.

    2008-01-01

    Auditory and somatosensory responses to paired stimuli were investigated for commonality of frontal activation that may be associated with gating using magnetoencephalography (MEG). A paired stimulus paradigm for each sensory evoked study tested right and left hemispheres independently in ten normal controls. MR-FOCUSS, a current density technique, imaged simultaneously active cortical sources. Each subject showed source localization, in the primary auditory or somatosensory cortex, for the respective stimuli following both the first (S1) and second (S2) impulses. Gating ratios for the auditory M50 response, equivalent to the P50 in EEG, were 0.54 ± 0.24 and 0.63 ± 0.52 for the right and left hemispheres. Somatosensory gating ratios were evaluated for early and late latencies as the pulse duration elicits extended response. Early gating ratios for right and left hemispheres were 0.69 ± 0.21 and 0.69 ± 0.41 while late ratios were 0.81 ± 0.41 and 0.80 ± 0.48. Regions of activation in the frontal cortex, beyond the primary auditory or somatosensory cortex, were mapped within 25 ms of peak S1 latencies in 9/10 subjects during auditory stimulus and in 10/10 subjects for somatosensory stimulus. Similar frontal activations were mapped within 25 ms of peak S2 latencies for 75% of auditory responses and for 100% of somatosensory responses. Comparison between modalities showed similar frontal region activations for 17/20 S1 responses and for 13/20 S2 responses. MEG offers a technique for evaluating cross modality gating. The results suggest similar frontal sources are simultaneously active during auditory and somatosensory habituation. PMID:18602839

  3. Cognitive priming in sung and instrumental music: activation of inferior frontal cortex.

    PubMed

    Tillmann, B; Koelsch, S; Escoffier, N; Bigand, E; Lalitte, P; Friederici, A D; von Cramon, D Y

    2006-07-15

    Neural correlates of the processing of musical syntax-like structures have been investigated via expectancy violation due to musically unrelated (i.e., unexpected) events in musical contexts. Previous studies reported the implication of inferior frontal cortex in musical structure processing. However - due to the strong musical manipulations - activations might be explained by sensory deviance detection or repetition priming. Our present study investigated neural correlates of musical structure processing with subtle musical violations in a musical priming paradigm. Instrumental and sung sequences ended on related and less-related musical targets. The material controlled sensory priming components, and differences in target processing required listeners' knowledge on musical structures. Participants were scanned with functional Magnetic Resonance Imaging (fMRI) while performing speeded phoneme and timbre identification judgments on the targets. Behavioral results acquired in the scanner replicated the facilitation effect of related over less-related targets. The blood oxygen level-dependent (BOLD) signal linked to target processing revealed activation of right inferior frontal areas (i.e., inferior frontal gyrus, frontal operculum, anterior insula) that was stronger for less-related than for related targets, and this was independent of the material carrying the musical structures. This outcome points to the implication of inferior frontal cortex in the processing of syntactic relations also for musical material and to its role in the processing and integration of sequential information over time. In addition to inferior frontal activation, increased activation was observed in orbital gyrus, temporal areas (anterior superior temporal gyrus, posterior superior temporal gyrus and sulcus, posterior middle temporal gyrus) and supramarginal gyrus.

  4. 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

  5. Manganese exposure induces α-synuclein aggregation in the frontal cortex of non-human primates.

    PubMed

    Verina, Tatyana; Schneider, Jay S; Guilarte, Tomás R

    2013-03-13

    Aggregation of α-synuclein (α-syn) in the brain is a defining pathological feature of neurodegenerative disorders classified as synucleinopathies. They include Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Occupational and environmental exposure to manganese (Mn) is associated with a neurological syndrome consisting of psychiatric symptoms, cognitive impairment and parkinsonism. In this study, we examined α-syn immunoreactivity in the frontal cortex of Cynomolgus macaques as part of a multidisciplinary assessment of the neurological effects produced by exposure to moderate levels of Mn. We found increased α-syn-positive cells in the gray matter of Mn-exposed animals, typically observed in pyramidal and medium-sized neurons in deep cortical layers. Some of these neurons displayed loss of Nissl staining with α-syn-positive spherical aggregates. In the white matter we also observed α-syn-positive glial cells and in some cases α-syn-positive neurites. These findings suggest that Mn exposure promotes α-syn aggregation in neuronal and glial cells that may ultimately lead to degeneration in the frontal cortex gray and white matter. To our knowledge, this is the first report of Mn-induced neuronal and glial cell α-syn accumulation and aggregation in the frontal cortex of non-human primates.

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

    PubMed

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

    2014-10-01

    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. Copyright © 2014 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.

  7. Comparing development of synaptic proteins in rat visual, somatosensory, and frontal cortex.

    PubMed

    Pinto, Joshua G A; Jones, David G; Murphy, Kathryn M

    2013-01-01

    Two theories have influenced our understanding of cortical development: the integrated network theory, where synaptic development is coordinated across areas; and the cascade theory, where the cortex develops in a wave-like manner from sensory to non-sensory areas. These different views on cortical development raise challenges for current studies aimed at comparing detailed maturation of the connectome among cortical areas. We have taken a different approach to compare synaptic development in rat visual, somatosensory, and frontal cortex by measuring expression of pre-synaptic (synapsin and synaptophysin) proteins that regulate vesicle cycling, and post-synaptic density (PSD-95 and Gephyrin) proteins that anchor excitatory or inhibitory (E-I) receptors. We also compared development of the balances between the pairs of pre- or post-synaptic proteins, and the overall pre- to post-synaptic balance, to address functional maturation and emergence of the E-I balance. We found that development of the individual proteins and the post-synaptic index overlapped among the three cortical areas, but the pre-synaptic index matured later in frontal cortex. Finally, we applied a neuroinformatics approach using principal component analysis and found that three components captured development of the synaptic proteins. The first component accounted for 64% of the variance in protein expression and reflected total protein expression, which overlapped among the three cortical areas. The second component was gephyrin and the E-I balance, it emerged as sequential waves starting in somatosensory, then frontal, and finally visual cortex. The third component was the balance between pre- and post-synaptic proteins, and this followed a different developmental trajectory in somatosensory cortex. Together, these results give the most support to an integrated network of synaptic development, but also highlight more complex patterns of development that vary in timing and end point among the

  8. Acute ethanol and taurine intake affect absolute alpha power in frontal cortex before and after exercise.

    PubMed

    Paulucio, Dailson; da Costa, Bruno M; Santos, Caleb G; Velasques, Bruna; Ribeiro, Pedro; Gongora, Mariana; Cagy, Mauricio; Alvarenga, Renato L; Pompeu, Fernando A M S

    2017-09-14

    Taurine and alcohol has been popularly ingested through energy drinks. Reports from both compounds shows they are active on nervous system but little is known about the acute effect of these substances on the frontal cortex in an exercise approach. The aim of this study was to determine the effects of 0,6mldL(-1) of ethanol (ET), 6g of taurine (TA), and taurine with ethanol (TA+ET) intake on absolute alpha power (AAP) in the frontal region, before and after exercise. Nine participants were recruited, five women (22±3years) and four men (26±5years), for a counterbalanced experimental design. For each treatment, the tests were performed considering three moments: "baseline", "peak" and "post-exercise". In the placebo treatment (PL), the frontal areas showed AAP decrease at the post-exercise. However, in the TA, AAP decreased at peak and increased at post-exercise. In the ET treatment, AAP increased at the peak moment for the left frontal electrodes. In the TA+ET treatment, an AAP increase was observed at peak, and it continued after exercise ended. These substances were able to produce electrocortical activity changes in the frontal regions after a short duration and low intensity exercise. Left and right regions showed different AAP dynamics during peak and post-exercise moments when treatments were compared. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Magnetic sources of the M50 response are localized to frontal cortex.

    PubMed

    Garcia-Rill, E; Moran, K; Garcia, J; Findley, W M; Walton, K; Strotman, B; Llinas, R R

    2008-02-01

    To determine the source localization(s) of the midlatency auditory magnetic response M50, the equivalent of the P50 potential, a sleep state-dependent waveform known to habituate to repetitive stimulation. We used a paired stimulus paradigm at interstimulus intervals of 250, 500 and 1000 ms, and magnetoencephalographic (MEG) recordings were subjected to computational methods for current density reconstruction, blind source separation, time-frequency analysis, and data visualization to characterize evoked dynamics. Each subject showed localization of a source for primary auditory evoked responses in the region of the auditory cortex, usually at a 20-30 ms latency. However, responses at 40-70 ms latency that also decreased following the second stimulus of a pair were not localizable to the auditory cortex, rather showing multiple sources usually including the frontal lobes. The M50 response, which shows habituation to repetitive stimulation, was not localized to the auditory cortex, but showed multiple sources including frontal lobes. These MEG results suggest that sources for the M50 response may represent non-auditory, perhaps arousal-related, diffuse projections to the cortex.

  10. Magnetic sources of the M50 response are localized to frontal cortex

    PubMed Central

    Garcia-Rill, E.; Moran, K.; Garcia, J.; Findley, W. M.; Walton, K.; Strotman, B.; Llinas, R. R.

    2008-01-01

    Objective: To determine the source localization(s) of the midlatency auditory magnetic response M50, the equivalent of the P50 potential, a sleep state-dependent waveform known to habituate to repetitive stimulation. Methods: We used a paired stimulus paradigm at interstimulus intervals of 250, 500 and 1,000 msec, and magnetoencephalographic (MEG) recordings were subjected to computational methods for current density reconstruction, blind source separation, time-frequency analysis, and data visualization to characterize evoked dynamics. Results: Each subject showed localization of a source for primary auditory evoked responses in the region of the auditory cortex, usually at a 20-30 msec latency. However, responses at 40-70 msec latency that also decreased following the second stimulus of a pair, were not localizable to the auditory cortex, rather showing multiple sources usually including the frontal lobes. Conclusions: The M50 response, which shows habituation to repetitive stimulation, was not localized to the auditory cortex, but showed multiple sources including frontal lobes. Significance: These MEG results suggest that sources for the M50 response may represent non-auditory, perhaps arousal-related, diffuse projections to the cortex. PMID:18078782

  11. Complementary roles for primate frontal and parietal cortex in guarding working memory from distractor stimuli.

    PubMed

    Jacob, Simon Nikolas; Nieder, Andreas

    2014-07-02

    Prefrontal cortex (PFC) and posterior parietal cortex are important for maintaining behaviorally relevant information in working memory. Here, we challenge the commonly held view that suppression of distractors by PFC neurons is the main mechanism underlying the filtering of task-irrelevant information. We recorded single-unit activity from PFC and the ventral intraparietal area (VIP) of monkeys trained to resist distracting stimuli in a delayed-match-to-numerosity task. Surprisingly, PFC neurons preferentially encoded distractors during their presentation. Shortly after this interference, however, PFC neurons restored target information, which predicted correct behavioral decisions. In contrast, most VIP neurons only encoded target numerosities throughout the trial. Representation of target information in VIP was the earliest and most reliable neuronal correlate of behavior. Our data suggest that distracting stimuli can be bypassed by storing and retrieving target information, emphasizing active maintenance processes during working memory with complementary functions for frontal and parietal cortex in controlling memory content.

  12. Neuronal reduction in frontal cortex of primates after prenatal alcohol exposure.

    PubMed

    Burke, Mark W; Palmour, Roberta M; Ervin, Frank R; Ptito, Maurice

    2009-01-07

    Children with fetal alcohol spectrum disorders (FASD) show behavioral and intellectual impairments that indicate frontal lobe dysfunction, but the extent of damage to this region has not been clarified by brain imaging studies. This study uses the St Kitts vervet monkey, a species that voluntarily consumes beverage alcohol, to examine the effects of prenatal ethanol exposure. Pregnant vervets were allowed to drink the equivalent of 3-5 standard drinks four times a week during the third trimester. Using unbiased stereology, we estimated neuronal reduction and found significantly fewer cells in the frontal lobes of FASD offspring as well as an increased density of interstitial white matter neurons. These cytoarchitectonic effects are consistent with the behavioral and cognitive changes observed in FASD.

  13. A frontal cortex event-related potential driven by the basal forebrain

    PubMed Central

    Nguyen, David P; Lin, Shih-Chieh

    2014-01-01

    Event-related potentials (ERPs) are widely used in both healthy and neuropsychiatric conditions as physiological indices of cognitive functions. Contrary to the common belief that cognitive ERPs are generated by local activity within the cerebral cortex, here we show that an attention-related ERP in the frontal cortex is correlated with, and likely generated by, subcortical inputs from the basal forebrain (BF). In rats performing an auditory oddball task, both the amplitude and timing of the frontal ERP were coupled with BF neuronal activity in single trials. The local field potentials (LFPs) associated with the frontal ERP, concentrated in deep cortical layers corresponding to the zone of BF input, were similarly coupled with BF activity and consistently triggered by BF electrical stimulation within 5–10 msec. These results highlight the important and previously unrecognized role of long-range subcortical inputs from the BF in the generation of cognitive ERPs. DOI: http://dx.doi.org/10.7554/eLife.02148.001 PMID:24714497

  14. Chronic infusions of GABA into the medial frontal cortex of the rat induce a reversible delayed spatial alternation deficit.

    PubMed

    Di Scala, G; Meneses, S; Brailowsky, S

    1990-10-30

    The effects of bilateral infusions of GABA into the medial frontal cortex of the rat were studied in a delayed spatial alternation task. It was found that GABA (500 mM, 1 microliter/h during 7 days) impaired the performance of the rats in the previously learned task. Upon interruption of the treatment, the animals rapidly recovered normal performance scores. The results show that GABA infusions produce functional deficits similar to those produced by lesions of the frontal cortex. Moreover, the deficits are reversible upon interruption of the treatment. This technique may therefore be a useful tool for studying frontal lobe functions and the involvement of GABAergic mechanisms in cognitive processes.

  15. Gamma-Band Activities in Mouse Frontal and Visual Cortex Induced by Coherent Dot Motion

    PubMed Central

    Han, Hio-Been; Hwang, Eunjin; Lee, Soohyun; Kim, Min-Shik; Choi, Jee Hyun

    2017-01-01

    A key question within systems neuroscience is to understand how the brain encodes spatially and temporally distributed local features and binds these together into one perceptual representation. Previous works in animal and human have shown that changes in neural synchrony occur during the perceptual processing and these changes are distinguished by the emergence of gamma-band oscillations (GBO, 30–80 Hz, centered at 40 Hz). Here, we used the mouse electroencephalogram to investigate how different cortical areas play roles in perceptual processing by assessing their GBO patterns during the visual presentation of coherently/incoherently moving random-dot kinematogram and static dots display. Our results revealed that GBO in the visual cortex were strongly modulated by the moving dots regardless of the existence of a global dot coherence, whereas GBO in frontal cortex were modulated by coherence of the motion. Moreover, concurrent GBO across the multiple cortical area occur more frequently for coherently moving dots. Taken together, these findings of GBO in the mouse frontal and visual cortex are related to the perceptual binding of local features into a globally-coherent representation, suggesting the dynamic interplay across the local/distributed networks of GBO in the global processing of optic flow. PMID:28252109

  16. 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

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

    PubMed Central

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

    2016-01-01

    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

  18. Radioactive 2-DG incorporation patterns in the mesial frontal cortex of task-performing monkeys.

    PubMed

    Matsunami, K; Kawashima, T

    1995-11-01

    The pattern of radioactive 2-deoxy-D-glucose (2-DG) uptake in the rostral mesial cortex was investigated in seven hemispheres of four task-performing monkeys (a delayed-response task performed with a forelimb). A two-dimensional 2-DG map was constructed from frontal sections. Blob-like 2-DG incorporation sites (2-DG active sites) were observed in single frontal sections, e.g., in the anterior cingulate gyrus (CiG) and supplementary and primary motor cortices in the mesial surface, and around the superior precentral sulcus in the premotor area. Blob-like 2-DG incorporation sites were also observed in the medial part of the dorsal frontal cortex near the midline. However, most of these blob-like 2-DG active sites were revealed in fact not to be blobs. They formed rostrocaudally continuous streaks when they were constructed in a two-dimensional map. Streaks fused with one another in some areas, and gave off branches in other areas. These 2-DG uptake patterns were similar between the paired left and right hemispheres of three brains. It is highly probable that these 2-DG active streaks (or blobs) reflected neuronal activity related to somatomotor and/or eye movements, because the 2-DG-labeled areas included motor, premotor, supplementary motor, and possibly part of the supplementary eye fields. It is also probable that this 2-DG incorporation was related to cognitive or memory functions, because neuronal activity related to performance of a delayed-response was reported in the rostral mesial cortex and in the CiG.

  19. Eye-hand coordination during reaching. I. Anatomical relationships between parietal and frontal cortex.

    PubMed

    Marconi, B; Genovesio, A; Battaglia-Mayer, A; Ferraina, S; Squatrito, S; Molinari, M; Lacquaniti, F; Caminiti, R

    2001-06-01

    The anatomical and physiological substrata of eye-hand coordination during reaching were studied through combined anatomical and physiological techniques. The association connections of parietal areas V6A and PEc, and those of dorso-rostral (F7) and dorso-caudal (F2) premotor cortex were studied in monkeys, after physiological characterization of the parietal regions where retrograde tracers were injected. The results show that parieto-occipital area V6A is reciprocally connected with F7, and receives a smaller projection from F2. Local parietal projections to V6A arise from areas MIP and, to a lesser extent, 7m, PEa and PEC: On the contrary, parietal area PEc is strongly and reciprocally connected with the part of F2 located close to the pre-central dimple (pre-CD). Local parietal projections to PEc come from a distributed network, including PEa, MIP, PEci and, to a lesser extent, 7m, V6A, 7a and MST. Premotor area F7 receives parietal projections mainly from 7m and V6A, and local frontal projections mainly from F2. On the contrary, premotor area F2 in the pre-CD zone receives parietal inputs from PEc and, to a lesser extent, PEci, while in the peri-arcuate zone F2 receives parietal projections from PEa and MIP. Local frontal projections to F2 pre-CD mostly stem from F4, and, to a lesser extent, from F7 and F3, and CMAd; those addressed to peri-arcuate zone of F2 arise mainly from F5 and, to a lesser extent, from F7, F4, dorsal (CMAd) and ventral (CMAv) cingulate motor areas, pre-supplementary (F6) and supplementary (F3) motor areas. The distribution of association cells in both frontal and parietal cortex was characterized through a spectral analysis that revealed an arrangement of these cells in the form of bands, composed of cell clusters, or 'columns'. The reciprocal connections linking parietal and frontal cortex might explain the presence of visually related and eye-position signals in premotor cortex, as well as the influence of information about arm

  20. [Effect of Ruiqi tablet on mitochondrion activities in cerebral cortex neurons of fetal rats].

    PubMed

    Zhou, Peiyun; Ge, Wenjin; Li, Duanwu

    2010-06-01

    To explore the effect of Ruiqi tablet on mitochondrion activities in the cerebral cortex neurons of fetal mice. The cerebral cortex of fetal Wistar rats after 16- 17 gestation days were collected and randomized into Ruiqi tablet group and blank control group after 4-5 days' culture. Laser scanning confocal microscope was adopted to determine the changes in the mitochondrion activities of the primary cultured cerebral cortex neurons of fetal rats after addition of Ruiqi tablet solution. Ruiqi tablet can increase the mitochondrion activities of the cerebral cortex neurons. No significant change in the mitochondrion activities of the cerebral cortex neurons was found in the blank control group. Ruiqi tablet can increase the mitochondrion activities of the neurons and it has certain application prospects in treatment of some neurodegenerative diseases such as Alzheimer's disease, vascular dementia, Parkinson's disease and so on.

  1. Dual Immunofluorescence Study of Citrullinated Proteins in Alzheimer Diseased Frontal Cortex

    PubMed Central

    Nicholas, Anthony P.

    2013-01-01

    Deimination is a post-translational modification of proteins in which selected arginine amino acids are enzymatically converted to citrullines. Using dual-color immunofluorescence, the present study is the first to examine the frontal cortex of patients with Alzheimer's disease (AD) versus age-matched controls with an established monoclonal antibody (F95) against peptidyl-citrulline moieties. In AD specimens, a number of new findings were discovered, including evidence for deiminated proteins in extracellular plaques, the walls of large blood vessels, the nuclei of selective neurons immunoreactive for phosphorylated tau and numerous reactive astrocytes concentrated around extracellular plaques, ventricular surfaces and at the interface between the gray and white matter of the cortex. Although the identities of these citrullinated proteins remain largely unknown, the present study adds to the growing number of locations in which deiminated proteins may be found in the brains of patients with AD. PMID:23648390

  2. Dual immunofluorescence study of citrullinated proteins in Alzheimer diseased frontal cortex.

    PubMed

    Nicholas, Anthony P

    2013-06-17

    Deimination is a post-translational modification of proteins in which selected arginine amino acids are enzymatically converted to citrullines. Using dual-color immunofluorescence, the present study is the first to examine the frontal cortex of patients with Alzheimer's disease (AD) versus age-matched controls with an established monoclonal antibody (F95) against peptidyl-citrulline moieties. In AD specimens, a number of new findings were discovered, including evidence for deiminated proteins in extracellular plaques, the walls of large blood vessels, the nuclei of selective neurons immunoreactive for phosphorylated tau and numerous reactive astrocytes concentrated around extracellular plaques, ventricular surfaces and at the interface between the gray and white matter of the cortex. Although the identities of these citrullinated proteins remain largely unknown, the present study adds to the growing number of locations in which deiminated proteins may be found in the brains of patients with AD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  3. Cingulate cortical cells projecting to monkey frontal eye field and primary motor cortex.

    PubMed

    Wang, Yan; Matsuzaka, Yoshiya; Shima, Keisetsu; Tanji, Jun

    2004-07-19

    We compared the distribution of cingulate cortical cells projecting to the frontal eye field (FEF) and primary motor cortex (MI) using a multiple retrograde labeling technique. Two fluorescent tracers were injected into physiologically identified FEF and MI in each monkey. The location of cells projecting to the forelimb area of MI served to identify the rostral (CMAr) and caudal (CMAc) cingulate motor areas. We found two foci of cells projecting to the FEF: rostral (CEFr) and caudal (CEFc) cingulate eye field. The CEFr was located rostral to the CMAr, while the CEFc was located rostro-ventral to the CMAc. Cells projecting to the FEF and MI scarcely overlapped, indicating that each area receives different sets of information from the cingulate cortex.

  4. The performance of human infants on a measure of frontal cortex function, the delayed response task.

    PubMed

    Diamond, A; Doar, B

    1989-04-01

    The Delayed Response task is the best-established marker of frontal lobe function in nonhuman primates. This article reports the developmental progression of human infants on that task. It is proposed that maturation of prefrontal cortex may make possible these age-related improvements in Delayed Response performance. This would suggest the importance of prefrontal cortex functioning very early in life. Twelve infants (6 male, 6 female) were tested longitudinally every two weeks from 6-12 months of age. Another 36 infants (18 male, 18 female) were tested only once: 12 each at 8, 10, and 12 months. We predicted that infants would improve on Delayed Response over these ages because infants' performance on AB improves during this time, and Delayed Response is very similar to AB. The AB task, devised by Piaget, is used to study cognitive development in infants. The ages over which AB performance improves are well established. In both AB and Delayed Response, the subject watches as the experimenter hides a desired object in one of two identical wells. After a brief delay, the subject is allowed to reach. In AB, the object is hidden in the same well on subsequent trials until the subject reaches to the correct well; then side of hiding is reversed and the procedure repeated. In Delayed Response, side of hiding is varied randomly over trials. In the present study of Delayed Response each testing session consisted of 16 trials (eight to the right, eight to the left). We found: (1) the developmental progression for Delayed Response is almost identical to that for AB. (2) Infants of 7 1/2-9 months fail Delayed Response under the same conditions and in the same ways as do monkeys with lesions of dorsolateral prefrontal cortex. It is therefore suggested that AB and Delayed Response require the same cognitive abilities, and that improved performance on these tasks provides an index of maturation of frontal cortex function.

  5. Chronic Social Defeat Stress Modulates Dendritic Spines Structural Plasticity in Adult Mouse Frontal Association Cortex

    PubMed Central

    Shu, Yu

    2017-01-01

    Chronic stress is associated with occurrence of many mental disorders. Previous studies have shown that dendrites and spines of pyramidal neurons of the prefrontal cortex undergo drastic reorganization following chronic stress experience. So the prefrontal cortex is believed to play a key role in response of neural system to chronic stress. However, how stress induces dynamic structural changes in neural circuit of prefrontal cortex remains unknown. In the present study, we examined the effects of chronic social defeat stress on dendritic spine structural plasticity in the mouse frontal association (FrA) cortex in vivo using two-photon microscopy. We found that chronic stress altered spine dynamics in FrA and increased the connectivity in FrA neural circuits. We also found that the changes in spine dynamics in FrA are correlated with the deficit of sucrose preference in defeated mice. Our findings suggest that chronic stress experience leads to adaptive change in neural circuits that may be important for encoding stress experience related memory and anhedonia. PMID:28197343

  6. 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

  7. Effect of Methamphetamine Exposure on Expression of Calcium Binding Proteins in Rat Frontal Cortex and Hippocampus.

    PubMed

    Veerasakul, Siriluk; Thanoi, Samur; Reynolds, Gavin P; Nudmamud-Thanoi, Sutisa

    2016-10-01

    Methamphetamine (METH) is a psychostimulant drug with potent effects on the central nervous system that can cause psychotic symptoms similar to those of schizophrenia. Specific alterations in GABAergic neuronal markers have been reported in schizophrenia and animal models of psychotic illness. The aim of this study was to determine whether there are changes in subpopulations of GABAergic neurons, defined by the presence of calcium binding proteins (CBPs), in animal models of METH abuse. Rats received acute (Binge) doses of 4 × 6 mg/kg, a chronic escalating dose regime (0.1-4 mg/kg over 14 days) or a combination of the two and were compared with a vehicle-administered control group. Brains were taken and sections of frontal cortex (Cg1) and hippocampus (dentate gyrus and CA1-3 regions) underwent immunostaining for three CBPs [parvalbumin (PV), calbindin (CB), and calretinin (CR)]. Significant decreases in PV-immunoreactive (IR) neurons in each METH group and all regions were observed. Smaller METH-induced deficits in CB-IR cells were observed, reaching significance primarily following chronic METH regimes, while CR-IR was significantly reduced only in frontal cortex following chronic administration. These results suggest that METH regimes in rats can induce selective deficits in GABAergic neuronal subtypes similar to those seen in schizophrenia and may underlie the psychosis and/or cognitive impairment that can occur in METH abuse and dependence.

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

    PubMed

    Phoumthipphavong, Victoria; Barthas, Florent; Hassett, Samantha; Kwan, Alex C

    2016-01-01

    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.

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

    PubMed Central

    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

  10. Parietal and Frontal Cortex Encode Stimulus-Specific Mnemonic Representations during Visual Working Memory

    PubMed Central

    Ester, Edward F.; Sprague, Thomas C.; Serences, John T.

    2015-01-01

    Summary Working memory (WM) enables the storage and manipulation of information in an active state. WM storage has long been associated with sustained increases in activation across a network of frontal and parietal cortical regions. However, recent evidence suggests that these regions primarily encode information related to general task goals rather than feature-selective representations of specific memoranda. These goal-related representations are thought to provide top-down feedback that coordinates the representation of fine-grained details in early sensory areas. Here, we test this model using fMRI-based reconstructions of remembered visual details from region-level activation patterns. We could reconstruct high-fidelity representations of a remembered orientation based on activation patterns in occipital visual cortex and in several sub-regions of frontal and parietal cortex, independent of sustained increases in mean activation. These results challenge models of WM that postulate disjoint frontoparietal “top-down control” and posterior sensory “feature storage” networks. PMID:26257053

  11. Parietal and Frontal Cortex Encode Stimulus-Specific Mnemonic Representations during Visual Working Memory.

    PubMed

    Ester, Edward F; Sprague, Thomas C; Serences, John T

    2015-08-19

    Working memory (WM) enables the storage and manipulation of information in an active state. WM storage has long been associated with sustained increases in activation across a network of frontal and parietal cortical regions. However, recent evidence suggests that these regions primarily encode information related to general task goals rather than feature-selective representations of specific memoranda. These goal-related representations are thought to provide top-down feedback that coordinates the representation of fine-grained details in early sensory areas. Here, we test this model using fMRI-based reconstructions of remembered visual details from region-level activation patterns. We could reconstruct high-fidelity representations of a remembered orientation based on activation patterns in occipital visual cortex and in several sub-regions of frontal and parietal cortex, independent of sustained increases in mean activation. These results challenge models of WM that postulate disjoint frontoparietal "top-down control" and posterior sensory "feature storage" networks. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Proteomic analysis reveals differentially expressed proteins in the rat frontal cortex after methamphetamine treatment.

    PubMed

    Faure, J J; Hattingh, S M; Stein, D J; Daniels, W M

    2009-12-01

    Methamphetamine (MA) is an addictive psycho-stimulant and the illicit use of the drug is escalating. In the present study, we examined protein expression profiles in the rat frontal cortex exposed to a total of eight MA injections (1 mg/kg, intraperitoneal) using 2-DE based proteomics. We investigated protein changes occurring in both the cytosolic fraction and the membrane fraction. 2-DE analysis resulted in 62 cytosolic and 44 membrane protein spots that were differentially regulated in the frontal cortex of rats exposed to MA when compared to control animals. Of these spots, 47 cytosolic and 42 membrane proteins were identified respectively, using ESI-Quad-TOF, which included ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCH-L1), beta-synuclein, 78 kDa glucose-regulated protein (GRP 78), gamma-enolase, dihydropyrimidase-related protein 2 (DRP 2), complexin 2 and synapsin II. These proteins are associated with protein degradation, redox regulation, energy metabolism, cellular growth, cytoskeletal modifications and synaptic function. Proteomic research may be useful in exploring the complex underlying molecular mechanisms of MA dependence.

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

    PubMed

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

    2016-05-04

    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.

  14. Cognitive flexibility impairment and reduced frontal cortex BDNF expression in the ouabain model of mania.

    PubMed

    Amodeo, Dionisio A; Grospe, Gena; Zang, Hui; Dwivedi, Yogesh; Ragozzino, Michael E

    2017-03-14

    Central infusion of the Na+/K+-ATPase inhibitor, ouabain in rats serves as an animal model of mania because it leads to hyperactivity, as well as reproduces ion dysregulation and reduced brain-derived neurotrophic factor (BDNF) levels similar to that observed in bipolar disorder. Bipolar disorder is also associated with cognitive inflexibility and working memory deficits. It is unknown whether ouabain treatment in rats leads to similar cognitive flexibility and working memory deficits. The present study examined the effects of an intracerebral ventricular infusion of ouabain in rats on spontaneous alternation, probabilistic reversal learning and BDNF expression levels in the frontal cortex. Ouabain treatment significantly increased locomotor activity, but did not affect alternation performance in a Y-maze. Ouabain treatment selectively impaired reversal learning in a spatial discrimination task using an 80/20 probabilistic reinforcement procedure. The reversal learning deficit in ouabain-treated rats resulted from an impaired ability to maintain a new choice pattern (increased regressive errors). Ouabain treatment also decreased sensitivity to negative feedback during the initial phase of reversal learning. Expression of BDNF mRNA and protein levels was downregulated in the frontal cortex which also negatively correlated with regressive errors. These findings suggest that the ouabain model of mania may be useful in understanding the neuropathophysiology that contributes to cognitive flexibility deficits and test potential treatments to alleviate cognitive deficits in bipolar disorder.

  15. Frontal Cortex Myo-Inositol Is Associated with Sleep and Depression in Adolescents: A Proton Magnetic Resonance Spectroscopy Study.

    PubMed

    Urrila, Anna S; Hakkarainen, Antti; Castaneda, Anu; Paunio, Tiina; Marttunen, Mauri; Lundbom, Nina

    2017-08-10

    This study used proton magnetic resonance spectroscopy (1H MRS) to evaluate the neurochemistry of the frontal cortex in adolescents with symptoms of sleep and depression. Nineteen non-medicated adolescent boys (mean age 16.0 years; 9 clinical cases with depression/sleep symptoms and 10 healthy controls) underwent 1H MRS at 3 T. MR spectra were acquired from the anterior cingulate cortex (ACC), the dorsolateral prefrontal cortex, and frontal white matter. Concentrations of N-acetyl aspartate, total creatine, choline-containing compounds, total glutamine plus glutamate, and myo-inositol (mI) were compared in the 2 subgroups, and correlated with sleep and clinical measures in the total sample. Sleep was assessed with self-report questionnaires and ambulatory polysomnography recordings. Concentrations of mI were lower in both frontal cortical regions among the depressed adolescents than in controls. No statistically significant differences in other metabolite concentrations were observed between the subgroups. Frontal cortex mI concentrations correlated negatively with depression severity, subjective daytime sleepiness, insomnia symptoms, and the level of anxiety, and correlated positively with total sleep time and overall psychosocial functioning. The correlations between mI in the ACC and total sleep time as well as daytime sleepiness remained statistically significant when depression severity was controlled in the analyses. Lower frontal cortex mI may indicate a disturbed second messenger system. Frontal cortical mI may thus be linked to the pathophysiology of depression and concomitant sleep symptoms among maturing adolescents. Short sleep and daytime sleepiness may be associated with frontal cortex mI independently from depression. © 2017 S. Karger AG, Basel.

  16. 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

  17. Drug Addiction and Its Underlying Neurobiological Basis: Neuroimaging Evidence for the Involvement of the Frontal Cortex

    PubMed Central

    Goldstein, Rita Z.; Volkow, Nora D.

    2005-01-01

    Objective Studies of the neurobiological processes underlying drug addiction primarily have focused on limbic subcortical structures. Here the authors evaluated the role of frontal cortical structures in drug addiction. Method An integrated model of drug addiction that encompasses intoxication, bingeing, withdrawal, and craving is proposed. This model and findings from neuroimaging studies on the behavioral, cognitive, and emotional processes that are at the core of drug addiction were used to analyze the involvement of frontal structures in drug addiction. Results The orbitofrontal cortex and the anterior cingulate gyrus, which are regions neuroanatomically connected with limbic structures, are the frontal cortical areas most frequently implicated in drug addiction. They are activated in addicted subjects during intoxication, craving, and bingeing, and they are deactivated during withdrawal. These regions are also involved in higher-order cognitive and motivational functions, such as the ability to track, update, and modulate the salience of a reinforcer as a function of context and expectation and the ability to control and inhibit prepotent responses. Conclusions These results imply that addiction connotes cortically regulated cognitive and emotional processes, which result in the overvaluing of drug reinforcers, the undervaluing of alternative reinforcers, and deficits in inhibitory control for drug responses. These changes in addiction, which the authors call I-RISA (impaired response inhibition and salience attribution), expand the traditional concepts of drug dependence that emphasize limbic-regulated responses to pleasure and reward. PMID:12359667

  18. 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.

  19. Organization of anterior cingulate and frontal cortical projections to the retrosplenial cortex in the rat.

    PubMed

    Shibata, Hideshi; Naito, Jumpei

    2008-01-01

    The retrosplenial cortex (areas 29a-d), which plays an important role in spatial memory and navigation, is known to provide massive projections to frontal association and motor cortices, which are also essential for spatial behavior. The reciprocal projections originating from these frontal cortices to areas 29a-d, however, have been analyzed to only a limited extent. Here, we report an analysis of the anatomical organization of projections from anterior cingulate area 24 and motor and prefrontal cortices to areas 29a-d in the rat, using the axonal transport of cholera toxin B subunit and biotinylated dextran amine. Area 29a receives projections from rostral area 24a, area 24b, the ventral orbital area, and the caudal secondary motor area. Rostral area 29b receives projections from caudal area 24a, whereas caudal area 29b receives projections from rostral area 24a. Area 29b also receives projections from area 24b and the ventral orbital area. Areas 29c and 29d receive projections from areas 24a and 24b and the secondary motor area in a topographic manner such that the rostrocaudal axis of areas 29c and 29d corresponds to the caudorostral axis of areas 24a and 24b and the secondary motor area. Rostral areas 29c and 29d also receive projections from the caudal primary motor area, and area 29d receives projections from the ventral, lateral, and medial orbital areas. These differential frontal cortical projections to each area of the retrosplenial cortex suggest that each area may contribute to different aspects of retrosplenial cortical function such as spatial memory and behavior.

  20. Performance Monitoring Local Field Potentials in the Medial Frontal Cortex of Primates: Anterior Cingulate Cortex

    PubMed Central

    Emeric, Erik E.; Brown, Joshua W.; Leslie, Melanie; Pouget, Pierre; Stuphorn, Veit; Schall, Jeffrey D.

    2009-01-01

    We describe intracranial local field potentials (LFP) recorded in the anterior cingulate cortex (ACC) of macaque monkeys performing a saccade countermanding task. The most prominent feature at ∼70% of sites was greater negative polarity after errors than after rewarded correct trials. This negative polarity was also evoked in unrewarded correct trials. The LFP evoked by the visual target was much less polarized, and the weak presaccadic modulation was insufficient to control the initiation of saccades. When saccades were cancelled, LFP modulation decreased slightly with the magnitude of response conflict that corresponds to the coactivation of gaze-shifting and -holding neurons estimated from the probability of canceling. However, response time adjustments on subsequent trials were not correlated with LFP polarity on individual trials. The results provide clear evidence that error- and feedback-related, but not conflict-related, signals are carried by the LFP in the macaque ACC. Finding performance monitoring field potentials in the ACC of macaque monkeys establishes a bridge between event-related potential and functional brain-imaging studies in humans and neurophysiology studies in non-human primates. PMID:18077665

  1. 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

  2. Functional and structural remodeling of glutamate synapses in prefrontal and frontal cortex induced by behavioral stress.

    PubMed

    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.

  3. 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

  4. [Functional asymmetry of the frontal cortex and lateral hypothalamus of cats during food instrumental conditioning].

    PubMed

    Vanetsiian, G L; Pavlova, I V

    2003-01-01

    The synchronism and latency of auditory evoked potentials (EP) recorded in symmetric points of the frontal cortex and lateral hypothalamus of cats were measured at different stages of instrumental food conditioning and after the urgent transition to 30% reinforcement. Correlation coefficients between EPs in the cortex and hypothalamus were high (with left-side dominance) at the beginning of the experiments, when food motivation was high, and during the whole experiments in cases of high-probability of conditioned performance. Analysis of early positive P55-80 EP component showed that at all conditioning stages the peak latency of this component was shorter in the left cortical areas than in symmetrical points, whereas in the hypothalamus the shorter latency at the left side was observed at the stage of unstable conditioned reflex, and at the stage of stable reflex the latency of the studied component was shorter at the right side. During transition to 30% reinforcement, the latency was also shorter in the right hypothalamus. It is suggested that the high left-side correlation between the hypothalamus and cortex was associated with motivational and motor component of behavior rather than reflected the emotional stress induced by transition to another stereotype of food reinforcement (30%).

  5. 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. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. A proton magnetic resonance spectroscopic study in autism spectrum disorders: amygdala and orbito-frontal cortex.

    PubMed

    Mori, Kenji; Toda, Yoshihiro; Ito, Hiromichi; Mori, Tatsuo; Goji, Aya; Fujii, Emiko; Miyazaki, Masahito; Harada, Masafumi; Kagami, Shoji

    2013-02-01

    We previously reported neural dysfunction in the anterior cingulate cortex and dorsolateral prefrontal cortex in autistic patients using proton magnetic resonance spectroscopy ((1)H-MRS). In this investigation, we measured chemical metabolites in the left amygdala and the bilateral orbito-frontal cortex (OFC), which are the main components of the social brain. We also examined the association between these metabolic findings and social abilities in subjects with autism. The study group included 77 autistic patients (3-6years old; mean age 4.1; 57 boys and 20 girls). The control subjects were 31 children (3-6years old; mean age 4.0; 23 boys and 8 girls). Conventional proton MR spectra were obtained using the STEAM sequence with parameters of TR=5 sec and TE=15 msec by a 1.5-tesla clinical MRI system. We analyzed the concentrations of N-acetylaspartate (NAA), creatine/phosphocreatine (Cr), and choline-containing compounds (Cho) using LCModel (Ver. 6.1). The concentrations of NAA in the left amygdala and the bilateral OFC in autistic patients were significantly decreased compared to those in the control group. In the autistic patients, the NAA concentrations in these regions correlated with their social quotient. These findings suggest the presence of neuronal dysfunction in the amygdala and OFC in autism. Dysfunction in the amygdala and OFC may contribute to the pathogenesis of autism.

  7. Sertraline, a selective serotonin reuptake inhibitor modulates extracellular noradrenaline in the rat frontal cortex.

    PubMed

    Thomas, D N; Nutt, D J; Holman, R B

    1998-01-01

    The selective action of selective serotonergic reuptake inhibitors (SSRIs) on 5-hydroxytryptamine (5-HT) neurotransmission underlies the therapeutic effectiveness of this class of drugs. Yet there is increasing evidence that changes in extracellular 5-HT content may result in changes in the regulation of other neurotransmitter systems. The present study examines the effects of acute and chronic administration of the SSRI sertraline on release of endogenous noradrenaline (NA) in the frontal cortex and hippocampus of the rat using in vivo microdialysis. Acute administration of sertraline did not significantly alter NA release in either the cortex or the hippocampus. However, 24 h after chronic (14 days) administration of the drug (10 mg/kg i.p. once daily), NA release in the cortex but not hippocampus was significantly enhanced. The lack of an effect on NA release following a challenge with the alpha2-antagonist idazoxan suggests that chronic drug treatment has reduced the sensitivity of cortical pre-synaptic alpha2-adrenoceptors, activation of which would normally inhibit further NA release. The possible mechanisms underlying the regional specificity of the effect of chronic and not acute sertraline administration and the implications of these results for our understanding of depression are discussed.

  8. Structural changes in the temporal lobe and piriform cortex in frontal lobe epilepsy.

    PubMed

    Centeno, M; Vollmar, C; Stretton, J; Symms, M R; Thompson, P J; Richardson, M P; O'Muircheartaigh, J; Duncan, J S; Koepp, M J

    2014-07-01

    Neuronal networks involved in seizure generation, maintenance and spread of epileptic activity comprise cortico-subcortical circuits. Although epileptic foci vary in location across focal epilepsy syndromes, there is evidence for common structures in the epileptogenic networks. We recently reported evidence from functional neuroimaging for a unique area in the piriform cortex, common to focal epilepsies in humans, which might play a role in modulating seizure activity. In this study, we aimed to identify common areas of structural abnormalities in patients with frontal lobe epilepsy (FLE). T1-weighted MRI scans of 43 FLE patients and 25 healthy controls were analysed using voxel based morphometry. Differences in regional grey matter volume were examined across the whole brain, and correlated with age at epilepsy onset, duration and frequency of seizures. We detected areas of increased grey matter volume in the piriform cortex, amygdala and parahippocampal gyrus bilaterally, as well as left mid temporal gyrus of patients relative to controls, which did not correlate with any of the clinical variables tested. No common areas of atrophy were detected across the FLE group. Structural abnormalities within the piriform cortex and adjacent structures of patients with FLE provide further evidence for the involvement of this area in the epileptogenic network of focal epilepsies. Lack of correlation with duration or age of onset of epilepsy suggests that this area of abnormality is not a consequence of seizure activity. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Calbindin D-28k and parvalbumin immunoreactivity in the frontal cortex in patients with frontal lobe dementia of non-Alzheimer type associated with amyotrophic lateral sclerosis.

    PubMed Central

    Ferrer, I; Tuñón, T; Serrano, M T; Casas, R; Alcántara, S; Zújar, M J; Rivera, R M

    1993-01-01

    The morphology and distribution of local-circuit neurons (interneurons) were examined, by calbindin D-28k and parvalbumin immunocytochemistry, in the frontal cortex (area 8) in two patients with frontal lobe dementia of non-Alzheimer type associated with classical amyotrophic lateral sclerosis (ALS), and in seven normal cases. The density of calbindin D-28k immunoreactive cells was dramatically reduced in ALS patients, but the density of parvalbumin-immunoreactive neurons was preserved. Decreased density of calbindin D-28k-immunoreactive neurons, which are mainly located in the upper cortical layers, may interfere with the normal processing of cortico-cortical connections, whereas integrity of parvalbumin-immunoreactive cells may be associated with the preservation of the major inhibitory intracortical circuits in patients with frontal lobe dementia. Images PMID:8459241

  10. Frontal Motor Cortex Activity During Reactive Control Is Associated With Past Suicidal Behavior in Recent-Onset Schizophrenia.

    PubMed

    Minzenberg, Michael J; Lesh, Tyler; Niendam, Tara; Yoon, Jong H; Cheng, Yaoan; Rhoades, Remy N; Carter, Cameron S

    2015-01-01

    Suicide is prevalent in schizophrenia (SZ), yet the neural system functions that confer suicide risk remain obscure. Circuits operated by the prefrontal cortex (PFC) are altered in SZ, including those that support reactive control, and PFC changes are observed in postmortem studies of heterogeneous suicide victims. We tested whether history of suicide attempt is associated with altered frontal motor cortex activity during reactive control processes. We evaluated 17 patients with recent onset of DSM-IV-TR-defined SZ using the Columbia Suicide Severity Rating Scale and functional magnetic resonance imaging during Stroop task performance. Group-level regression models relating past suicidal behavior to frontal activation controlled for depression, psychosis, and impulsivity. Past suicidal behavior was associated with relatively higher activation in the left-hemisphere supplementary motor area (SMA), pre-SMA, premotor cortex, and dorsolateral PFC, all ipsilateral to the active primary motor cortex. This study provides unique evidence that suicidal behavior in patients with recent-onset SZ directly relates to frontal motor cortex activity during reactive control, in a pattern reciprocal to the relationship with proactive control found previously. Further work should address how frontal-based control functions change with risk over time, and their potential utility as a biomarker for interventions to mitigate suicide risk in SZ.

  11. Distinct causal influences of parietal versus frontal areas on human visual cortex: evidence from concurrent TMS-fMRI.

    PubMed

    Ruff, Christian C; Bestmann, Sven; Blankenburg, Felix; Bjoertomt, Otto; Josephs, Oliver; Weiskopf, Nikolaus; Deichmann, Ralf; Driver, Jon

    2008-04-01

    It has often been proposed that regions of the human parietal and/or frontal lobe may modulate activity in visual cortex, for example, during selective attention or saccade preparation. However, direct evidence for such causal claims is largely missing in human studies, and it remains unclear to what degree the putative roles of parietal and frontal regions in modulating visual cortex may differ. Here we used transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) concurrently, to show that stimulating right human intraparietal sulcus (IPS, at a site previously implicated in attention) elicits a pattern of activity changes in visual cortex that strongly depends on current visual context. Increased intensity of IPS TMS affected the blood oxygen level-dependent (BOLD) signal in V5/MT+ only when moving stimuli were present to drive this visual region, whereas TMS-elicited BOLD signal changes were observed in areas V1-V4 only during the absence of visual input. These influences of IPS TMS upon remote visual cortex differed significantly from corresponding effects of frontal (eye field) TMS, in terms of how they related to current visual input and their spatial topography for retinotopic areas V1-V4. Our results show directly that parietal and frontal regions can indeed have distinct patterns of causal influence upon functional activity in human visual cortex.

  12. Agreement between functional connectivity and cortical thickness-driven correlation maps of the medial frontal cortex

    PubMed Central

    Park, Hyunjin; Park, Yeong-Hun; Cha, Jungho; Seo, Sang Won; Na, Duk L.

    2017-01-01

    Parcellation of the human cortex has important implications in neuroscience. Parcellation is often a crucial requirement before meaningful regional analysis can occur. The human cortex can be parcellated into distinct regions based on structural features, such as gyri and sulci. Brain network patterns in a given region with respect to its neighbors, known as connectional fingerprints, can be used to parcellate the cortex. Distinct imaging modalities might provide complementary information for brain parcellation. Here, we established functional connectivity with time series data from functional MRI (fMRI) combined with a correlation map of cortical thickness obtained from T1-weighted MRI. We aimed to extend the previous study, which parcellated the medial frontal cortex (MFC) using functional connectivity, and to test the value of additional information regarding cortical thickness. Two types of network information were used to parcellate the MFC into two sub-regions with spectral and Ward’s clustering approaches. The MFC region was defined using manual delineation based on in-house data (n = 12). Parcellation was applied to independent large-scale data obtained from the Human Connectome Project (HCP, n = 248). Agreement between parcellation using fMRI- and thickness-driven connectivity yielded dice coefficient overlaps of 0.74 (Ward’s clustering) and 0.54 (spectral clustering). We also explored whole brain connectivity using the MFC sub-regions as seed regions based on these two types of information. The results of whole brain connectivity analyses were also consistent for both types of information. We observed that an inter-regional correlation map derived from cortical thickness strongly reflected the underlying functional connectivity of MFC region. PMID:28328993

  13. Overpressure blast injury-induced oxidative stress and neuroinflammation response in rat frontal cortex and cerebellum.

    PubMed

    Toklu, Hale Z; Yang, Zhihui; Oktay, Sehkar; Sakarya, Yasemin; Kirichenko, Nataliya; Matheny, Michael K; Muller-Delp, Judy; Strang, Kevin; Scarpace, Philip J; Wang, Kevin K W; Tümer, Nihal

    2017-04-15

    Overpressure blast-wave induced brain injury (OBI) and its long-term neurological outcome pose significant concerns for military personnel. Our aim is to investigate the mechanism of injury due to OBI. Rats were divided into 3 groups: (1) Control, (2) OBI (exposed 30psi peak pressure, 2-2.5ms), (3) Repeated OBI (r-OBI) (three exposures over one-week period). Lung and brain (cortex and cerebellum) tissues were collected at 24h post injury. The neurological examination score was worse in OBI and r-OBI (4.2±0.6 and 3.7±0.5, respectively) versus controls (0.7±0.2). A significant positive correlation between lung and brain edema was found. Malondialdehyde (index for lipid peroxidation), significantly increased in OBI and r-OBI groups in cortex (p<0.05) and cerebellum (p<0.01-0.001). The glutathione (endogenous antioxidant) level decreased in cortex (p<0.01) and cerebellum (p<0.05) of r-OBI group when compared with the controls. Myeloperoxidase activity indicating neutrophil infiltration, was significantly (p<0.01-0.05) elevated in r-OBI. Additionally, tissue thromboplastin activity, a coagulation marker, was elevated, indicating a tendency to bleed. NGF and NF-κB proteins along with Iba-1 and GFAP immunoreactivity significantly augmented in the frontal cortex demonstrating microglial activation. Serum biomarkers of injury, NSE, TNF-alpha and leptin, were also elevated. OBI triggers both inflammation and oxidative injury in the brain. This data in conjunction with our previous observations suggests that OBI triggers a cascade of events beginning with impaired cerebral vascular function leading to ischemia and chronic neurological consequences. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Reward-Modulated Response Inhibition, Cognitive Shifting, and the Orbital Frontal Cortex in Early Adolescence

    PubMed Central

    Zhai, Zu Wei; Pajtek, Stefan; Luna, Beatriz; Geier, Charles F.; Ridenour, Ty A.; Clark, Duncan B.

    2014-01-01

    Immaturities in cognitive shifting are associated with adolescent risk behaviors. The orbital frontal cortex (OFC) regulates reward processing and response inhibition. This study tested the relationship between cognitive shifting, OFC activity, and reward-modulated response inhibition in young adolescents. An fMRI antisaccade (AS) paradigm examined the effects of reward conditions on inhibitory response and OFC processing. A validated self-report inventory assessed cognitive shifting. Compared to neutral, reward trials showed better AS performance and increased OFC activation. Cognitive shifting positively associated with AS performance in reward and neutral trials. Poorer cognitive shifting predicted greater OFC activation. Results indicate lower OFC efficiency, as greater activation to achieve correct performance, underlies cognitive shifting problems. These neurocognitive impairments are relevant for understanding adolescent risk behaviors. PMID:26755891

  15. Effect of aging on lazabemide binding, monoamine oxidase activity and monoamine metabolites in human frontal cortex.

    PubMed

    Galva, M D; Bondiolotti, G P; Olasmaa, M; Picotti, G B

    1995-01-01

    Age-related modifications of monoamine oxidase-A and -B (MAO-A and MAO-B) and amine metabolite concentrations were studied in human frontal cortex taken postmortem from 22 subjects of various ages (21-75 years). Qualitative and quantitative analysis for MAO-B was provided by kinetic studies with a specific radioligand, [3H]lazabemide. The data demonstrated a significant (P < 0.05) positive correlation between the density of [3H]lazabemide binding sites (Bmax) and age of the subject, without showing an apparent modification in the dissociation constant (KD) of the radioligand. In parallel experiments, MAO-B but not MAO-A activity was shown to correlate with age (P < 0.05). The concentrations of the amine metabolites 4-hydroxy-3-methoxyphenylacetic acid (HVA), 5-hydroxyindole-3-acetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), 4-hydroxy-3-methoxyphenylglycol (MHPG) and 3,4-dihydroxyphenylglycol (DHPG) were all devoid of a correlation with age. Neither did the concentrations of these metabolites relate to the respective subject's MAO-B enzymatic activity nor to [3H]lazabemide Bmax. A correlation, though rather weak, was obtained between MAO-A activity and MHPG concentration (P = 0.045). The MAO-A and -B enzyme characteristics in subjects who had committed suicide (n = 9) did not differ from those of subjects deceased for other causes (n = 13). Among the measured monoamine metabolites the concentrations of DOPAC and HVA were higher in the suicide versus control group (P < 0.05). The present data confirm in a direct manner that the increase in MAO-B activity in aging brain is due to an enhancement of the number of active sites of the enzyme and not through modifications of its kinetic characteristics. Furthermore, that neither the characteristics nor the activity of the enzyme are changed in the frontal cortex of suicide victims compared to control subjects.

  16. Loss of Sleep Affects the Ultrastructure of Pyramidal Neurons in the Adolescent Mouse Frontal Cortex

    PubMed Central

    de Vivo, Luisa; Nelson, Aaron B.; Bellesi, Michele; Noguti, Juliana; Tononi, Giulio; Cirelli, Chiara

    2016-01-01

    Study Objective: The adolescent brain may be uniquely affected by acute sleep deprivation (ASD) and chronic sleep restriction (CSR), but direct evidence is lacking. We used electron microscopy to examine how ASD and CSR affect pyramidal neurons in the frontal cortex of adolescent mice, focusing on mitochondria, endosomes, and lysosomes that together perform most basic cellular functions, from nutrient intake to prevention of cellular stress. Methods: Adolescent (1-mo-old) mice slept (S) or were sleep deprived (ASD, with novel objects and running wheels) during the first 6–8 h of the light period, chronically sleep restricted (CSR) for > 4 days (using novel objects, running wheels, social interaction, forced locomotion, caffeinated water), or allowed to recover sleep (RS) for ∼32 h after CSR. Ultrastructural analysis of 350 pyramidal neurons was performed (S = 82; ASD = 86; CSR = 103; RS = 79; 4 to 5 mice/group). Results: Several ultrastructural parameters differed in S versus ASD, S versus CSR, CSR versus RS, and S versus RS, although the different methods used to enforce wake may have contributed to some of the differences between short and long sleep loss. Differences included larger cytoplasmic area occupied by mitochondria in CSR versus S, and higher number of secondary lysosomes in CSR versus S and RS. We also found that sleep loss may unmask interindividual differences not obvious during baseline sleep. Moreover, using a combination of 11 ultrastructural parameters, we could predict in up to 80% of cases whether sleep or wake occurred at the single cell level. Conclusions: Ultrastructural analysis may be a powerful tool to identify which cellular organelles, and thus which cellular functions, are most affected by sleep and sleep loss. Citation: de Vivo L, Nelson AB, Bellesi M, Noguti J, Tononi G, Cirelli C. Loss of sleep affects the ultrastructure of pyramidal neurons in the adolescent mouse frontal cortex. SLEEP 2016;39(4):861–874. PMID:26715225

  17. Midline Frontal Cortex Low-Frequency Activity Drives Subthalamic Nucleus Oscillations during Conflict

    PubMed Central

    Zavala, Baltazar A.; Tan, Huiling; Little, Simon; Ashkan, Keyoumars; Hariz, Marwan; Foltynie, Thomas; Zrinzo, Ludvic; Zaghloul, Kareem A.

    2014-01-01

    Making the right decision from conflicting information takes time. Recent computational, electrophysiological, and clinical studies have implicated two brain areas as being crucial in assuring sufficient time is taken for decision-making under conditions of conflict: the medial prefrontal cortex and the subthalamic nucleus (STN). Both structures exhibit an elevation of activity at low frequencies (<10 Hz) during conflict that correlates with the amount of time taken to respond. This suggests that the two sites could become functionally coupled during conflict. To establish the nature of this interaction we recorded from deep-brain stimulation electrodes implanted bilaterally in the STN of 13 Parkinson's disease patients while they performed a sensory integration task involving randomly moving dots. By gradually increasing the number of dots moving coherently in one direction, we were able to determine changes in the STN associated with response execution. Furthermore, by occasionally having 10% of the dots move in the opposite direction as the majority, we were able to identify an independent increase in STN theta-delta activity triggered by conflict. Crucially, simultaneous midline frontal electroencephalographic recordings revealed an increase in the theta-delta band coherence between the two structures that was specific to high-conflict trials. Activity over the midline frontal cortex was Granger causal to that in STN. These results establish the cortico-subcortical circuit enabling successful choices to be made under conditions of conflict and provide support for the hypothesis that the brain uses frequency-specific channels of communication to convey behaviorally relevant information. PMID:24849364

  18. Midline frontal cortex low-frequency activity drives subthalamic nucleus oscillations during conflict.

    PubMed

    Zavala, Baltazar A; Tan, Huiling; Little, Simon; Ashkan, Keyoumars; Hariz, Marwan; Foltynie, Thomas; Zrinzo, Ludvic; Zaghloul, Kareem A; Brown, Peter

    2014-05-21

    Making the right decision from conflicting information takes time. Recent computational, electrophysiological, and clinical studies have implicated two brain areas as being crucial in assuring sufficient time is taken for decision-making under conditions of conflict: the medial prefrontal cortex and the subthalamic nucleus (STN). Both structures exhibit an elevation of activity at low frequencies (<10 Hz) during conflict that correlates with the amount of time taken to respond. This suggests that the two sites could become functionally coupled during conflict. To establish the nature of this interaction we recorded from deep-brain stimulation electrodes implanted bilaterally in the STN of 13 Parkinson's disease patients while they performed a sensory integration task involving randomly moving dots. By gradually increasing the number of dots moving coherently in one direction, we were able to determine changes in the STN associated with response execution. Furthermore, by occasionally having 10% of the dots move in the opposite direction as the majority, we were able to identify an independent increase in STN theta-delta activity triggered by conflict. Crucially, simultaneous midline frontal electroencephalographic recordings revealed an increase in the theta-delta band coherence between the two structures that was specific to high-conflict trials. Activity over the midline frontal cortex was Granger causal to that in STN. These results establish the cortico-subcortical circuit enabling successful choices to be made under conditions of conflict and provide support for the hypothesis that the brain uses frequency-specific channels of communication to convey behaviorally relevant information. Copyright © 2014 Zavala et al.

  19. 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.

  20. 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

  1. Effects of (-)-epicatechin on frontal cortex DAPC and dysbindin of the mdx mice.

    PubMed

    Estrada-Mena, Francisco J; Rodriguez, Alonso; Mendoza-Lorenzo, Patricia; Neri-Gomez, Teresa; Manjarrez-Gutierrez, Gabriel; Perez-Ortiz, Andric C; Ordonez-Razo, Rosa; Ceballos, Guillermo; Villarreal, Francisco; Ramirez-Sanchez, Israel

    2017-08-31

    Multiple components of the dystrophin-associated protein complex (DAPC) are expressed in numerous tissues including the brain. Members of the DAPC and dysbindin are abnormally expressed in the brain of Duchenne Muscular Dystrophy (DMD) patients, which has been associated with cognitive impairments. However, little is known about the expression pattern of individual members of the DAPC in animal models of DMD and their relationship with dysbindin. Ten mdx mice were randomly allocated into a control and intervention group [(-)-epicatechin (Epi) 1mg/kg/day for four weeks] and results compared to a wild-type mice. After sacrifice, brain pre-frontal cortices were collected for Western blotting and immunoprecipitation assays, and sagittal sections processed for immunohistochemistry. Epi promotes a partial recovery of DAPC members [α1-Syntrophin, sarcoglycans (SG), dystrophin 71 (Dp71)], dysbindin, and utrophin protein levels. Epi also appears to restore the association of DAPC between dysbindin, and utrophin with Dp71 and ε-SG. Co-immunostaining evidence increased protein levels of dysbindin, dystrophin, and ε-SG and their colocalization. Altogether, results suggest that Epi is capable of restoring pre-frontal cortex DAPC and dysbindin levels of mdx mice towards that of healthy brains. The functional implications of such studies warrant further investigation. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. The morphology of midcingulate cortex predicts frontal-midline theta neurofeedback success

    PubMed Central

    Enriquez-Geppert, Stefanie; Huster, René J.; Scharfenort, Robert; Mokom, Zacharais N.; Vosskuhl, Johannes; Figge, Christian; Zimmermann, Jörg; Herrmann, Christoph S.

    2013-01-01

    Humans differ in their ability to learn how to control their own brain activity by neurofeedback. However, neural mechanisms underlying these inter-individual differences, which may determine training success and associated cognitive enhancement, are not well-understood. Here, it is asked whether neurofeedback success of frontal-midline (fm) theta, an oscillation related to higher cognitive functions, could be predicted by the morphology of brain structures known to be critically involved in fm-theta generation. Nineteen young, right-handed participants underwent magnetic resonance imaging of T1-weighted brain images, and took part in an individualized, eight-session neurofeedback training in order to learn how to enhance activity in their fm-theta frequency band. Initial training success, measured at the second training session, was correlated with the final outcome measure. We found that the inferior, superior, and middle frontal cortices were not associated with training success. However, volume of the midcingulate cortex as well as volume and concentration of the underlying white matter structures act as predictor variables for the general responsiveness to training. These findings suggest a neuroanatomical foundation for the ability to learn to control one's own brain activity. PMID:23950741

  3. The morphology of midcingulate cortex predicts frontal-midline theta neurofeedback success.

    PubMed

    Enriquez-Geppert, Stefanie; Huster, René J; Scharfenort, Robert; Mokom, Zacharais N; Vosskuhl, Johannes; Figge, Christian; Zimmermann, Jörg; Herrmann, Christoph S

    2013-01-01

    Humans differ in their ability to learn how to control their own brain activity by neurofeedback. However, neural mechanisms underlying these inter-individual differences, which may determine training success and associated cognitive enhancement, are not well-understood. Here, it is asked whether neurofeedback success of frontal-midline (fm) theta, an oscillation related to higher cognitive functions, could be predicted by the morphology of brain structures known to be critically involved in fm-theta generation. Nineteen young, right-handed participants underwent magnetic resonance imaging of T1-weighted brain images, and took part in an individualized, eight-session neurofeedback training in order to learn how to enhance activity in their fm-theta frequency band. Initial training success, measured at the second training session, was correlated with the final outcome measure. We found that the inferior, superior, and middle frontal cortices were not associated with training success. However, volume of the midcingulate cortex as well as volume and concentration of the underlying white matter structures act as predictor variables for the general responsiveness to training. These findings suggest a neuroanatomical foundation for the ability to learn to control one's own brain activity.

  4. 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

  5. Chronic Ritalin administration during adulthood increases serotonin pool in rat medial frontal cortex.

    PubMed

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

    2013-01-01

    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. 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. 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. Our findings demonstrated both short- and long-term effects of Ritalin on frontal serotonergic system after withdrawal period.

  6. 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. Copyright © 2012 Elsevier Inc. All rights reserved.

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

    PubMed

    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.

  8. 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

  9. Placental estrogen suppresses cyclin D1 expression in the nonhuman primate fetal adrenal cortex.

    PubMed

    Dumitrescu, Adina; Aberdeen, Graham W; Pepe, Gerald J; Albrecht, Eugene D

    2014-12-01

    We have previously shown that estrogen selectively suppresses growth of the fetal zone of the baboon fetal adrenal cortex, which produces the C19-steroid precursors, eg, dehydroepiandrosterone sulfate, which are aromatized to estrogen within the placenta. In the present study, we determined whether fetal adrenal expression of cell cycle regulators are altered by estrogen and thus provide a mechanism by which estrogen regulates fetal adrenocortical development. Cyclin D1 mRNA levels in the whole fetal adrenal were increased 50% (P < .05), and the number of cells in the fetal adrenal definitive zone expressing cyclin D1 protein was increased 2.5-fold (P < .05), whereas the total number of cells in the fetal zone and fetal serum dehydroepiandrosterone sulfate levels were elevated 2-fold (P < .05) near term in baboons in which fetal serum estradiol levels were decreased by 95% (P < .05) after maternal administration of the aromatase inhibitor letrozole and restored to normal by concomitant administration of letrozole plus estradiol throughout second half of gestation. However, fetal adrenocortical expression of cyclin D2, the cyclin-dependent kinase (Cdk)-2, Cdk4, and Cdk6, and Cdk regulatory proteins p27(Kip1) and p57(Kip2) were not changed by letrozole or letrozole plus estradiol administration. We suggest that estrogen controls the growth of the fetal zone of the fetal adrenal by down-regulating cyclin D1 expression and thus proliferation of progenitor cells within the definitive zone that migrate to the fetal zone. We propose that estrogen restrains growth and function of the fetal zone via cyclin D1 to maintain estrogen levels in a physiological range during primate pregnancy.

  10. Placental Estrogen Suppresses Cyclin D1 Expression in the Nonhuman Primate Fetal Adrenal Cortex*

    PubMed Central

    Dumitrescu, Adina; Aberdeen, Graham W.; Pepe, Gerald J.

    2014-01-01

    We have previously shown that estrogen selectively suppresses growth of the fetal zone of the baboon fetal adrenal cortex, which produces the C19-steroid precursors, eg, dehydroepiandrosterone sulfate, which are aromatized to estrogen within the placenta. In the present study, we determined whether fetal adrenal expression of cell cycle regulators are altered by estrogen and thus provide a mechanism by which estrogen regulates fetal adrenocortical development. Cyclin D1 mRNA levels in the whole fetal adrenal were increased 50% (P < .05), and the number of cells in the fetal adrenal definitive zone expressing cyclin D1 protein was increased 2.5-fold (P < .05), whereas the total number of cells in the fetal zone and fetal serum dehydroepiandrosterone sulfate levels were elevated 2-fold (P < .05) near term in baboons in which fetal serum estradiol levels were decreased by 95% (P < .05) after maternal administration of the aromatase inhibitor letrozole and restored to normal by concomitant administration of letrozole plus estradiol throughout second half of gestation. However, fetal adrenocortical expression of cyclin D2, the cyclin-dependent kinase (Cdk)-2, Cdk4, and Cdk6, and Cdk regulatory proteins p27Kip1 and p57Kip2 were not changed by letrozole or letrozole plus estradiol administration. We suggest that estrogen controls the growth of the fetal zone of the fetal adrenal by down-regulating cyclin D1 expression and thus proliferation of progenitor cells within the definitive zone that migrate to the fetal zone. We propose that estrogen restrains growth and function of the fetal zone via cyclin D1 to maintain estrogen levels in a physiological range during primate pregnancy. PMID:25247468

  11. Sensory-Biased and Multiple-Demand Processing in Human Lateral Frontal Cortex.

    PubMed

    Noyce, Abigail L; Cestero, Nishmar; Michalka, Samantha W; Shinn-Cunningham, Barbara G; Somers, David C

    2017-09-06

    The functionality of much of human lateral frontal cortex (LFC) has been characterized as "multiple demand" (MD) as these regions appear to support a broad range of cognitive tasks. In contrast to this domain-general account, recent evidence indicates that portions of LFC are consistently selective for sensory modality. Michalka et al. (2015) reported two bilateral regions that are biased for visual attention, superior precentral sulcus (sPCS) and inferior precentral sulcus (iPCS), interleaved with two bilateral regions that are biased for auditory attention, transverse gyrus intersecting precentral sulcus (tgPCS) and caudal inferior frontal sulcus (cIFS). In the present study, we use fMRI to examine both the multiple-demand and sensory-bias hypotheses within caudal portions of human LFC (both men and women participated). Using visual and auditory 2-back tasks, we replicate the finding of two bilateral visual-biased and two bilateral auditory-biased LFC regions, corresponding to sPCS and iPCS and to tgPCS and cIFS, and demonstrate high within-subject reliability of these regions over time and across tasks. In addition, we assess MD responsiveness using BOLD signal recruitment and multi-task activation indices. In both, we find that the two visual-biased regions, sPCS and iPCS, exhibit stronger MD responsiveness than do the auditory-biased LFC regions, tgPCS and cIFS; however, neither reaches the degree of MD responsiveness exhibited by dorsal anterior cingulate/presupplemental motor area or by anterior insula. These results reconcile two competing views of LFC by demonstrating the coexistence of sensory specialization and MD functionality, especially in visual-biased LFC structures.SIGNIFICANCE STATEMENT Lateral frontal cortex (LFC) is known to play a number of critical roles in supporting human cognition; however, the functional organization of LFC remains controversial. The "multiple demand" (MD) hypothesis suggests that LFC regions provide domain-general support

  12. Preconditioning of Spatial and Auditory Cues: Roles of the Hippocampus, Frontal Cortex, and Cue-Directed Attention

    PubMed Central

    Talk, Andrew C.; Grasby, Katrina L.; Rawson, Tim; Ebejer, Jane L.

    2016-01-01

    Loss of function of the hippocampus or frontal cortex is associated with reduced performance on memory tasks, in which subjects are incidentally exposed to cues at specific places in the environment and are subsequently asked to recollect the location at which the cue was experienced. Here, we examined the roles of the rodent hippocampus and frontal cortex in cue-directed attention during encoding of memory for the location of a single incidentally experienced cue. During a spatial sensory preconditioning task, rats explored an elevated platform while an auditory cue was incidentally presented at one corner. The opposite corner acted as an unpaired control location. The rats demonstrated recollection of location by avoiding the paired corner after the auditory cue was in turn paired with shock. Damage to either the dorsal hippocampus or the frontal cortex impaired this memory ability. However, we also found that hippocampal lesions enhanced attention directed towards the cue during the encoding phase, while frontal cortical lesions reduced cue-directed attention. These results suggest that the deficit in spatial sensory preconditioning caused by frontal cortical damage may be mediated by inattention to the location of cues during the latent encoding phase, while deficits following hippocampal damage must be related to other mechanisms such as generation of neural plasticity. PMID:27999366

  13. 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

  14. 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.

  15. Ventral frontal cortex in children: morphology, social cognition and femininity/masculinity

    PubMed Central

    Murko, Vesna; Nopoulos, Peg

    2008-01-01

    The ventral frontal cortex (VFC) has been shown to differ morphologically between sexes. Social cognition, which many studies demonstrate involves the VFC, also differs between sexes, with females being more adept than males. In a previous study of subregions of the VFC in our lab, in an adult population, size of the straight gyrus (SG) but not the orbitofrontal cortex (OFC), differed between sexes and correlated with better performance on a test of social cognition and with greater identification with feminine characteristics. To investigate the relationship between VFC structure and social cognition in children, VFC gray matter volumes were measured on MRIs from 37 boys and 37 girls aged 7 to 17. The VFC was subdivided into the OFC and SG. Subjects were also administered a test of social perceptiveness and a rating scale of femininity/masculinity. In contrast to our findings in adults, the SG was slightly smaller in girls than boys. In girls, but not boys, smaller SG volumes significantly correlated with better social perception and higher identification with feminine traits. No volume differences by sex or significant correlations were found with the OFC. These data suggest a complex relationship between femininity, social cognition and SG morphology. PMID:19015107

  16. Predicting goals in action episodes attenuates BOLD response in inferior frontal and occipitotemporal cortex.

    PubMed

    Wurm, Moritz F; Hrkać, Mari; Morikawa, Yuka; Schubotz, Ricarda I

    2014-11-01

    Actions are usually made of several action steps gearing towards an overarching goal. During observation of such action episodes the overarching action goal becomes more and more clear and upcoming action steps can be predicted with increasing precision. To tap this process, the present fMRI study investigated the dynamic changes of neural activity during the observation of distinct action steps that cohere by an overarching goal. Our hypotheses specifically addressed the role of the inferior frontal gyrus (IFG), a region assumed to be a key hub for integration functions during action processing, as well as the role of regions involved in action perception (often referred to as action observation network or AON) that should benefit from the predictability of forthcoming action steps. Participants watched separate action steps that formed a coherent action goal or not (factor goal coherence) and were performed by a single actor or not (factor actor coherence). Independent of actor coherence, neural activity in IFG and occipitotemporal cortex decreased as a function of goal predictability during the unfolding of goal-coherent episodes. In addition, we identified a network (precuneus, dorsolateral prefrontal and orbitofrontal cortex, angular gyrus, and middle temporal gyrus) that showed increased activity for goal coherence. We conclude that IFG fosters the integration of action steps to build overarching goals. Identifying the unifying goal of an action episode allows anticipation, and thus efficient processing, of forthcoming action steps. To this end, past action steps of the action episode are buffered and recollected with recourse to episodic memory.

  17. Transcranial direct current stimulation of superior medial frontal cortex disrupts response selection during proactive response inhibition.

    PubMed

    Bender, Angela D; Filmer, Hannah L; Dux, Paul E

    2016-10-24

    Cognitive control is a vital executive process that is involved in selecting, generating, and maintaining appropriate, goal-directed behaviour. One operation that draws heavily on this resource is the mapping of sensory information to appropriate motor responses (i.e., response selection). Recently, a transcranial direct current stimulation (tDCS) study demonstrated that the left posterior lateral prefrontal cortex (pLPFC) is casually involved in response selection and response selection training. Correlational brain imaging evidence has also implicated the superior medial frontal cortex (SMFC) in response selection, and there is causal evidence that this brain region is involved in the proactive modulation of response tendencies when occasional stopping is required (response inhibition). However, to date there is only limited causal evidence that implicates the SMFC in response selection. Here, we investigated the role of SMFC in response selection, response selection training (Experiment 1) and response selection when occasional response inhibition is anticipated (Experiments 2 and 3) by employing anodal, cathodal, and sham tDCS. Cathodal stimulation of the SMFC modulated response selection by increasing reaction times in the context of proactive response inhibition. Our results suggest a context dependent role of the SMFC in response selection and hint that task set can influence the interaction between the brain and behaviour.

  18. Chronometric electrical stimulation of right inferior frontal cortex increases motor braking.

    PubMed

    Wessel, Jan R; Conner, Christopher R; Aron, Adam R; Tandon, Nitin

    2013-12-11

    The right inferior frontal cortex (rIFC) is important for stopping responses. Recent research shows that it is also activated when response emission is slowed down when stopping is anticipated. This suggests that rIFC also functions as a goal-driven brake. Here, we investigated the causal role of rIFC in goal-driven braking by using computer-controlled, event-related (chronometric), direct electrical stimulation (DES). We compared the effects of rIFC stimulation on trials in which responses were made in the presence versus absence of a stopping-goal ("Maybe Stop" [MS] vs "No Stop" [NS]). We show that DES of rIFC slowed down responses (compared with control-site stimulation) and that rIFC stimulation induced more slowing when motor braking was required (MS) compared with when it was not (NS). Our results strongly support a causal role of a rIFC-based network in inhibitory motor control. Importantly, the results extend this causal role beyond externally driven stopping to goal-driven inhibitory control, which is a richer model of human self-control. These results also provide the first demonstration of double-blind chronometric DES of human prefrontal cortex, and suggest that--in the case of rIFC--this could lead to augmentation of motor braking.

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

    PubMed

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

    2016-03-30

    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.

  20. Social Function in Boys with Cleft Lip and Palate: Relationship to Ventral Frontal Cortex Morphology

    PubMed Central

    Boes, Aaron D.; Murko, Vesna; Wood, Jessica L.; Langbehn, Douglas R.; Canady, John; Richman, Lynn; Nopoulos, Peg

    2007-01-01

    Isolated clefts of the lip and/or palate (ICLP) are developmental craniofacial abnormalities that have consistently been linked to increased social inhibition or shyness. Two explanations have been proposed: 1) psychosocial factors related to differences in facial appearance may lead to low self-concept and subsequent shyness, or 2) abnormal development of brain structures involved in social function, such as the ventral frontal cortex (VFC), may underlie the difference. To investigate these two possibilities this study was designed to evaluate measures of social function in relation to measures of self-concept and VFC morphology. Subjects included 30 boys (age 7-12) with ICLP and a comparison group of 43 boys without cleft in the same age category. Social function and self-concept were assessed using questionnaires with standardized scoring filled out by subjects and one of their parents. The cortical volume and surface area of the VFC, composed of the orbitofrontal cortex (OFC) and straight gyrus (SG), were evaluated using structural magnetic resonance imaging. The ICLP subjects had significantly impaired social function relative to the comparison group. No difference in self-concept was identified. VFC morphology revealed significant differences between groups, particularly decreased volume and surface area in the left SG of the ICLP group. Moreover, abnormal VFC measures were correlated with social dysfunction but measures of self-concept were not. These results are consistent with the possibility that aberrant VFC development may partially underlie social dysfunction in boys with ICLP. PMID:17537526

  1. Decreased dopamine concentrations in the frontal cortex after ablative surgeries in patients exhibiting self-injurious behavior: a microdialysis study.

    PubMed

    Liu, Aijun; Li, Anmin; Zhang, Haitao; Zhang, Zhiwen

    2014-01-01

    The authors examined brain neurochemistry in four patients with mental retardation with self-injurious behaviors after ablative surgeries. The authors found that surgeries in the human limbic system can alter dopamine levels in the frontal cortex over a 36-hour period.

  2. Selective effects of buspirone and molindone on dopamine metabolism and function in the striatum and frontal cortex of the rat.

    PubMed

    McMillen, B A; McDonald, C C

    1983-03-01

    The hypothesis that the nerve endings of the dopamine projection of the frontal cortex lack autoreceptors for regulation of tyrosine hydroxylase was tested by using the preferential inhibitors of dopamine autoreceptors, molindole and buspirone. In contrast to haloperidol, which elevates dopamine metabolism in the striatum and frontal cortex, both molindone and buspirone elicited little change in dopamine metabolism in the frontal cortex at doses up to 3.0 mg/kg, which cause the same maximal response in the corpus striatum as does haloperidol. Thus, the lack of autoreceptors in the frontal cortex is of pharmacological importance. That preferential inhibition of striatal dopamine autoreceptors may reverse catalepsy by enhancing synthesis and release of dopamine was tested by first inducing catalepsy with different drugs and then administering molindone or buspirone. Only buspirone (1.0 mg/kg) reversed catalepsy. This effect does not require presynaptic dopamine as catalepsy was reversed by buspirone in the dopamine-depleted rat (with 2.0 mg/kg R04-1284) as well as after postsynaptic dopamine receptor blockade by haloperidol of cis-flupenthixol. Thus, the mechanism for the reversal of catalepsy appears to be located efferent from the dopamine neuron. Buspirone, a non-benzodiazepine anti-anxiety drug, may prove useful for treatment of extrapyramidal motor disorders of either iatrogenic or idiosyncratic origin.

  3. 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.

  4. [Comparisons among different methods of culturing neural stem cells isolated from human fetal cortex].

    PubMed

    Ren, Ping; Guan, Yun Qian; Zhang, Yu

    2007-02-01

    Neural stem cells (NSCs) are proved to be promising cell sources for gene therapy and cell therapy. To pursue optimal conditions for the isolation and culture of neural stem cells residing in human fetal cortex,the cortical tissue was dissociated mechanically and digested with various enzymes. Short-term trypsin digestion combined with pipette dissociation proved to be the suitable method of isolating human NSCs derived from the fetal cortex. Furthermore,DMEM/F12 medium was superior to the neurobasal medium in the aspect of clonal formation. In repeated dissociation experiments,it was found that accutase, instead of trypsin,endowed the NSCs with better growth and efficient neurosphere formation.

  5. 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.

  6. Repeated administration of imipramine modifies GABAergic transmission in rat frontal cortex.

    PubMed

    Wabno, Joanna; Hess, Grzegorz

    2013-05-01

    Alterations in the functions of brain gamma-aminobutyric acid (GABA) inhibitory system and a distortion in the balance between excitatory and inhibitory synaptic transmission have been hypothesized to be possible causes of mood disorders. Experimental evidence points to modifications of GABAergic transmission as a result of prolonged treatment with antidepressant drugs, however, the influence of the tricyclic antidepressant imipramine on inhibitory synaptic transmission in the rat cerebral cortex has not yet been investigated. Therefore, in the present study the effects of single and repeated administration of imipramine were evaluated ex vivo in slices of the rat frontal cortex using electrophysiological approach. In slices prepared 2 days after the last drug administration from animals receiving imipramine for 14 days (dose 10 mg/kg p.o., twice daily) the mean frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded from layer II/III pyramidal neurons was decreased, while the mean amplitude of sIPSCs was increased. These effects were absent in slices obtained from rats which received imipramine once. Application of N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN 082), a selective mGluR7 allosteric agonist, to the slice incubation medium resulted in a decrease in the mean frequency of sIPSCs in preparations obtained from repeated imipramine-treated animals, in contrast to slices originating from control rats where no AMN 082-induced effects were observed. Repeated imipramine treatment reduced protein density levels of the three tested GABAA receptor subunits: α 1, β 2 and γ 2. These data indicate that repeated treatment of normal rats with imipramine results in a modification of the release mechanism of GABA from presynaptic terminals and its modulation by mGluR7 receptors as well as in an alteration in GABAA receptor subunit protein levels in the rat cerebral cortex.

  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. 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

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

    PubMed

    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.

  10. Motor areas of the frontal cortex in patients with motor eloquent brain lesions.

    PubMed

    Bulubas, Lucia; Sabih, Jamil; Wohlschlaeger, Afra; Sollmann, Nico; Hauck, Theresa; Ille, Sebastian; Ringel, Florian; Meyer, Bernhard; Krieg, Sandro M

    2016-12-01

    OBJECTIVE Because of its huge clinical potential, the importance of premotor areas for motor function itself and plastic reshaping due to tumors or ischemic brain lesions has received increased attention. Thus, in this study the authors used navigated transcranial magnetic stimulation (nTMS) to investigate whether tumorous brain lesions induce a change in motor cortex localization in the human brain. METHODS Between 2010 and 2013, nTMS motor mapping was performed in a prospective cohort of 100 patients with brain tumors in or adjacent to the rolandic cortex. Spatial data analysis was performed by normalization of the individual motor maps and creation of overlays according to tumor location. Analysis of motor evoked potential (MEP) latencies was performed regarding mean overall latencies and potentially polysynaptic latencies, defined as latencies longer than 1 SD above the mean value. Hemispheric dominance, lesion location, and motor-function deficits were also considered. RESULTS Graphical analysis showed that motor areas were not restricted to the precentral gyrus. Instead, they spread widely in the anterior-posterior direction. An analysis of MEP latency showed that mean MEP latencies were shortest in the precentral gyrus and longest in the superior and middle frontal gyri. The percentage of latencies longer than 1 SD differed widely across gyri. The dominant hemisphere showed a greater number of longer latencies than the nondominant hemisphere (p < 0.0001). Moreover, tumor location-dependent changes in distribution of polysynaptic latencies were observed (p = 0.0002). Motor-function deficit did not show any statistically significant effect. CONCLUSIONS The distribution of primary and polysynaptic motor areas changes in patients with brain tumors and highly depends on tumor location. Thus, these data should be considered for resection planning.

  11. Medial frontal cortex activity and loss-related responses to errors.

    PubMed

    Taylor, Stephan F; Martis, Brian; Fitzgerald, Kate D; Welsh, Robert C; Abelson, James L; Liberzon, Israel; Himle, Joseph A; Gehring, William J

    2006-04-12

    Making an error elicits activity from brain regions that monitor performance, especially the medial frontal cortex (MFC). However, uncertainty exists about whether the posterior or anterior/rostral MFC processes errors and to what degree affective responses to errors are mediated in the MFC, specifically the rostral anterior cingulate cortex (rACC). To test the hypothesis that rACC mediates a type of affective response, we conceptualized affect in response to an error as a reaction to loss and amplified this response with a monetary penalty. While subjects performed a cognitive interference task during functional magnetic resonance imaging, hemodynamic activity in the rACC was significantly greater when subjects lost money as a result of an error compared with errors that did not lead to monetary loss. A significant interaction between the incentive conditions and error events demonstrated that the effect was not merely attributable to working harder to win (or not lose) money, although an effect of motivation was noted in the mid-MFC. Activation foci also occurred in similar regions of the posterior MFC for error and interference processing, which were not modulated by the incentive conditions. However, at the level of the individual subject, substantial functional variability occurred along the MFC during error processing, including foci in the rostral/anterior extent of the MFC not appearing in the group analysis. The findings support the hypothesis that the rostral extent of the MFC (rACC) processes loss-related responses to errors, and individual differences may account for some of the reported variation of error-related foci in the MFC.

  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. Semantic monitoring of words with emotional connotation during fMRI: contribution of anterior left frontal cortex.

    PubMed

    Crosson, Bruce; Cato, M Allison; Sadek, Joseph R; Gökçay, Didem; Bauer, Russell M; Fischler, Ira S; Maron, Leeza; Gopinath, Kaundinya; Auerbach, Edward J; Browd, Samuel R; Briggs, Richard W

    2002-07-01

    Previous studies showed that cortex in the anterior portions of the left frontal and temporal lobes participates in generating words with emotional connotations and processing pictures with emotional content. If these cortices process the semantic attribute of emotional connotation, they should be active whenever processing emotional connotation, without respect to modality of input or mode of output. Thus, we hypothesized that they would activate during monitoring of words with emotional connotations. Sixteen normal subjects performed semantic monitoring of words with emotional connotations, animal names, and implement names during fMRI. Cortex in the anterior left frontal lobe demonstrated significant activity for monitoring words with emotional connotations compared to monitoring tone sequences, animal names, or implement names. Together, the current and previous results implicate cortex in the anterior left frontal lobe in semantic processing of emotional connotation, consistent with connections of this cortex to paralimbic association areas. Current findings also indicate that neural substrates for processing emotional connotation are independent of substrates for processing the categories of living and nonliving things.

  14. Dorsolateral frontal cortex and peripheral muscarinic receptors participation in the discriminative stimulus properties of scopolamine in rats.

    PubMed

    Aguayo-DelCastillo, Alejandra; Vélazquez-Martínez, David N; Sánchez-Castillo, Hugo; Casasola, César

    2013-08-01

    Organisms are capable of making decisions based on their ability to discriminate between different stimuli. This principle is fundamental for the adaptation of organisms to their environment, by emitting appropriate behaviors based on a previously acquired discriminative process. The present study analyzed the participation of the peripheral nervous system, the M₁ muscarinic receptor subtype, as well as the contribution of the dorsolateral frontal cortex to discrimination process using scopolamine as discriminative stimulus. Male Wistar rats were trained to discriminate between scopolamine (1.0 mg/kg) and saline injections (i.p.) using a two-lever operant procedure. Once discrimination was acquired, generalization curves for scopolamine, methylscopolamine, pirenzepine, dorsolateral frontal cortex lesion and control conditions were obtained. Results showed that rats were able to discriminate and generalize its responses to different doses of scopolamine but not for methylscopolamine or pirenzepine, thus the data suggest that discriminative properties of scopolamine are processed in CNS and that the M₁ receptor does not participate in this process. Dorsolateral frontal cortex lesion did not produce any statistically significant difference in the generalization curve, which suggests that a system different from the dorsolateral prefrontal cortex may be responsible for the control of stimulus produced by scopolamine. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. 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

  16. Large-scale Meta-analysis Suggests Low Regional Modularity in Lateral Frontal Cortex.

    PubMed

    de la Vega, Alejandro; Yarkoni, Tal; Wager, Tor D; Banich, Marie T

    2017-09-11

    Extensive fMRI study of human lateral frontal cortex (LFC) has yet to yield a consensus mapping between discrete anatomy and psychological states, partly due to the difficulty of inferring mental states from brain activity. Despite this, there have been few large-scale efforts to map the full range of psychological states across the entirety of LFC. Here, we used a data-driven approach to generate a comprehensive functional-anatomical mapping of LFC from 11 406 neuroimaging studies. We identified putatively separable LFC regions on the basis of whole-brain co-activation, revealing 14 clusters organized into 3 whole-brain networks. Next, we generated functional preference profiles by using multivariate classification to identify the psychological states that best predicted activity within each cluster. We observed large functional differences between networks, suggesting brain networks support distinct modes of processing. Within each network, however, we observed relatively low functional specificity, suggesting discrete psychological states are not strongly localized to individual regions; instead, our results are consistent with the view that individual LFC regions work as part of distributed networks to give rise to flexible behavior. Collectively, our results provide a comprehensive synthesis of a diverse neuroimaging literature using relatively unbiased data-driven methods. Published by Oxford University Press 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  17. 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. Copyright © 2015 the authors 0270-6474/15/353598-09$15.00/0.

  18. Perinatal nicotine treatment induces transient increases in NACHO protein levels in the rat frontal cortex.

    PubMed

    Wichern, Franziska; Jensen, Majbrit M; Christensen, Ditte Z; Mikkelsen, Jens D; Gondré-Lewis, Marjorie C; Thomsen, Morten S

    2017-03-27

    The nicotinic acetylcholine receptor (nAChR) regulator chaperone (NACHO) was recently identified as an important regulator of nAChR maturation and surface expression. Here we show that NACHO levels decrease during early postnatal development in rats. This decrease occurs earlier and to a greater degree in the frontal cortex (FC) compared with the hippocampus (HIP). We further show that rats exposed to nicotine during pre- and postnatal development exhibit significantly higher NACHO levels in the FC at postnatal day (PND) 21, but not at PND60. Repeated exposure to nicotine selectively during early (PND8-14) or late (PND54-60) postnatal stages did not affect NACHO protein levels in the FC or HIP, neither did exposure to high doses of the selective α7 nAChR agonists SSR180711, A-582941, or PNU-282987. However, we found significantly increased NACHO protein levels in the FC of PND36 rats after a single exposure to a combination of nicotine and the type II α7 nAChR positive allosteric modulator (PAM) PNU-120596, but not the type I PAM AVL-3288. These findings suggest that exposure to nAChR agonism affects NACHO protein levels, and that this effect is more pronounced during pre- or early postnatal development. The effect of PNU-120596 further suggests that the increase in NACHO expression is caused by activation rather than desensitization of nAChRs. Copyright © 2017 IBRO. All rights reserved.

  19. Cognitive functioning after medial frontal lobe damage including the anterior cingulate cortex: a preliminary investigation.

    PubMed

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

    2006-03-01

    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 compared with age and education matched healthy controls. Both patients showed intact intellectual, memory, and language abilities. No clear-cut abnormalities were noted in visuoperceptual functions. Speed of information processing was mildly reduced only in Patient 2 (bilateral ACC lesion). The patients demonstrated weak or impaired performance only on selective executive function tests. Performance on anterior attention tasks was satisfactory. We tentatively suggest that our findings are inconsistent with anterior attention theories of ACC function based on neuroimaging findings. We propose that the data may imply that the ACC does not have a central role in cognition. We speculate that our findings may be compatible with the view that the ACC integrates cognitive processing with autonomic functioning to guide behaviour.

  20. 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

    2016-04-12

    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.

  1. High channel count single-unit recordings from nonhuman primate frontal cortex.

    PubMed

    Mitz, Andrew R; Bartolo, Ramon; Saunders, Richard C; Browning, Philip G; Talbot, Thomas; Averbeck, Bruno B

    2017-09-01

    Single unit recording in behaving nonhuman primates is widely used to study the primate central nervous system. However, certain questions cannot be addressed without recording large numbers of neurons simultaneously. Multiple 96-electrode probes can be implanted at one time, but certain problems must be overcome to make this approach practical. We describe a series of innovations and practical guidance for implanting and recording from 8 arrays of 96 electrodes (768 electrodes) in the frontal cortex of Macaca mulatta. The methods include an individualized 3D-printed connector mounting platform, sequencing of assembly and surgical steps to minimize surgery time, and interventions to protect electrical connections of the implant. The methodology is robust and was successful in our hands on the first attempt. On average, we were able to isolate hundreds (535.7 and 806.9 in two animals) of high quality units in each session during one month of recording. To the best of our knowledge, this technique at least doubles the number of Blackrock arrays that have been successfully implanted in single animals. Although each technological component was pre-existing at the time we developed these methods, their amalgamation to solve the problem of high channel count recording is novel. The implantation of large numbers of electrodes opens new research possibilities. Refinements could lead to even greater capacity. Published by Elsevier B.V.

  2. Patterns of Activity in the Human Frontal and Parietal Cortex Differentiate Large and Small Saccades

    PubMed Central

    Grosbras, Marie-Hélène

    2016-01-01

    A vast literature indicates that small and large saccades, respectively, subserve different perceptual and cognitive strategies and may rely on different programming modes. While it is well-established that in monkeys’ main oculomotor brain regions small and large eye movements are controlled by segregated neuronal populations, the representation of saccade amplitude in the human brain remains unclear. To address this question we used functional magnetic resonance imaging to scan participants while they performed saccades toward targets at either short (4°) or large (30°) eccentricity. A regional multivoxel pattern analysis reveals that patterns of activity in the frontal eye-field and parietal eye fields discriminate between the execution of large or small saccades. This was not the case in the supplementary eye-fields nor in the inferior precentral cortex. These findings provide the first evidence of a representation of saccadic eye movement size in the fronto-parietal occulomotor circuit. They shed light on the respective roles of the different cortical oculomotor regions with respect to space perception and exploration, as well as on the homology of eye movement control between human and non-human primates. PMID:27833536

  3. Classification of frontal cortex haemodynamic responses during cognitive tasks using wavelet transforms and machine learning algorithms.

    PubMed

    Abibullaev, Berdakh; An, Jinung

    2012-12-01

    Recent advances in neuroimaging demonstrate the potential of functional near-infrared spectroscopy (fNIRS) for use in brain-computer interfaces (BCIs). fNIRS uses light in the near-infrared range to measure brain surface haemoglobin concentrations and thus determine human neural activity. Our primary goal in this study is to analyse brain haemodynamic responses for application in a BCI. Specifically, we develop an efficient signal processing algorithm to extract important mental-task-relevant neural features and obtain the best possible classification performance. We recorded brain haemodynamic responses due to frontal cortex brain activity from nine subjects using a 19-channel fNIRS system. Our algorithm is based on continuous wavelet transforms (CWTs) for multi-scale decomposition and a soft thresholding algorithm for de-noising. We adopted three machine learning algorithms and compared their performance. Good performance can be achieved by using the de-noised wavelet coefficients as input features for the classifier. Moreover, the classifier performance varied depending on the type of mother wavelet used for wavelet decomposition. Our quantitative results showed that CWTs can be used efficiently to extract important brain haemodynamic features at multiple frequencies if an appropriate mother wavelet function is chosen. The best classification results were obtained by a specific combination of input feature type and classifier. Copyright © 2012 IPEM. Published by Elsevier Ltd. All rights reserved.

  4. Unilateral medial frontal cortex lesions cause a cognitive decision-making deficit in rats.

    PubMed

    Croxson, Paula L; Walton, Mark E; Boorman, Erie D; Rushworth, Matthew F S; Bannerman, David M

    2014-12-01

    The medial frontal cortex (MFC) is critical for cost-benefit decision-making. Generally, cognitive and reward-based behaviour in rodents is not thought to be lateralised within the brain. In this study, however, we demonstrate that rats with unilateral MFC lesions show a profound change in decision-making on an effort-based decision-making task. Furthermore, unilateral MFC lesions have a greater effect when the rat has to choose to put in more effort for a higher reward when it is on the contralateral side of space to the lesion. Importantly, this could not be explained by motor impairments as these animals did not show a turning bias in separate experiments. In contrast, rats with unilateral dopaminergic midbrain lesions did exhibit a motoric turning bias, but were unimpaired on the effort-based decision-making task. This rare example of a cognitive deficit caused by a unilateral cortical lesion in the rat brain indicates that the MFC may have a specialised and lateralised role in evaluating the costs and benefits of actions directed to specific spatial locations. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  5. Conditioned opioid withdrawal decreases nociceptin/orphanin FQ levels in the frontal cortex and olfactory tubercle.

    PubMed

    Walker, John R; Terenius, Lars; Koob, George F

    2002-08-01

    Clinical evidence suggests that individuals experiencing drug withdrawal can become conditioned to environmental situations, whereby previously neutral stimuli can produce symptoms of withdrawal. It is believed that this "conditioned withdrawal" can have motivational significance, but the neurobiological basis for conditioned withdrawal is unknown. The goal of this study was to determine adaptations in endogenous opioid systems that may be responsible for expression of conditioned withdrawal. Opioid-dependent rats trained to lever press for food were exposed to tone and scent cues in the presence of naloxone or saline. Naloxone but not saline predictably suppressed responding for food. One month later and in a post-dependent state, all rats again were exposed to the cues but not naloxone. The conditioned cues alone suppressed responding for food in the rats previously paired with naloxone, but no suppression was seen in rats previously paired with saline. Radioimmunoassay (RIA) analysis for nociceptin/orphanin FQ (nociceptin), met-enkephalin-Arg-Phe (MEAP), and dynorphin A (dyn A) was performed from dissections of various brain regions of the rats undergoing conditioned withdrawal. Significant reductions in nociceptin peptide levels were seen in the frontal cortex and olfactory tubercle of these rats. Unconditioned opioid withdrawal and unconditioned footshock stress produced different patterns of opioid peptide regulation in separate groups of rats. These results shed light on adaptations of endogenous opioid systems to conditioned cues, stress, and withdrawal, all factors that play a role in motivating drug intake.

  6. Theta and beta synchrony coordinate frontal eye fields and anterior cingulate cortex during sensorimotor mapping

    PubMed Central

    Babapoor-Farrokhran, Sahand; Vinck, Martin; Womelsdorf, Thilo; Everling, Stefan

    2017-01-01

    The frontal eye fields (FEFs) and the anterior cingulate cortex (ACC) are commonly coactivated for cognitive saccade tasks, but whether this joined activation indexes coordinated activity underlying successful guidance of sensorimotor mapping is unknown. Here we test whether ACC and FEF circuits coordinate through phase synchronization of local field potential and neural spiking activity in macaque monkeys performing memory-guided and pro- and anti-saccades. We find that FEF and ACC showed prominent synchronization at a 3–9 Hz theta and a 12–30 Hz beta frequency band during the delay and preparation periods with a strong Granger-causal influence from ACC to FEF. The strength of theta- and beta-band coherence between ACC and FEF but not variations in power predict correct task performance. Taken together, the results support a role of ACC in cognitive control of frontoparietal networks and suggest that narrow-band theta and to some extent beta rhythmic activity indexes the coordination of relevant information during periods of enhanced control demands. PMID:28169987

  7. 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.

  8. Challenging the supremacy of the frontal lobe: early views (1906-1909) of Christfried Jakob on the human cerebral cortex.

    PubMed

    Théodoridou, Zoë D; Triarhou, Lazaros C

    2012-01-01

    This article focuses on a series of six studies that address functional localization in the frontal lobe; they were published in Argentina between 1906 and 1909 by Christfried Jakob (1866-1956), one of the great thinkers in early 20th century neuropathology and neurophilosophy. At that time, the localization-holism controversy was at a peak, having been triggered by the historic Marie-Déjerine aphasiology debate. Jakob held the view that constitutive physiological elements of cognition are localized. Nonetheless, he cast doubt on phrenological approaches that considered the frontal lobe as 'superior' to the other cortical regions. Jakob studied the human frontal lobe from fetal life through senility, in normality and pathology, including tumors, injuries, softening, general paralysis and dementia. Based on those finds, he considered strict localization theories a dead-end. Taking a critical look at Flechsig's ideas on the parallel ontogenies of frontal association centers and intellect, Jakob argued that the frontal lobe does not carry any selective advantage over the remaining human cerebral lobes or even over the frontal lobe in non-human primates. Regarding lesion experiments in laboratory animals, he pointed to methodological caveats, such as insufficient recovery time, that may lead to disorientating conclusions, and rejected élite brain research, calling it superficial and inexact. Jakob was convinced that the verification of the anatomical connections of the frontal lobe would elucidate its functions. Thus, he viewed the frontal lobe as a central station receiving input via olfactory pathways and thalamic radiations, pertinent to muscular and cutaneous senses, and attributed a perceptive character to a brain region traditionally associated with productive functions. Modern neuroscience seems to support Jakob's rejection of distinguishable motor and sensory regions and to adopt a cautious stance concerning oversimplified localization views. Copyright

  9. Near-infrared measurements of hemodynamic and oxygenation changes on the frontal cortex during breath holding, hyperventilation, and natural sleep

    NASA Astrophysics Data System (ADS)

    Noponen, Tommi E.; Kotilahti, Kalle; Toppila, Jussi; Nissila, Ilkka T.; Salmi, Tapani; Kajava, Timo T.; Katila, Toivo E.

    2003-07-01

    We have developed a frequency-domain near-infrared device suitable for physiological studies in human. In this work, a four-channel configuration of the instrument is applied to monitor hemodynamic and oxygenation changes in the frontal cortex of volunteers during different ventilation tasks. We use four different source-receiver separations (2, 3, 4, and 5 cm) and three wavelengths (760, 808, and 830 nm) to test the sensitivity of these parameters to cardiovascular and metabolic changes. Low-frequency oscillations (~ 0.02 Hz) and variations in heart rate during different ventilation tasks are investigated as well. We also study physiological changes during natural sleep using the frequency-domain instrument simultaneously with a polysomnography system containing a pulse oximeter. Our results indicate that hemodynamic and oxygenation changes in the frontal cortex during natural sleep can be detected using near-infrared measurements.

  10. Prenatal choline supplementation increases NGF levels in the hippocampus and frontal cortex of young and adult rats.

    PubMed

    Sandstrom, Noah J; Loy, Rebekah; Williams, Christina L

    2002-08-23

    Female Sprague-Dawley rats received approximately 300 mg/kg per day of choline chloride through their drinking water on days 11 of pregnancy through birth and the level of nerve growth factor (NGF) in the hippocampus and frontal cortex of their male offspring was measured at 20 and 90 days of age. Prenatal choline supplementation caused significant increases in hippocampal NGF levels at 20 and 90 days of age, while levels of NGF in the frontal cortex were elevated in choline-supplemented rats at 20 days of age, but not 90 days of age. These results suggest that increases in NGF levels during development or adulthood may be one mechanism underlying improvements in spatial and temporal memory of adult rats exposed to elevated levels of choline chloride perinatally.

  11. [The neuronal activity of the frontal cortex in dogs during a shift in motor conditioned reflex programs].

    PubMed

    Kozlov, A P; Vartanian, G A

    1995-01-01

    Two groups of units with different discharge patterns were identified in dog's frontal cortex during reinforcement period of reversal conditioning. Activity of the first group of units was closely related to reinforcement presentation and was influenced by reward/nonreward history in trials preceding the current one. Units of the second group displayed tonic increase of firing which followed food ingestion and persisted for 4-10 s.

  12. Parvalbumin, somatostatin and cholecystokinin as chemical markers for specific GABAergic interneuron types in the rat frontal cortex.

    PubMed

    Kawaguchi, Yasuo; Kondo, Satoru

    2002-01-01

    It remains to be clarified how many classes of GABAergic nonpyramidal cells exist in the cortical circuit. We have divided GABA cells in the rat frontal cortex into 3 groups, based on their firing characteristics: fast-spiking (FS) cells, late-spiking (LS) cells, and non-FS cells. Expression of calcium-binding proteins and peptides could be shown in separate groups of GABA cells in layers II/III and V of the frontal cortex: (1) parvalbumin cells, (2) somatostatin cells, (3) calretinin and/or vasoactive intestinal polypeptide (VIP) cells [partially positive for cholecystokinin (CCK)] and (4) large CCK cells (almost negative for VIP/calretinin). Combining the physiological and chemical properties of morphologically diverse nonpyramidal cells allows division into several groups, including FS basket cells containing parvalbumin, non-FS somatostatin Martinotti cells with ascending axonal arbors, and non-FS large basket cells positive for CCK. These subtypes show characteristic spatial distributions of axon collaterals and the innervation tendency of postsynaptic elements. With synchronized activity induced by cortical excitatory or inhibitory circuits, firing patterns were also found to differ. Subtype-selective occurrence of electrical coupling, finding for potassium channel Kv3.1 proteins, and cholinergic and serotonergic modulation supports our tentative classification. To clarify the functional architecture in the frontal cortex, it is important to reveal the connectional characteristics of GABA cell subtypes and determine whether they are similar to those in other cortical regions.

  13. Abnormal structural connectivity between the basal ganglia, thalamus, and frontal cortex in patients with disorders of consciousness.

    PubMed

    Weng, Ling; Xie, Qiuyou; Zhao, Ling; Zhang, Ruibin; Ma, Qing; Wang, Junjing; Jiang, Wenjie; He, Yanbin; Chen, Yan; Li, Changhong; Ni, Xiaoxiao; Xu, Qin; Yu, Ronghao; Huang, Ruiwang

    2017-03-10

    Consciousness loss in patients with severe brain injuries is associated with reduced functional connectivity of the default mode network (DMN), fronto-parietal network, and thalamo-cortical network. However, it is still unclear if the brain white matter connectivity between the above mentioned networks is changed in patients with disorders of consciousness (DOC). In this study, we collected diffusion tensor imaging (DTI) data from 13 patients and 17 healthy controls, constructed whole-brain white matter (WM) structural networks with probabilistic tractography. Afterward, we estimated and compared topological properties, and revealed an altered structural organization in the patients. We found a disturbance in the normal balance between segregation and integration in brain structural networks and detected significantly decreased nodal centralities primarily in the basal ganglia and thalamus in the patients. A network-based statistical analysis detected a subnetwork with uniformly significantly decreased structural connections between the basal ganglia, thalamus, and frontal cortex in the patients. Further analysis indicated that along the WM fiber tracts linking the basal ganglia, thalamus, and frontal cortex, the fractional anisotropy was decreased and the radial diffusivity was increased in the patients compared to the controls. Finally, using the receiver operating characteristic method, we found that the structural connections within the NBS-derived component that showed differences between the groups demonstrated high sensitivity and specificity (>90%). Our results suggested that major consciousness deficits in DOC patients may be related to the altered WM connections between the basal ganglia, thalamus, and frontal cortex.

  14. Changes in gene expression in the frontal cortex of rats with pilocarpine-induced status epilepticus after sleep deprivation.

    PubMed

    Hirotsu, Camila; Matos, Gabriela; Tufik, Sergio; Andersen, Monica Levy

    2013-05-01

    Sleep and epilepsy present a bidirectional interaction. Sleep complaints are common in epilepsy, and sleep deprivation may provoke seizures. However, the mechanisms underlying this relationship are unknown. Thus, this study investigated the effects of paradoxical sleep deprivation (PSD24h) and total sleep deprivation (TSD6h) in the expression of genes related to reactive oxygen species and nitric oxide production in the frontal cortex of a rodent model of temporal lobe epilepsy (PILO). The data show that PILO rats had increased NOX-2 expression and decreased SOD expression, independent of sleep. Higher NOX-2 expression was observed only in PILO rats subjected to the control condition and TSD6h. Also, eNOS and DDAH1 were increased in the PILO group submitted to TSD6h. Moreover, CAT expression in the frontal cortex of PILO rats submitted to PSD24h was reduced compared to that of PILO rats that were not sleep-deprived. The molecular changes found in the frontal cortex of PILO rats following sleep deprivation suggest a mechanism via oxidative stress. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Microphthalmia-associated transcription factor ensures the elongation of axons and dendrites in the mouse frontal cortex.

    PubMed

    Ohba, Koji; Takeda, Kazuhisa; Furuse, Tamio; Suzuki, Tomohiro; Wakana, Shigeharu; Suzuki, Takashi; Yamamoto, Hiroaki; Shibahara, Shigeki

    2016-12-01

    Long interspersed element-1 (LINE-1) is a mammalian transposable element, and its genomic insertion could cause neurological disorders in humans. Incidentally, LINE-1 is present in intron 3 of the microphthalmia-associated transcription factor (Mitf) gene of the black-eyed white mouse (Mitf(mi-bw) allele). Mice homozygous for the Mitf(mi-bw) allele show the white coat color with black eye and deafness. Here, we explored the functional consequences of the LINE-1 insertion in the Mitf gene using homozygous Mitf(mi-bw) mice on the C3H background (C3H-bw mice) or on the C57BL/6 background (bw mice). The open-field test showed that C3H-bw mice moved more irregularly in an unfamiliar environment during the 20-min period, compared to wild-type mice, suggesting the altered emotionality. Moreover, C3H-bw mice showed the lower serum creatinine levels, which may reflect the creatine deficiency. In fact, morphologically abnormal neurons and astrocytes were detected in the frontal cortex of bw mice. The immunohistochemical analysis of bw mouse tissues showed the lower intensity for expression of guanidinoacetate methyltransferase, a key enzyme in creatine synthesis, in neurons of the frontal cortex and in glomeruli and renal tubules. Thus, Mitf may ensure the elongation of axons and dendrites by maintaining creatine synthesis in the frontal cortex. © 2016 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  16. 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

  17. α2-Adrenoceptor Functionality in Postmortem Frontal Cortex of Depressed Suicide Victims

    PubMed Central

    Valdizán, Elsa M.; Díez-Alarcia, Rebeca; González-Maeso, Javier; Pilar-Cuéllar, Fuencisla; García-Sevilla, Jesús A.; Meana, J. Javier; Pazos, Angel

    2013-01-01

    Background Alterations in brain density and signaling associated with monoamine receptors are believed to play a role in depressive disorders. This study evaluates the functional status of α2A-adrenoceptors in postmortem frontal cortex of depressed subjects. Methods G-protein activation and inhibition of adenylyl cyclase (AC) activity induced by the α2-adrenoceptor agonist UK14304 were measured in triplicate in samples from 15 suicide victims with an antemortem diagnosis of major depression and 15 matched control subjects. Results Basal [35S] guanosine γ thio-phosphate (GTPγS) binding and cyclic adenosine monophosphate accumulation did not differ between groups. In depressed victims, an increase in [35S] GTPγS binding potency (EC50 = .58 μmol/L vs. EC50 = 3.31 μmol/L; p < .01; depressed vs. control) and a significant reduction in the maximal inhibition of AC activity (Imax = 27 ± 4% vs. Imax = 47 ± 5%; p < .01) were observed after incubation with the α2-adrenoceptor agonist UK14304. No differences were found between antidepressant-free and antidepressant-treated subjects. A significant relationship between EC50 values for [35S] GTPγS and Imax values for AC assay was found (n = 30; r = −.43; p < .05). Conclusions The dual regulation of α2A-adrenoceptor signaling pathways raises the possibility that factors affecting the G-protein cycle and/or selective access of Gαi/o–protein to AC might be relevant to receptor abnormalities in depression, providing further support for the involvement of α2A-adrenoceptors in the pathogenesis of depression. PMID:20864091

  18. Left frontal cortex connectivity underlies cognitive reserve in prodromal Alzheimer disease.

    PubMed

    Franzmeier, Nicolai; Duering, Marco; Weiner, Michael; Dichgans, Martin; Ewers, Michael

    2017-03-14

    To test whether higher global functional connectivity of the left frontal cortex (LFC) in Alzheimer disease (AD) is associated with more years of education (a proxy of cognitive reserve [CR]) and mitigates the association between AD-related fluorodeoxyglucose (FDG)-PET hypometabolism and episodic memory. Forty-four amyloid-PET-positive patients with amnestic mild cognitive impairment (MCI-Aβ+) and 24 amyloid-PET-negative healthy controls (HC) were included. Voxel-based linear regression analyses were used to test the association between years of education and FDG-PET in MCI-Aβ+, controlled for episodic memory performance. Global LFC (gLFC) connectivity was computed through seed-based resting-state fMRI correlations between the LFC (seed) and each voxel in the gray matter. In linear regression analyses, education as a predictor of gLFC connectivity and the interaction of gLFC connectivity × FDG-PET hypometabolism on episodic memory were tested. FDG-PET metabolism in the precuneus was reduced in MCI-Aβ+ compared to HC (p = 0.028), with stronger reductions observed in MCI-Aβ+ with more years of education (p = 0.006). In MCI-Aβ+, higher gLFC connectivity was associated with more years of education (p = 0.021). At higher levels of gLFC connectivity, the association between precuneus FDG-PET hypometabolism and lower memory performance was attenuated (p = 0.027). Higher gLFC connectivity is a functional substrate of CR that helps to maintain episodic memory relatively well in the face of emerging FDG-PET hypometabolism in early-stage AD. © 2017 American Academy of Neurology.

  19. Ethanol modifies differently aspartyl- and glutamyl-aminopeptidase activities in mouse frontal cortex synaptosomes.

    PubMed

    Mayas, María Dolores; Ramírez-Expósito, María Jesús; García, María Jesús; Ramírez, Manuel; Martínez-Martos, José Manuel

    2002-01-15

    Aminopeptidase A activity (aspartyl aminopeptidase (AspAP) and glutamyl aminopeptidase (GluAP) exerts angiotensinase activity due to its relation to the metabolism of angiotensins in the regional brain renin-angiotensin system (RAS). This activity may also modify the free amino acid pool through the release of N-terminal acidic amino acids. Ethanol (EtOH) exerts profound effects on the brain, inducing important neurological damages. Our purpose is to study the influence of EtOH on AspAP and GluAP activities on basal and K(+)-stimulated conditions, at the synapse level. We used mouse frontal cortex synaptosomes and their incubation supernatant in a Ca(2+)-containing or Ca(2+)-free artificial cerebrospinal fluid. We evaluate the possible contribution of these enzymatic activities on brain blood pressure regulation through RAS and/or the free acidic amino acid pool. The results obtained are correlated with several parameters of oxidative stress, such as free radical generation, lipid peroxidation, and protein oxidation. Under basal conditions, in synaptosomes, EtOH inhibits AspAP and GluAP activities independently of Ca(2+). In the supernatant, however, EtOH differently modulates the two enzyme activities under the various concentrations. Under K(+)-stimulated conditions, EtOH inhibits the K(+)-stimulated increase on AspAP and GluAP differently depending on the presence or absence of Ca(2+) and the concentration of EtOH used. These results invalidate the idea that excess free acidic amino acids could be released by AspAP and GluAP to induce neurodegeneration. The changes in AspAP and GluAP activities as a consequence of EtOH administration and their role in the brain RAS are discussed.

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

    PubMed

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

    2015-01-05

    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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. 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

  2. α₂-Adrenoceptor functionality in postmortem frontal cortex of depressed suicide victims.

    PubMed

    Valdizán, Elsa M; Díez-Alarcia, Rebeca; González-Maeso, Javier; Pilar-Cuéllar, Fuencisla; García-Sevilla, Jesús A; Meana, J Javier; Pazos, Angel

    2010-11-01

    Alterations in brain density and signaling associated with monoamine receptors are believed to play a role in depressive disorders. This study evaluates the functional status of α₂(A)-adrenoceptors in postmortem frontal cortex of depressed subjects. G-protein activation and inhibition of adenylyl cyclase (AC) activity induced by the α₂-adrenoceptor agonist UK14304 were measured in triplicate in samples from 15 suicide victims with an antemortem diagnosis of major depression and 15 matched control subjects. Basal [³⁵S] guanosine γ thio-phosphate (GTPγS) binding and cyclic adenosine monophosphate accumulation did not differ between groups. In depressed victims, an increase in [³⁵S] GTPγS binding potency (EC₅₀ = .58 μmol/L vs. EC₅₀ = 3.31 μmol/L; p < .01; depressed vs. control) and a significant reduction in the maximal inhibition of AC activity (I(max) = 27 ± 4% vs. I(max) = 47 ± 5%; p < .01) were observed after incubation with the α(2)-adrenoceptor agonist UK14304. No differences were found between antidepressant-free and antidepressant-treated subjects. A significant relationship between EC₅₀ values for [³⁵S] GTPγS and I(max) values for AC assay was found (n = 30; r = -.43; p < .05). The dual regulation of α(2A)-adrenoceptor signaling pathways raises the possibility that factors affecting the G-protein cycle and/or selective access of Gα(i/o)-protein to AC might be relevant to receptor abnormalities in depression, providing further support for the involvement of α₂(A)-adrenoceptors in the pathogenesis of depression. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. 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

  4. Acute treatment with doxorubicin affects glutamate neurotransmission in the mouse frontal cortex and hippocampus.

    PubMed

    Thomas, Theresa Currier; Beitchman, Joshua A; Pomerleau, Francois; Noel, Teresa; Jungsuwadee, Paiboon; Allan Butterfield, D; Clair, Daret K St; Vore, Mary; Gerhardt, Greg A

    2017-10-01

    Doxorubicin (DOX) is a potent chemotherapeutic agent known to cause acute and long-term cognitive impairments in cancer patients. Cognitive function is presumed to be primarily mediated by neuronal circuitry in the frontal cortex (FC) and hippocampus, where glutamate is the primary excitatory neurotransmitter. Mice treated with DOX (25mg/kg i.p.) were subjected to in vivo recordings under urethane anesthesia at 24h post-DOX injection or 5 consecutive days of cognitive testing (Morris Water Maze; MWM). Using novel glutamate-selective microelectrode arrays, amperometric recordings measured parameters of extracellular glutamate clearance and potassium-evoked release of glutamate within the medial FC and dentate gyrus (DG) of the hippocampus. By 24h post-DOX injection, glutamate uptake was 45% slower in the FC in comparison to saline-treated mice. In the DG, glutamate took 48% longer to clear than saline-treated mice. Glutamate overflow in the FC was similar between treatment groups, however, it was significantly increased in the DG of DOX treated mice. MWM data indicated that a single dose of DOX impaired swim speed without impacting total length traveled. These data indicate that systemic DOX treatment changes glutamate neurotransmission in key nuclei associated with cognitive function within 24h, without a lasting impact on spatial learning and memory. Understanding the functional effects of DOX on glutamate neurotransmission may help us understand and prevent some of the debilitating side effects of chemotherapeutic treatment in cancer survivors. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Betaine prevents homocysteine-induced memory impairment via matrix metalloproteinase-9 in the frontal cortex.

    PubMed

    Kunisawa, K; Nakashima, N; Nagao, M; Nomura, T; Kinoshita, S; Hiramatsu, M

    2015-10-01

    Betaine plays important roles that include acting as a methyl donor and converting homocysteine (Hcy) to methionine. Elevated plasma Hcy levels are known as hyperhomocysteinemia (HHcy) and contribute to impairments of learning and memory. Although it is commonly known that betaine plays an important role in Hcy metabolism, the effects of betaine on Hcy-induced memory impairment have not been investigated. Previously, we demonstrated the beneficial effects of betaine on acute stress and lipopolysaccharide-induced memory impairment. In the present study, we investigated whether betaine ameliorates Hcy-induced memory impairment and the underlying mechanisms of this putative effect. Mice were treated with Hcy (0.162mg/kg, s.c.) twice a day for nine days, and betaine (25mg/kg, s.c.) was administered 30min before the Hcy injections. The memory functions were evaluated using a spontaneous alternation performance test (Y-maze) at seven days and a step-down type passive avoidance test (SD) at nine and ten days after Hcy injection. We found that betaine suppressed the memory impairment induced by repeated Hcy injections. However, the blood concentrations of Hcy were significantly increased in the Hcy-treated mice immediately after the passive avoidance test, and betaine did not prevent this increase. Furthermore, Hcy induces redox stress in part by activating matrix metalloproteinase-9 (MMP-9), which leads to BBB dysfunction. Therefore, we tested whether betaine affected MMP-9 activity. Interestingly, treatment with betaine significantly inhibited Hcy-induced MMP-9 activity in the frontal cortex but not in the hippocampus after acute Hcy injection. These results suggest that the changes in MMP-9 activity after betaine treatment might have been partially responsible for the amelioration of the memory deficits and that MMP-9 might be a candidate therapeutic target for HHcy.

  6. Loss of Sleep Affects the Ultrastructure of Pyramidal Neurons in the Adolescent Mouse Frontal Cortex.

    PubMed

    de Vivo, Luisa; Nelson, Aaron B; Bellesi, Michele; Noguti, Juliana; Tononi, Giulio; Cirelli, Chiara

    2016-04-01

    The adolescent brain may be uniquely affected by acute sleep deprivation (ASD) and chronic sleep restriction (CSR), but direct evidence is lacking. We used electron microscopy to examine how ASD and CSR affect pyramidal neurons in the frontal cortex of adolescent mice, focusing on mitochondria, endosomes, and lysosomes that together perform most basic cellular functions, from nutrient intake to prevention of cellular stress. Adolescent (1-mo-old) mice slept (S) or were sleep deprived (ASD, with novel objects and running wheels) during the first 6-8 h of the light period, chronically sleep restricted (CSR) for > 4 days (using novel objects, running wheels, social interaction, forced locomotion, caffeinated water), or allowed to recover sleep (RS) for ∼32 h after CSR. Ultrastructural analysis of 350 pyramidal neurons was performed (S = 82; ASD = 86; CSR = 103; RS = 79; 4 to 5 mice/group). Several ultrastructural parameters differed in S versus ASD, S versus CSR, CSR versus RS, and S versus RS, although the different methods used to enforce wake may have contributed to some of the differences between short and long sleep loss. Differences included larger cytoplasmic area occupied by mitochondria in CSR versus S, and higher number of secondary lysosomes in CSR versus S and RS. We also found that sleep loss may unmask interindividual differences not obvious during baseline sleep. Moreover, using a combination of 11 ultrastructural parameters, we could predict in up to 80% of cases whether sleep or wake occurred at the single cell level. Ultrastructural analysis may be a powerful tool to identify which cellular organelles, and thus which cellular functions, are most affected by sleep and sleep loss. © 2016 Associated Professional Sleep Societies, LLC.

  7. Developmental Links between the Fetal and Adult Zones of the Adrenal Cortex Revealed by Lineage Tracing▿ †

    PubMed Central

    Zubair, Mohamad; Parker, Keith L.; Morohashi, Ken-ichirou

    2008-01-01

    The nuclear receptor Ad4BP/SF-1 is essential for development of the adrenal cortex and the gonads, which derive from a common adrenogonadal primordium. The adrenal cortex subsequently forms morphologically distinct compartments: the inner (fetal) and outer (definitive or adult) zones. Despite considerable effort, the mechanisms that mediate the differential development of the adrenal and gonadal primordia and the fetal and adult adrenal cortices remain incompletely understood. We previously identified a fetal adrenal-specific enhancer (FAdE) in the Ad4BP/SF-1 locus that directs transgene expression to the fetal adrenal cortex and demonstrated that this enhancer is autoregulated by Ad4BP/SF-1. We now combine the FAdE with the Cre/loxP system to trace cell lineages in which the FAdE was active at some stage in development. These lineage-tracing studies establish definitively that the adult cortex derives from precursor cells in the fetal cortex in which the FAdE was activated before the organization into two distinct zones. The potential of these fetal adrenocortical cells to enter the pathway that eventuates in cells of the adult cortex disappeared by embryonic day 14.5. Thus, these studies demonstrate a direct link between the fetal and adult cortices involving a transition that must occur before a specific stage of development. PMID:18809574

  8. 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

  9. Converging effects of diverse treatment modalities on frontal cortex in schizophrenia: A review of longitudinal functional magnetic resonance imaging studies.

    PubMed

    Kani, Ayse Sakalli; Shinn, Ann K; Lewandowski, Kathryn E; Öngür, Dost

    2017-01-01

    A variety of treatment options exist for schizophrenia, but the effects of these treatments on brain function are not clearly understood. To facilitate the development of more effective treatment strategies, it is important to identify how brain function in schizophrenia patients is affected by the diverse therapeutic approaches that are currently available. The aim of the present article is to systematically review the evidence for functional brain changes associated with different treatment modalities for schizophrenia. We searched PubMed for longitudinal functional MRI (fMRI) studies reporting on the effects of antipsychotic medications (APM), repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), cognitive remediation therapy (CRT) and cognitive behavioral therapy for psychosis (CBTp) on brain function in schizophrenia. Thirty six studies fulfilled the inclusion criteria. Functional alterations were observed in diverse brain regions. Across intervention modalities, changes in fMRI parameters were reported most commonly in frontal brain regions including prefrontal cortex, anterior cingulate and inferior frontal cortex. We conclude that current treatments for schizophrenia commonly induce functional brain alterations in frontal brain regions. However, interpretability is limited by inconsistency in task and region of interest selection, and failures to replicate. Further task independent fMRI studies examining treatment effects with whole brain analysis are needed to deepen our insights. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Absolute Theta Power in the Frontal Cortex During a Visuomotor Task: The Effect of Bromazepam on Attention.

    PubMed

    Gongora, Mariana; Peressuti, Caroline; Velasques, Bruna; Bittencourt, Juliana; Teixeira, Silmar; Arias-Carrión, Oscar; Cagy, Mauricio; Ribeiro, Pedro

    2015-10-01

    Bromazepam is a benzodiazepine, which has been widely employed in the treatment of anxiety. We investigated the electrophysiological changes in absolute theta power within the frontal cortex when individuals performed a visuomotor task under bromazepam. The sample of 17 healthy individuals was randomized into 2 experimental conditions, under which bromazepam 6 mg and placebo were administered on different days. All subjects were right -handed, with no mental or physical illness and were not using any psychoactive or psychotropic substance during the entire period of the study. We found an increase in reaction time under bromazepam compared with placebo . With regard to the electrophysiological variable, we found a lower theta power value in the prefrontal cortex prior to task execution, compared with after. We therefore suggested that this could be an increase of neural activity in this region, because of the subjects' readiness to perform the task, that is, because of their higher alertness. The right lateral frontal region showed lower theta power under bromazepam for pre- and post-finger movement. This could have occurred because of more effort to execute the task. In the left frontal region: premovement did not demonstrate any difference between conditions, possibly because the proposed task was simple to execute. In conclusion, theta power plays an important role in the analysis of visuomotor performance, assuming that bromazepam causes impairment on sustained attention and sensory perception. © EEG and Clinical Neuroscience Society (ECNS) 2014.

  11. Role of the Left Amygdala and Right Orbital Frontal Cortex in Emotional Interference Resolution Facilitation in Working Memory

    PubMed Central

    Levens, Sara M.; Devinsky, Orrin; Phelps, Elizabeth A.

    2011-01-01

    Previous research has shown that emotional information aids conflict resolution in working memory (Levens and Phelps, 2008). Using a Recency-probes working memory (WM) paradigm, Levens and Phelps found that positive and negative emotional stimuli reduced the amount of interference created when information that was once relevant conflicted with currently relevant information, suggesting that emotional information facilitates interference resolution in WM. To determine what regions of the prefrontal cortex (PFC) and temporal lobes are critical to the influence of emotional stimuli on interference resolution, we conducted a Recency-probes emotion paradigm with right and left unilateral frontal and temporal lobe lesion patients. The frontal lobe lesion patient group comprised individuals with unilateral ventral and dorsal PFC lesions. The temporal lobe lesion patient group comprised individuals with lesions of the amygdala and surrounding structures. Results indicate that when the left amygdala is damaged, emotional facilitation of interference resolution is absent (equal emotional and neutral interference levels), when the right orbital frontal cortex (OFC) is damaged, in contrast, emotional interference resolution is impaired (emotional interference levels are higher than neutral levels are). Based on these unique patterns we propose specific contributions for these regions in the emotional facilitation of interference resolution in WM. PMID:21835189

  12. 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.

  13. Distraction modulates connectivity of the cingulo-frontal cortex and the midbrain during pain--an fMRI analysis.

    PubMed

    Valet, Michael; Sprenger, Till; Boecker, Henning; Willoch, Frode; Rummeny, Ernst; Conrad, Bastian; Erhard, Peter; Tolle, Thomas R

    2004-06-01

    Neuroimaging studies with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have delineated a human pain network in vivo. Despite the recognition of cerebral structures engaged in pain transmission, the cerebral mechanisms involved in pain modulation are still not well understood. Here, we investigated healthy volunteers using fMRI during experimental heat pain and distraction induced by a visual incongruent color-word Stroop task. A factorial design permitted categorical and covariation analysis of four conditions, namely innocuous and noxious heat; with and without distraction. Pain without distraction evoked an activation pattern similar to that observed in previous neuroimaging pain studies. Distraction was associated with a significant reduction of the visual analogue scale (VAS) ratings for pain intensity and unpleasantness and a reduction of pain-related activation in multiple brain areas, particularly in the so-called 'medial pain system'. Distraction significantly increased the activation of the cingulo-frontal cortex including the orbitofrontal and perigenual anterior cingulate cortex (ACC), as well as the periaquaeductal gray (PAG) and the posterior thalamus. Covariation analysis revealed functional interaction between these structures during pain stimulation and distraction, but not during pain stimulation per se. According to our results, the cingulo-frontal cortex may exert top-down influences on the PAG and posterior thalamus to gate pain modulation during distraction.

  14. Feasibility Study: Comparison of Frontal Cortex Needle Core Versus Open Biopsy For Detection of Characteristic Proteinopathies of Neurodegenerative Diseases

    PubMed Central

    Serrano, Geidy E.; Intorcia, Anthony; Carew, Jeremiah; Chiarolanza, Glenn; Hidalgo, Jose A.; Sue, Lucia. I.; Dugger, Brittany N.; Saxon-LaBelle, Megan; Filon, Jessica; Scroggins, Alex; Pullen, Joel; Fornwalt, Brandon E.; Scott, Sarah; Sabbagh, Marwan M.; Adler, Charles H.; Akiyama, Haruhiko; Beach, Thomas G.

    2015-01-01

    The clinical diagnosis and classification of neurodegenerative diseases based on clinical examination or available biomarkers are currently insufficiently accurate. Although histological examination is considered the gold standard for diagnosis, brain biopsies have been avoided because of the high risk-benefit ratio. However, brain biopsies have previously been performed with a craniotomy and excision of approximately 1 cc of cerebral cortex tissue, and it is possible that needle core brain biopsies would have a lower morbidity and mortality risk. Here, we compared the ability of simulated needle core biopsy versus simulated open biopsy to detect the frontal cortex histopathology associated with common neurodegenerative diseases in the elderly using 144 autopsy-proven cases. Simulated needle core biopsy, as compared to simulated open biopsy, gave close to 90% sensitivity and specificity for identifying graded densities of β-amyloid and neuritic plaques, neurofibrillary tangles, phosphorylated α-synuclein, and phosphorylated TDP-43 pathology. This study shows that the presence and densities of the most common molecular pathologies may be histopathologically assessed in simulated frontal cortex needle biopsies with accuracy very close to that obtained by open cortical biopsy. An accurate estimation of the morbidity and mortality risk associated with cortical needle core biopsy will require specifically designed clinical trials in appropriate subjects. PMID:26230581

  15. The vestibular-related frontal cortex and its role in smooth-pursuit eye movements and vestibular-pursuit interactions

    PubMed Central

    Fukushima, Junko; Akao, Teppei; Kurkin, Sergei; Kaneko, Chris R.S.; Fukushima, Kikuro

    2006-01-01

    In order to see clearly when a target is moving slowly, primates with high acuity foveae use smooth-pursuit and vergence eye movements. The former rotates both eyes in the same direction to track target motion in frontal planes, while the latter rotates left and right eyes in opposite directions to track target motion in depth. Together, these two systems pursue targets precisely and maintain their images on the foveae of both eyes. During head movements, both systems must interact with the vestibular system to minimize slip of the retinal images. The primate frontal cortex contains two pursuit-related areas; the caudal part of the frontal eye fields (FEF) and supplementary eye fields (SEF). Evoked potential studies have demonstrated vestibular projections to both areas and pursuit neurons in both areas respond to vestibular stimulation. The majority of FEF pursuit neurons code parameters of pursuit such as pursuit and vergence eye velocity, gaze velocity, and retinal image motion for target velocity in frontal and depth planes. Moreover, vestibular inputs contribute to the predictive pursuit responses of FEF neurons. In contrast, the majority of SEF pursuit neurons do not code pursuit metrics and many SEF neurons are reported to be active in more complex tasks. These results suggest that FEF- and SEF-pursuit neurons are involved in different aspects of vestibular-pursuit interactions and that eye velocity coding of SEF pursuit neurons is specialized for the task condition. PMID:16917164

  16. [Histological and molecular study of fetal human adrenal cortex (12-36 wk)].

    PubMed

    Folligan, K; Bouvier, R; Targe, F; Morel, Y; Trouillas, J

    2005-12-01

    Histological and functional characteristics of the fetal human adrenals was studied in 119 normal fetuses aged 12 to 36 weeks development (WD). Immunocytochemical detection of steroidogenesis enzyme (3beta-HSD and P450 c21) and evaluation of cell proliferation using two nuclear markers (Ki-67 and PCNA) were performed in 70 of them. The human fetal adrenal cortex is composed of two morphologically distinct zones: the definitive peripheral zone and the fetal inner zone. From the 12th WD, we observed expression of an adherence protein (NCAM) and two steroidogenesis enzymes (3beta-HSD and P450 c21) in the definitive zone cells, attesting to the capacity of these cells to synthesize mineralocorticoids and/or cortisol. In the fetal zone, only P450 c21 immunoreactivity was detected. From the 14th WD, a transitional zone between the definitive zone and the fetal zone was identified by immunocytochemistry, with expression of 3b-HSD from the 21st WD. Only cells of the definitive zone proliferated from the 12th to 25th WD. The indexes of proliferation of PCNA and Ki-67, 40% and 25% respectively, decreased gradually and were lower than 1% at the 25th WD.

  17. 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…

  18. 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…

  19. Decoupling neural networks from reality: dissociative experiences in torture victims are reflected in abnormal brain waves in left frontal cortex.

    PubMed

    Ray, William J; Odenwald, Michael; Neuner, Frank; Schauer, Maggie; Ruf, Martina; Wienbruch, Christian; Rockstroh, Brigitte; Elbert, Thomas

    2006-10-01

    From a neuroscience perspective, little is known about the long-term effect of torture. Dissociative experiences and posttraumatic stress disorder are often the results of this experience. We examined psychological dissociation within a group of 23 torture victims and report its manifestations within neural networks in the human brain. In particular, we observed that dissociative experiences are associated with slow abnormal brain waves generated in left ventrolateral frontal cortex. Given that focal slow waves often result from depriving neural networks of major input, the present results may indicate decoupling of frontal affective processors from left cortical language areas. This interpretation is consistent with the fact that disturbed access to structured verbal memory concerning traumatic events is a core feature of the dissociative experience.

  20. Immunohistochemical localization of CB1 cannabinoid receptors in frontal cortex and related limbic areas in obese Zucker rats: effects of chronic fluoxetine treatment.

    PubMed

    Zarate, J; Churruca, I; Echevarría, E; Casis, L; López de Jesús, M; Saenz del Burgo, L; Sallés, J

    2008-10-21

    In the present study, we report on the application of two specific polyclonal antibodies to different intracellular domains of the CB1 cannabinoid receptor to define the expression of the neural CB1 cannabinoid receptor at the histochemical level in frontal cortex and related limbic areas of the obese Zucker rats. Higher levels of CB1 receptor expression in frontal, cingulated and piriform cortex, without differences in temporal, parietal and occipital cortex, were observed in obese Zucker rats, with respect to their lean littermates. CB1 phosphorylated receptor (CB1-P) levels were also higher in frontal, temporal, parietal and occipital cortex in obese rats with respect to lean controls. Potential involvement of brain cortical CB1 cannabinoid receptors in the long-term effects of fluoxetine was studied. Experimental animals were administered with fluoxetine (10 mg/kg, i.p.) daily for 3 weeks, whereas the control group was given 0.9% NaCl solution. In obese Zucker rats, a significant decrease in CB1 receptor levels, measured by western blot, was observed in brain cortex after fluoxetine treatment. Immunostaining for CB1 receptor expression was also carried out, showing a significant decrease in the density of neural cells positive for CB1 receptor in frontal, cingulate and piriform cortex, without changes in parietal, temporal and occipital regions. Regional prosencephalic immunostaining for CB1-P receptor level showed a significant decrease in the density of stained neural cells in frontal, temporal and parietal cortex, without changes in cingulated, piriform and occipital cortex. These results suggest the involvement of endocannabinoid system in the chronic effects of fluoxetine, especially in the frontal cortex.

  1. 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

  2. Ketamine suppresses hypoxia-induced inflammatory responses in the late-gestation ovine fetal kidney cortex.

    PubMed

    Chang, Eileen I; Zárate, Miguel A; Rabaglino, Maria B; Richards, Elaine M; Keller-Wood, Maureen; Wood, Charles E

    2016-03-01

    Acute fetal hypoxia is a form of fetal stress that stimulates renal vasoconstriction and ischaemia as a consequence of the physiological redistribution of combined ventricular output. Because of the potential ischaemia-reperfusion injury to the kidney, we hypothesized that it would respond to hypoxia with an increase in the expression of inflammatory genes, and that ketamine (an N-methyl-D-aspartate receptor antagonist) would reduce or block this response. Hypoxia was induced for 30 min in chronically catheterized fetal sheep (125 ± 3 days), with or without ketamine (3 mg kg(-1)) administered intravenously to the fetus 10 min prior to hypoxia. Gene expression in fetal kidney cortex collected 24 h after the onset of hypoxia was analysed using ovine Agilent 15.5k array and validated with qPCR and immunohistochemistry in four groups of ewes: normoxic control, normoxia + ketamine, hypoxic control and hypoxia + ketamine (n = 3-4 per group). Significant differences in gene expression between groups were determined with t-statistics using the limma package for R (P ≤ 0.05). Enriched biological processes for the 427 upregulated genes were immune and inflammatory responses and for the 946 downregulated genes were metabolic processes. Ketamine countered the effects of hypoxia on upregulated immune/inflammatory responses as well as the downregulated metabolic responses. We conclude that our transcriptomics modelling predicts that hypoxia activates inflammatory pathways and reduces metabolism in the fetal kidney cortex, and ketamine blocks or ameliorates this response. The results suggest that ketamine may have therapeutic potential for protection from ischaemic renal damage.

  3. Passive heat exposure induced by hot water leg immersion increased oxyhemoglobin in pre-frontal cortex to preserve oxygenation and did not contribute to impaired cognitive functioning.

    PubMed

    Wijayanto, Titis; Toramoto, Sayo; Tochihara, Yutaka

    2013-07-01

    This study investigated the effects of passive heat exposure on pre-frontal cortex oxygenation and cognitive functioning, specifically to examine whether the change in pre-frontal cortex oxygenation coincided with cognitive functioning during heat exposure. Eleven male students who participated in this study immersed their lower legs to the knees in three different water temperatures, 38 °C, 40 °C, and 42 °C water in an air temperature of 28 º C and 50 % relative humidity for 60 min. After 45 min of leg immersion they performed cognitive functioning tasks assessing their short-term memory while immersing their lower legs. There were higher rectal temperature (P < 0.05) and higher increase of oxyhemoglobin in both left (P < 0.05) and right (P < 0.05) pre-frontal cortex at the final stage of 45-min leg immersion in the 42 °C condition with unaltered tissue oxygenation index among the three conditions (P > 0.05). No statistical difference in cognitive functioning among the three conditions was observed with a higher increase of oxyhemoglobin during the cognitive functioning in the 42 °C condition for the left (P = 0.05) and right (P < 0.05) pre-frontal cortex. The findings of this study suggest, first, passive heat exposure increases oxygen delivery in the pre-frontal cortex to maintain pre-frontal cortex oxygenation; second, there is no evidence of passive heat exposure in cognitive functioning in this study; and third, the greater increases of oxyhemoglobin in the pre-frontal cortex during cognitive functioning at the hottest condition suggests a recruitment of available neural resources or greater effort to maintain the same performance at the same level as when they felt thermally comfortable.

  4. Passive heat exposure induced by hot water leg immersion increased oxyhemoglobin in pre-frontal cortex to preserve oxygenation and did not contribute to impaired cognitive functioning

    NASA Astrophysics Data System (ADS)

    Wijayanto, Titis; Toramoto, Sayo; Tochihara, Yutaka

    2013-07-01

    This study investigated the effects of passive heat exposure on pre-frontal cortex oxygenation and cognitive functioning, specifically to examine whether the change in pre-frontal cortex oxygenation coincided with cognitive functioning during heat exposure. Eleven male students who participated in this study immersed their lower legs to the knees in three different water temperatures, 38 °C, 40 °C, and 42 °C water in an air temperature of 28 º C and 50 % relative humidity for 60 min. After 45 min of leg immersion they performed cognitive functioning tasks assessing their short-term memory while immersing their lower legs. There were higher rectal temperature ( P < 0.05) and higher increase of oxyhemoglobin in both left ( P < 0.05) and right ( P < 0.05) pre-frontal cortex at the final stage of 45-min leg immersion in the 42 °C condition with unaltered tissue oxygenation index among the three conditions ( P > 0.05). No statistical difference in cognitive functioning among the three conditions was observed with a higher increase of oxyhemoglobin during the cognitive functioning in the 42 °C condition for the left ( P = 0.05) and right ( P < 0.05) pre-frontal cortex. The findings of this study suggest, first, passive heat exposure increases oxygen delivery in the pre-frontal cortex to maintain pre-frontal cortex oxygenation; second, there is no evidence of passive heat exposure in cognitive functioning in this study; and third, the greater increases of oxyhemoglobin in the pre-frontal cortex during cognitive functioning at the hottest condition suggests a recruitment of available neural resources or greater effort to maintain the same performance at the same level as when they felt thermally comfortable.

  5. Electrophysiological identification of mesencephalic ventromedial tegmental (VMT) neurons projecting to the frontal cortex, septum and nucleus accumbens.

    PubMed

    Deniau, J M; Thierry, A M; Feger, J

    1980-05-12

    The electrophysiological properties of neurons located in the mesencephalic ventromedial tegmentum (VMT) and the organization of the efferents of these neurons to the frontal cortex, the septum, the nucleus accumbens and the head of the striatum were studied in ketamine-anesthetized rats. The projections of the VMT cells were determined through use of the antidromic activation method. Our results show that VMT projections to different target areas originate mainly from different VMT neurons. However, in some cases single VMT neurons were found to send axon collaterals to two different areas. Three branching patterns were observed: septum-cortex, septum--nucleus accumbens and septum--striatum. The occasional observation of temporally distinct antodromic responses from a single area was considered to result from activation of different branches of the arborizing axon. The distribution of antidromic response latencies for VMT projections to each structure is discussed in relation to the question of dopaminergic versus non-dopaminergic mesolimbic and mesocortical systems.

  6. 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

    2016-09-06

    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.

  7. Trait aggression and trait impulsivity are not related to frontal cortex 5-HT2A receptor binding in healthy individuals.

    PubMed

    da Cunha-Bang, Sophie; Stenbæk, Dea Siggaard; Holst, Klaus; Licht, Cecilie Löe; Jensen, Peter Steen; Frokjaer, Vibe Gedsø; Mortensen, Erik Lykke; Knudsen, Gitte Moos

    2013-05-30

    Numerous studies indicate that the serotonergic (5-HT) transmitter system is involved in the regulation of impulsive aggression and there is from post-mortem, in vivo imaging and genetic studies evidence that the 5-HT2A receptor may be involved. We investigated 94 healthy individuals (60 men, mean age 47.0±18.7, range 23-86) to determine if trait aggression and trait impulsivity were related to frontal cortex 5-HT2A receptor binding (5-HT2AR) as measured with [18F]-altanserin PET imaging. Trait aggression and trait impulsivity were assessed with the Buss-Perry Aggression Questionnaire (AQ) and the Barratt Impulsiveness Scale 11 (BIS-11). Statistical analyses were conducted using a multiple linear regression model and internal consistency reliability of the AQ and BIS-11 was evaluated by Cronbach's alpha. Contrary to our hypothesis, results revealed no significant associations between 5-HT2AR and the AQ or BIS-11 total scores. Also, there was no significant interaction between gender and frontal cortex 5-HT2AR in predicting trait aggression and trait impulsivity. This is the first study to examine how 5-HT2AR relates to trait aggression and trait impulsivity in a large sample of healthy individuals. Our findings are not supportive of a selective role for 5-HT2AR in mediating the 5-HT related effects on aggression and impulsivity in psychiatrically healthy individuals. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  8. The galanin receptor agonist, galnon, attenuates cocaine-induced reinstatement and dopamine overflow in the frontal cortex.

    PubMed

    Ogbonmwan, Yvonne E; Sciolino, Natale R; Groves-Chapman, Jessica L; Freeman, Kimberly G; Schroeder, Jason P; Edwards, Gaylen L; Holmes, Philip V; Weinshenker, David

    2015-07-01

    Relapse represents one of the most significant problems in the long-term treatment of drug addiction. Cocaine blocks plasma membrane monoamine transporters and increases dopamine (DA) overflow in the brain, and DA is critical for the motivational and primary reinforcing effects of the drug as well as cocaine-primed reinstatement of cocaine seeking in rats, a model of relapse. Thus, modulators of the DA system may be effective for the treatment of cocaine dependence. The endogenous neuropeptide galanin inhibits DA transmission, and both galanin and the synthetic galanin receptor agonist, galnon, interfere with some rewarding properties of cocaine. The purpose of this study was to further assess the effects of galnon on cocaine-induced behaviors and neurochemistry in rats. We found that galnon attenuated cocaine-induced motor activity, reinstatement and DA overflow in the frontal cortex at a dose that did not reduce baseline motor activity, stable self-administration of cocaine, baseline extracellular DA levels or cocaine-induced DA overflow in the nucleus accumbens (NAc). Similar to cocaine, galnon had no effect on stable food self-administration but reduced food-primed reinstatement. These results indicate that galnon can diminish cocaine-induced hyperactivity and relapse-like behavior, possibly in part by modulating DA transmission in the frontal cortex. © 2014 Society for the Study of Addiction.

  9. Hyperactivity in the rat is associated with spontaneous low level of n-3 polyunsaturated fatty acids in the frontal cortex.

    PubMed

    Vancassel, S; Blondeau, C; Lallemand, S; Cador, M; Linard, A; Lavialle, M; Dellu-Hagedorn, F

    2007-06-18

    Inattention, hyperactivity and impulsiveness are the main symptoms of the heterogeneous attention-deficit/hyperactivity disorder (ADHD). It has been suggested that ADHD is associated with an imbalance in polyunsaturated fatty acid (PUFA) composition, with abnormal low levels of the main n-3 PUFA, DHA (22: 6n-3). DHA is highly accumulated in nervous tissue membranes and is implicated in neural function. Animal studies have shown that diet-induced lack of DHA in the brain leads to alterations in cognitive processes, but the relationship between DHA and hyperactivity is unclear. We examined the membrane phospholipid fatty acid profile in frontal cortex of rats characterized for attention, impulsiveness and motricity in various environmental contexts to determine the relationship between brain PUFA composition and the symptoms of ADHD. The amounts of n-3 PUFA in the PE were significantly correlated with nocturnal locomotor activity and the locomotor response to novelty: hyperactive individuals had less n-3 PUFA than hypoactive ones. We conclude that spontaneous hyperactivity in rats is the symptom of ADHD that best predicts the n-3 PUFA content of the frontal cortex. This differential model in rats should help to better understand the role of PUFA in several psychopathologies in which PUFA composition is modified.

  10. Severe alterations in lipid composition of frontal cortex lipid rafts from Parkinson's disease and incidental Parkinson's disease.

    PubMed

    Fabelo, Noemí; Martín, Virginia; Santpere, Gabriel; Marín, Raquel; Torrent, Laia; Ferrer, Isidre; Díaz, Mario

    2011-01-01

    Lipid rafts are cholesterol- and sphingomyelin-enriched microdomains that provide a highly saturated and viscous physicochemical microenvironment to promote protein-lipid and protein-protein interactions. We purified lipid rafts from human frontal cortex from normal, early motor stages of Parkinson's disease (PD) and incidental Parkinson's disease (iPD) subjects and analyzed their lipid composition. We observed that lipid rafts from PD and iPD cortices exhibit dramatic reductions in their contents of n-3 and n-6 long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (22:6-n3) and arachidonic acid (20:4n-6). Also, saturated fatty acids (16:0 and 18:0) were significantly higher than in control brains. Paralleling these findings, unsaturation and peroxidability indices were considerably reduced in PD and iPD lipid rafts. Lipid classes were also affected in PD and iPD lipid rafts. Thus, phosphatidylserine and phosphatidylinositol were increased in PD and iPD, whereas cerebrosides and sulfatides and plasmalogen levels were considerably diminished. Our data pinpoint a dramatic increase in lipid raft order due to the aberrant biochemical structure in PD and iPD and indicate that these abnormalities of lipid rafts in the frontal cortex occur at early stages of PD pathology. The findings correlate with abnormal lipid raft signaling and cognitive decline observed during the development of these neurodegenerative disorders.

  11. Expression of mRNA in the frontal cortex and hypothalamus in a rat model of acute carbon dioxide poisoning.

    PubMed

    Sato, Kazuo; Tsuji, Akiko; Usumoto, Yosuke; Kudo, Keiko; Yokoyama, Takeshi; Ikeda, Noriaki

    2016-03-01

    Acute carbon dioxide (CO2) poisoning causes no specific features that are revealed upon autopsy, and the pathophysiological mechanism of this syndrome is unclear. To address this issue, in the present study, we exposed rats to CO2 concentrations ranging from 10% to 60% and determined the effects on mRNA expression. According to the results of Gene Ontology (GO) and cluster analyses of microarrays data, we selected the following genes for further analysis: alkylglycerone phosphate synthase (Agps), hypocretin (Hcrt), tyrosine hydroxylase (Th), heat shock protein beta 2 (Hspb2), and opioid receptor delta 1 (Oprd1) expressed in the frontal cortex and renin (Ren), pancreatic polypeptide (Ppy), corticotropin releasing hormone receptor 2 (Crhr2), carbonic anhydrase 1 (Car1), and hypocretin receptor 1 (Hcrtr1) expressed in the hypothalamus. We found significant differences between the expression levels of Agps and Hspb2 mRNAs in the frontal cortex and that of Ppy, Crhr2 mRNAs in the hypothalamus in the presence of high concentrations of CO2. Further investigation of these genes may clarify the pathophysiology of acute CO2 poisoning and facilitate the development of novel forensic tests that can diagnose the cause of death. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. 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

  13. Chronic restraint stress promotes learning and memory impairment due to enhanced neuronal endoplasmic reticulum stress in the frontal cortex and hippocampus in male mice.

    PubMed

    Huang, Rong-Rong; Hu, Wen; Yin, Yan-Yan; Wang, Yu-Chan; Li, Wei-Ping; Li, Wei-Zu

    2015-02-01

    Chronic stress has been implicated in many types of neurodegenerative diseases, such as Alzheimer's disease (AD). In our previous study, we demonstrated that chronic restraint stress (CRS) induced reactive oxygen species (ROS) overproduction and oxidative damage in the frontal cortex and hippocampus in mice. In the present study, we investigated the effects of CRS (over a period of 8 weeks) on learning and memory impairment and endoplasmic reticulum (ER) stress in the frontal cortex and hippocampus in male mice. The Morris water maze was used to investigate the effects of CRS on learning and memory impairment. Immunohistochemistry and immunoblot analysis were also used to determine the expression levels of protein kinase C α (PKCα), 78 kDa glucose-regulated protein (GRP78), C/EBP-homologous protein (CHOP) and mesencephalic astrocyte-derived neurotrophic factor (MANF). The results revealed that CRS significantly accelerated learning and memory impairment, and induced neuronal damage in the frontal cortex and hippocampus CA1 region. Moreover, CRS significantly increased the expression of PKCα, CHOP and MANF, and decreased that of GRP78 in the frontal cortex and hippocampus. Our data suggest that exposure to CRS (for 8 weeks) significantly accelerates learning and memory impairment, and the mechanisms involved may be related to ER stress in the frontal cortex and hippocampus.

  14. Reciprocal activation/inactivation of ERK in the amygdala and frontal cortex is correlated with the degree of novelty of an open-field environment.

    PubMed

    Sanguedo, Frederico Velasco; Dias, Caio Vitor Bueno; Dias, Flavia Regina Cruz; Samuels, Richard Ian; Carey, Robert J; Carrera, Marinete Pinheiro

    2016-03-01

    Phosphorylated extracellular signal-regulated kinase (ERK) has been used to identify brain areas activated by exogenous stimuli including psychostimulant drugs. Assess the role of the amygdala in emotional responses. Experimental manipulations were performed in which environmental familiarity was the variable. To provide the maximal degree of familiarity, ERK was measured after removal from the home cage and re-placement back into the same cage. To maximize exposure to an unfamiliar environment, ERK was measured following placement into a novel open field. To assess whether familiarity was the critical variable in the ERK response to the novel open field, ERK was also measured after either four or eight placements into the same environment. ERK quantification was carried out in the amygdala, frontal cortex, and the nucleus accumbens. After home cage re-placement, ERK activation was found in the frontal cortex and nucleus accumbens but was absent in the amygdala. Following placement in a novel environment, ERK activation was more prominent in the amygdala than the frontal cortex or nucleus accumbens. In contrast, with habituation to the novel environment, ERK phosphors declined markedly in the amygdala but increased in the frontal cortex and nucleus accumbens to the level observed following home cage re-placement. The differential responsiveness of the amygdala versus the frontal cortex and the nucleus accumbens to a novel versus a habituated environment is consistent with a reciprocal interaction between these neural systems and points to their important role in the mediation of behavioral activation to novelty and behavioral inactivation with habituation.

  15. The toxic influence of dibromoacetic acid on the hippocampus and pre-frontal cortex of rat: involvement of neuroinflammation response and oxidative stress.

    PubMed

    Jiang, Wenbo; Li, Bai; Chen, Yingying; Gao, Shuying

    2017-08-26

    Dibromoacetic acid (DBA) exsits in drinking water as a by-product of disinfection as a result of chlorination or ozonation processes. Hippocampus and pre-frontal cortex are the key structures in memory formation and weanling babies are more sensitive to environmental toxicant than adults, so this study was conducted to evaluate the potential neurotoxicity effects of DBA exposure when administered intragastrically for 4 weeks to weanling Sprague-Dawley rats, at concentration of 0, 20, 50, 125 mg/kg via the neurobehavioral and neurochemical effects. Results indicated that animals weight gain and food consumption were not significantly affected by DBA. However, morris water maze test showed varying degrees of changes between control and high-dose group. Additionally, the level of malondialdehyde (MDA) and generation of reactive oxygen species (ROS) in the hippocampus and pre-frontal cortex of rats increased significantly. The activities of total superoxide dismutase (SOD) and the glutathione (GSH) content in the hippocampus and pre-frontal cortex of rats decreased significantly after treatment with DBA. Treatment with DBA increased the protein and mRNA expression of Iba-1, NF-κB, TNF-α, IL-6, IL-1β and HO-1 in the hippocampus and pre-frontal cortex of rats. These data suggested that DBA had a toxic influence on the hippocampus and pre-frontal cortex of rats, and that the mechanism of toxicity might be associated with the neuroinflammation response and oxidative stress.

  16. N-acetylaspartate levels of left frontal cortex are associated with verbal intelligence in women but not in men: a proton magnetic resonance spectroscopy study.

    PubMed

    Pfleiderer, B; Ohrmann, P; Suslow, T; Wolgast, M; Gerlach, A L; Heindel, W; Michael, N

    2004-01-01

    The left frontal cortex plays an important role in executive function and complex language processing inclusive of spoken language. The purpose of this work was to assess metabolite levels in the left and right prefrontal cortex and left anterior cingulum by proton magnetic resonance spectroscopy and relate results to verbal intelligence (Wechsler Adult Intelligence Scale revised) in a sample of college-educated healthy volunteers (dorsolateral prefrontal cortex [DLPFC]: n=52, 23 females, and left anterior cingulum: n=62, 22 females; age range: 20-75 years). In women only, N-acetylaspartate in the DLPFC and in the left anterior cingulate cortex was positively correlated with vocabulary scores. Our data support the hypothesis of existing gender differences regarding the involvement of the left frontal cortex in verbal processing as reflected in different correlations of specific metabolites with verbal scores.

  17. Development and Function of the Human Fetal Adrenal Cortex: A Key Component in the Feto-Placental Unit

    PubMed Central

    Ishimoto, Hitoshi

    2011-01-01

    Continuous efforts have been devoted to unraveling the biophysiology and development of the human fetal adrenal cortex, which is structurally and functionally unique from other species. It plays a pivotal role, mainly through steroidogenesis, in the regulation of intrauterine homeostasis and in fetal development and maturation. The steroidogenic activity is characterized by early transient cortisol biosynthesis, followed by its suppressed synthesis until late gestation, and extensive production of dehydroepiandrosterone and its sulfate, precursors of placental estrogen, during most of gestation. The gland rapidly grows through processes including cell proliferation and angiogenesis at the gland periphery, cellular migration, hypertrophy, and apoptosis. Recent studies employing modern technologies such as gene expression profiling and laser capture microdissection have revealed that development and/or function of the fetal adrenal cortex may be regulated by a panoply of molecules, including transcription factors, extracellular matrix components, locally produced growth factors, and placenta-derived CRH, in addition to the primary regulator, fetal pituitary ACTH. The role of the fetal adrenal cortex in human pregnancy and parturition appears highly complex, probably due to redundant and compensatory mechanisms regulating these events. Mounting evidence indicates that actions of hormones operating in the human feto-placental unit are likely mediated by mechanisms including target tissue responsiveness, local metabolism, and bioavailability, rather than changes only in circulating levels. Comprehensive study of such molecular mechanisms and the newly identified factors implicated in adrenal development should help crystallize our understanding of the development and physiology of the human fetal adrenal cortex. PMID:21051591

  18. Amygdala Contributions to Stimulus–Reward Encoding in the Macaque Medial and Orbital Frontal Cortex during Learning

    PubMed Central

    Averbeck, Bruno B.

    2017-01-01

    Orbitofrontal cortex (OFC), medial frontal cortex (MFC), and amygdala mediate stimulus–reward learning, but the mechanisms through which they interact are unclear. Here, we investigated how neurons in macaque OFC and MFC signaled rewards and the stimuli that predicted them during learning with and without amygdala input. Macaques performed a task that required them to evaluate two stimuli and then choose one to receive the reward associated with that option. Four main findings emerged. First, amygdala lesions slowed the acquisition and use of stimulus–reward associations. Further analyses indicated that this impairment was due, at least in part, to ineffective use of negative feedback to guide subsequent decisions. Second, the activity of neurons in OFC and MFC rapidly evolved to encode the amount of reward associated with each stimulus. Third, amygdalectomy reduced encoding of stimulus–reward associations during the evaluation of different stimuli. Reward encoding of anticipated and received reward after choices were made was not altered. Fourth, amygdala lesions led to an increase in the proportion of neurons in MFC, but not OFC, that encoded the instrumental response that monkeys made on each trial. These correlated changes in behavior and neural activity after amygdala lesions strongly suggest that the amygdala contributes to the ability to learn stimulus–reward associations rapidly by shaping encoding within OFC and MFC. SIGNIFICANCE STATEMENT Altered functional interactions among orbital frontal cortex (OFC), medial frontal cortex (MFC), and amygdala are thought to underlie several psychiatric conditions, many related to reward learning. Here, we investigated the causal contribution of the amygdala to the development of neuronal activity in macaque OFC and MFC related to rewards and the stimuli that predict them during learning. Without amygdala inputs, neurons in both OFC and MFC showed decreased encoding of stimulus–reward associations. MFC also

  19. Amygdala Contributions to Stimulus-Reward Encoding in the Macaque Medial and Orbital Frontal Cortex during Learning.

    PubMed

    Rudebeck, Peter H; Ripple, Joshua A; Mitz, Andrew R; Averbeck, Bruno B; Murray, Elisabeth A

    2017-02-22

    Orbitofrontal cortex (OFC), medial frontal cortex (MFC), and amygdala mediate stimulus-reward learning, but the mechanisms through which they interact are unclear. Here, we investigated how neurons in macaque OFC and MFC signaled rewards and the stimuli that predicted them during learning with and without amygdala input. Macaques performed a task that required them to evaluate two stimuli and then choose one to receive the reward associated with that option. Four main findings emerged. First, amygdala lesions slowed the acquisition and use of stimulus-reward associations. Further analyses indicated that this impairment was due, at least in part, to ineffective use of negative feedback to guide subsequent decisions. Second, the activity of neurons in OFC and MFC rapidly evolved to encode the amount of reward associated with each stimulus. Third, amygdalectomy reduced encoding of stimulus-reward associations during the evaluation of different stimuli. Reward encoding of anticipated and received reward after choices were made was not altered. Fourth, amygdala lesions led to an increase in the proportion of neurons in MFC, but not OFC, that encoded the instrumental response that monkeys made on each trial. These correlated changes in behavior and neural activity after amygdala lesions strongly suggest that the amygdala contributes to the ability to learn stimulus-reward associations rapidly by shaping encoding within OFC and MFC.SIGNIFICANCE STATEMENT Altered functional interactions among orbital frontal cortex (OFC), medial frontal cortex (MFC), and amygdala are thought to underlie several psychiatric conditions, many related to reward learning. Here, we investigated the causal contribution of the amygdala to the development of neuronal activity in macaque OFC and MFC related to rewards and the stimuli that predict them during learning. Without amygdala inputs, neurons in both OFC and MFC showed decreased encoding of stimulus-reward associations. MFC also showed

  20. Alteration of Rat Fetal Cerebral Cortex Development after Prenatal Exposure to Polychlorinated Biphenyls

    PubMed Central

    Naveau, Elise; Pinson, Anneline; Gérard, Arlette; Nguyen, Laurent; Charlier, Corinne; Thomé, Jean-Pierre; Zoeller, R. Thomas; Bourguignon, Jean-Pierre; Parent, Anne-Simone

    2014-01-01

    Polychlorinated biphenyls (PCBs) are environmental contaminants that persist in environment and human tissues. Perinatal exposure to these endocrine disruptors causes cognitive deficits and learning disabilities in children. These effects may involve their ability to interfere with thyroid hormone (TH) action. We tested the hypothesis that developmental exposure to PCBs can concomitantly alter TH levels and TH-regulated events during cerebral cortex development: progenitor proliferation, cell cycle exit and neuron migration. Pregnant rats exposed to the commercial PCB mixture Aroclor 1254 ended gestation with reduced total and free serum thyroxine levels. Exposure to Aroclor 1254 increased cell cycle exit of the neuronal progenitors and delayed radial neuronal migration in the fetal cortex. Progenitor cell proliferation, cell death and differentiation rate were not altered by prenatal exposure to PCBs. Given that PCBs remain ubiquitous, though diminishing, contaminants in human systems, it is important that we further understand their deleterious effects in the brain. PMID:24642964

  1. Alteration of rat fetal cerebral cortex development after prenatal exposure to polychlorinated biphenyls.

    PubMed

    Naveau, Elise; Pinson, Anneline; Gérard, Arlette; Nguyen, Laurent; Charlier, Corinne; Thomé, Jean-Pierre; Zoeller, R Thomas; Bourguignon, Jean-Pierre; Parent, Anne-Simone

    2014-01-01

    Polychlorinated biphenyls (PCBs) are environmental contaminants that persist in environment and human tissues. Perinatal exposure to these endocrine disruptors causes cognitive deficits and learning disabilities in children. These effects may involve their ability to interfere with thyroid hormone (TH) action. We tested the hypothesis that developmental exposure to PCBs can concomitantly alter TH levels and TH-regulated events during cerebral cortex development: progenitor proliferation, cell cycle exit and neuron migration. Pregnant rats exposed to the commercial PCB mixture Aroclor 1254 ended gestation with reduced total and free serum thyroxine levels. Exposure to Aroclor 1254 increased cell cycle exit of the neuronal progenitors and delayed radial neuronal migration in the fetal cortex. Progenitor cell proliferation, cell death and differentiation rate were not altered by prenatal exposure to PCBs. Given that PCBs remain ubiquitous, though diminishing, contaminants in human systems, it is important that we further understand their deleterious effects in the brain.

  2. 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…

  3. 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…

  4. 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…

  5. 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…

  6. Early growth hormone (GH) treatment promotes relevant motor functional improvement after severe frontal cortex lesion in adult rats.

    PubMed

    Heredia, Margarita; Fuente, A; Criado, J; Yajeya, J; Devesa, J; Riolobos, A S

    2013-06-15

    A number of studies, in animals and humans, describe the positive effects of the growth hormone (GH) treatment combined with rehabilitation on brain reparation after brain injury. We examined the effect of GH treatment and rehabilitation in adult rats with severe frontal motor cortex ablation. Thirty-five male rats were trained in the paw-reaching-for-food task and the preferred forelimb was recorded. Under anesthesia, the motor cortex contralateral to the preferred forelimb was aspirated or sham-operated. Animals were then treated with GH (0.15 mg/kg/day, s.c) or vehicle during 5 days, commencing immediately or 6 days post-lesion. Rehabilitation was applied at short- and long-term after GH treatment. Behavioral data were analized by ANOVA following Bonferroni post hoc test. After sacrifice, immunohistochemical detection of glial fibrillary acid protein (GFAP) and nestin were undertaken in the brain of all groups. Animal group treated with GH immediately after the lesion, but not any other group, showed a significant improvement of the motor impairment induced by the motor lesion, and their performances in the motor test were no different from sham-operated controls. GFAP immunolabeling and nestin immunoreactivity were observed in the perilesional area in all injured animals; nestin immunoreactivity was higher in GH-treated injured rats (mainly in animals GH-treated 6 days post-lesion). GFAP immunoreactivity was similar among injured rats. Interestingly, nestin re-expression was detected in the contralateral undamaged motor cortex only in GH-treated injured rats, being higher in animals GH-treated immediately after the lesion than in animals GH-treated 6 days post-lesion. Early GH treatment induces significant recovery of the motor impairment produced by frontal cortical ablation. GH effects include increased neurogenesis for reparation (perilesional area) and for increased brain plasticity (contralateral motor area). Copyright © 2013 Elsevier B.V. All rights

  7. Acute Stress Increases Depolarization-Evoked Glutamate Release in the Rat Prefrontal/Frontal Cortex: The Dampening Action of Antidepressants

    PubMed Central

    Farisello, Pasqualina; Zappettini, Simona; Tardito, Daniela; Barbiero, Valentina S.; Bonifacino, Tiziana; Mallei, Alessandra; Baldelli, Pietro; Racagni, Giorgio; Raiteri, Maurizio; Benfenati, Fabio; Bonanno, Giambattista; Popoli, Maurizio

    2010-01-01

    Background Behavioral stress is recognized as a main risk factor for neuropsychiatric diseases. Converging evidence suggested that acute stress is associated with increase of excitatory transmission in certain forebrain areas. Aim of this work was to investigate the mechanism whereby acute stress increases glutamate release, and if therapeutic drugs prevent the effect of stress on glutamate release. Methodology/Findings Rats were chronically treated with vehicle or drugs employed for therapy of mood/anxiety disorders (fluoxetine, desipramine, venlafaxine, agomelatine) and then subjected to unpredictable footshock stress. Acute stress induced marked increase in depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex in superfusion, and the chronic drug treatments prevented the increase of glutamate release. Stress induced rapid increase in the circulating levels of corticosterone in all rats (both vehicle- and drug-treated), and glutamate release increase was blocked by previous administration of selective antagonist of glucocorticoid receptor (RU 486). On the molecular level, stress induced accumulation of presynaptic SNARE complexes in synaptic membranes (both in vehicle- and drug-treated rats). Patch-clamp recordings of pyramidal neurons in the prefrontal cortex revealed that stress increased glutamatergic transmission through both pre- and postsynaptic mechanisms, and that antidepressants may normalize it by reducing release probability. Conclusions/Significance Acute footshock stress up-regulated depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex. Stress-induced increase of glutamate release was dependent on stimulation of glucocorticoid receptor by corticosterone. Because all drugs employed did not block either elevation of corticosterone or accumulation of SNARE complexes, the dampening action of the drugs on glutamate release must be downstream of these processes. This novel effect of

  8. Acute stress increases depolarization-evoked glutamate release in the rat prefrontal/frontal cortex: the dampening action of antidepressants.

    PubMed

    Musazzi, Laura; Milanese, Marco; Farisello, Pasqualina; Zappettini, Simona; Tardito, Daniela; Barbiero, Valentina S; Bonifacino, Tiziana; Mallei, Alessandra; Baldelli, Pietro; Racagni, Giorgio; Raiteri, Maurizio; Benfenati, Fabio; Bonanno, Giambattista; Popoli, Maurizio

    2010-01-05

    Behavioral stress is recognized as a main risk factor for neuropsychiatric diseases. Converging evidence suggested that acute stress is associated with increase of excitatory transmission in certain forebrain areas. Aim of this work was to investigate the mechanism whereby acute stress increases glutamate release, and if therapeutic drugs prevent the effect of stress on glutamate release. Rats were chronically treated with vehicle or drugs employed for therapy of mood/anxiety disorders (fluoxetine, desipramine, venlafaxine, agomelatine) and then subjected to unpredictable footshock stress. Acute stress induced marked increase in depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex in superfusion, and the chronic drug treatments prevented the increase of glutamate release. Stress induced rapid increase in the circulating levels of corticosterone in all rats (both vehicle- and drug-treated), and glutamate release increase was blocked by previous administration of selective antagonist of glucocorticoid receptor (RU 486). On the molecular level, stress induced accumulation of presynaptic SNARE complexes in synaptic membranes (both in vehicle- and drug-treated rats). Patch-clamp recordings of pyramidal neurons in the prefrontal cortex revealed that stress increased glutamatergic transmission through both pre- and postsynaptic mechanisms, and that antidepressants may normalize it by reducing release probability. Acute footshock stress up-regulated depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex. Stress-induced increase of glutamate release was dependent on stimulation of glucocorticoid receptor by corticosterone. Because all drugs employed did not block either elevation of corticosterone or accumulation of SNARE complexes, the dampening action of the drugs on glutamate release must be downstream of these processes. This novel effect of antidepressants on the response to stress, shown here for

  9. Connectivity-based parcellation of the macaque frontal cortex, and its relation with the cytoarchitectonic distribution described in current atlases.

    PubMed

    Cerliani, Leonardo; D'Arceuil, Helen; Thiebaut de Schotten, Michel

    2016-07-28

    Through its connectivity with the rest of the brain, a cortical region constrains its function. The advent of MRI methods such as diffusion-weighted imaging tractography allows us to estimate whole-brain anatomical connectivity at multiple seed regions in the same subject. This makes it possible to use data-driven techniques to define the spatial boundaries between adjacent brain regions characterized by sharply different connectivity. This approach has recently been employed to identify connectivity-based subdivisions of the human frontal lobe bearing an apparent similarity with cytoarchitectural subdivisions. However, the spatial relationships between the boundaries of cytoarchitectonic areas and tractography-based subdivisions remain largely hypothetical. In this work we present the first tractography-based parcellation of the frontal lobes in macaques. Diffusion-weighted data for tractography were acquired on ex vivo macaque brain specimens, ruling out the presence of various sources of noise present in acquisitions on living subjects. An unsupervised multivariate technique consistently showed the presence of 11 tractography-driven subdivisions in the frontal lobe across specimens. Comparison with several microstructural atlases suggested a heterogeneous relationship of these subdivisions with cytoarchitectonic areas: caudal frontal, medial and orbitofronal subdivisions featured the most consistent relationship between modalities, while lateral prefrontal subdivisions mostly differed from atlas-based cytoarchitectonic subdivisions. Other subdivisions were reminiscent of the organization of anatomical projections of the caudal motor cortex, as well as of the intrinsic orbitofrontal networks. Hence, although some cytoarchitectural and connectivity-based subdivisions share a similar spatial distribution, they should not necessarily be considered as equivalent. Instead, connectivity-based subdivisions appear to provide complementary information on the spatial

  10. Selective visual attention to emotional words: Early parallel frontal and visual activations followed by interactive effects in visual cortex.

    PubMed

    Schindler, Sebastian; Kissler, Johanna

    2016-10-01

    Human brains spontaneously differentiate between various emotional and neutral stimuli, including written words whose emotional quality is symbolic. In the electroencephalogram (EEG), emotional-neutral processing differences are typically reflected in the early posterior negativity (EPN, 200-300 ms) and the late positive potential (LPP, 400-700 ms). These components are also enlarged by task-driven visual attention, supporting the assumption that emotional content naturally drives attention. Still, the spatio-temporal dynamics of interactions between emotional stimulus content and task-driven attention remain to be specified. Here, we examine this issue in visual word processing. Participants attended to negative, neutral, or positive nouns while high-density EEG was recorded. Emotional content and top-down attention both amplified the EPN component in parallel. On the LPP, by contrast, emotion and attention interacted: Explicit attention to emotional words led to a substantially larger amplitude increase than did explicit attention to neutral words. Source analysis revealed early parallel effects of emotion and attention in bilateral visual cortex and a later interaction of both in right visual cortex. Distinct effects of attention were found in inferior, middle and superior frontal, paracentral, and parietal areas, as well as in the anterior cingulate cortex (ACC). Results specify separate and shared mechanisms of emotion and attention at distinct processing stages. Hum Brain Mapp 37:3575-3587, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Chronic Methamphetamine Induces Structural Changes in Frontal Cortex Neurons and Upregulates Type I Interferons

    PubMed Central

    Coutinho, Alice; Flynn, Claudia; Burdo, Tricia H.; Mervis, Ronald F.; Fox, Howard S.

    2008-01-01

    While methamphetamine-induced changes in brain neurotransmitters, their receptors and transporters are well studied; the means by which methamphetamine abuse results in cognitive and behavioral abnormalities is unknown. Here we administered methamphetamine chronically, in doses relevant to recreational usage patterns, to nonhuman primates. Neurostructural analysis revealed decreased dendritic material and loss of spines in frontal lobe neurons. Molecular examination demonstrated that type I interferons (interferon-alpha and -beta) increased in the frontal lobe in response to chronic methamphetamine treatment, in correlation with the neuronal changes. Chronic methamphetamine thus results in significant changes in the primate brain, inducing cytokines and altering neuronal structure, both of which can contribute to functional abnormalities. PMID:18594991

  12. Dissociable contributions of the orbitofrontal and infralimbic cortex to pavlovian autoshaping and discrimination reversal learning: further evidence for the functional heterogeneity of the rodent frontal cortex.

    PubMed

    Chudasama, Y; Robbins, Trevor W

    2003-09-24

    To examine possible heterogeneity of function within the ventral regions of the rodent frontal cortex, the present study compared the effects of excitotoxic lesions of the orbitofrontal cortex (OFC) and the infralimbic cortex (ILC) on pavlovian autoshaping and discrimination reversal learning. During the pavlovian autoshaping task, in which rats learn to approach a stimulus predictive of reward [conditional stimulus (CS+)], only the OFC group failed to acquire discriminated approach but was unimpaired when preoperatively trained. In the visual discrimination learning and reversal task, rats were initially required to discriminate a stimulus positively associated with reward. There was no effect of either OFC or ILC lesions on discrimination learning. When the stimulus-reward contingencies were reversed, both groups of animals committed more errors, but only the OFC-lesioned animals were unable to suppress the previously rewarded stimulus-reward association, committing more "stimulus perseverative" errors. In contrast, the ILC group showed a pattern of errors that was more attributable to "learning" than perseveration. These findings suggest two types of dissociation between the effects of OFC and ILC lesions: (1) OFC lesions impaired the learning processes implicated in pavlovian autoshaping but not instrumental simultaneous discrimination learning, whereas ILC lesions were unimpaired at autoshaping and their reversal learning deficit did not reflect perseveration, and (2) OFC lesions induced perseverative responding in reversal learning but did not disinhibit responses to pavlovian CS-. In contrast, the ILC lesion had no effect on response inhibitory control in either of these settings. The findings are discussed in the context of dissociable executive functions in ventral sectors of the rat prefrontal cortex.

  13. Left inferior frontal cortex and syntax: function, structure and behaviour in patients with left hemisphere damage

    PubMed Central

    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 hemisphere damage and healthy participants to ask whether the left inferior frontal gyrus is essential for syntactic processing. In a functional neuroimaging study, participants listened to spoken sentences that either contained a syntactically ambiguous or matched unambiguous phrase. Behavioural data on three tests of syntactic processing were subsequently collected. In controls, syntactic processing co-activated left hemisphere Brodmann areas 45/47 and posterior middle temporal gyrus. Activity in a left parietal cluster was sensitive to working memory demands in both patients and controls. Exploiting the variability in lesion location and performance in the patients, voxel-based correlational analyses showed that tissue integrity and neural activity—primarily in left Brodmann area 45 and posterior middle temporal gyrus—were correlated with preserved syntactic performance, but unlike the controls, patients were insensitive to syntactic preferences, reflecting their syntactic deficit. These results argue for the essential contribution of the left inferior frontal gyrus in syntactic analysis and highlight the functional relationship between left Brodmann area 45 and the left posterior middle temporal gyrus, suggesting that when this relationship breaks down, through damage to either region or to the connections between them, syntactic processing is impaired. On this view, the left inferior frontal gyrus may not itself be specialized for syntactic processing, but plays an essential role in the neural network that carries out syntactic computations. PMID:21278407

  14. Left inferior frontal cortex and syntax: function, structure and behaviour in patients with left hemisphere damage.

    PubMed

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

    2011-02-01

    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 hemisphere damage and healthy participants to ask whether the left inferior frontal gyrus is essential for syntactic processing. In a functional neuroimaging study, participants listened to spoken sentences that either contained a syntactically ambiguous or matched unambiguous phrase. Behavioural data on three tests of syntactic processing were subsequently collected. In controls, syntactic processing co-activated left hemisphere Brodmann areas 45/47 and posterior middle temporal gyrus. Activity in a left parietal cluster was sensitive to working memory demands in both patients and controls. Exploiting the variability in lesion location and performance in the patients, voxel-based correlational analyses showed that tissue integrity and neural activity-primarily in left Brodmann area 45 and posterior middle temporal gyrus-were correlated with preserved syntactic performance, but unlike the controls, patients were insensitive to syntactic preferences, reflecting their syntactic deficit. These results argue for the essential contribution of the left inferior frontal gyrus in syntactic analysis and highlight the functional relationship between left Brodmann area 45 and the left posterior middle temporal gyrus, suggesting that when this relationship breaks down, through damage to either region or to the connections between them, syntactic processing is impaired. On this view, the left inferior frontal gyrus may not itself be specialized for syntactic processing, but plays an essential role in the neural network that carries out syntactic computations.

  15. Differential coupling of visual cortex with default or frontal-parietal network based on goals.

    PubMed

    Chadick, James Z; Gazzaley, Adam

    2011-05-29

    The relationship between top-down enhancement and suppression of sensory cortical activity and large-scale neural networks remains unclear. Functional connectivity analysis of human functional magnetic resonance imaging data revealed that visual cortical areas that selectively process relevant information are functionally connected with the frontal-parietal network, whereas those that process irrelevant information are simultaneously coupled with the default network. This indicates that sensory cortical regions are differentially and dynamically coupled with distinct networks on the basis of task goals.

  16. The Involvement of Occipital and Inferior Frontal Cortex in the Phonological Learning of Chinese Characters

    PubMed Central

    Deng, Yuan; Chou, Tai-li; Ding, Guo-sheng; Peng, Dan-ling; Booth, James R.

    2016-01-01

    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 whole character’s pronunciation) with trained characters. Behavioral results showed that shared phonetic information improved performance for transfer characters. Neuroimaging results for trained characters over learning found increased activation in the right lingual gyrus, and greater activation enhancement in the left inferior frontal gyrus (Brodmann’s area 44) was correlated with higher accuracy improvement. Moreover, greater activation for transfer characters in these two regions at the late stage of training was correlated with better knowledge of the phonetic radical in a delayed recall test. The current study suggests that the right lingual gyrus and the left inferior frontal gyrus are crucial for the learning of Chinese characters and the generalization of that knowledge to novel characters. Left inferior frontal gyrus is likely involved in phonological segmentation, whereas right lingual gyrus may subserve processing visual–orthographic information. PMID:20807053

  17. The involvement of occipital and inferior frontal cortex in the phonological learning of Chinese characters.

    PubMed

    Deng, Yuan; Chou, Tai-li; Ding, Guo-sheng; Peng, Dan-ling; Booth, James R

    2011-08-01

    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 whole character's pronunciation) with trained characters. Behavioral results showed that shared phonetic information improved performance for transfer characters. Neuroimaging results for trained characters over learning found increased activation in the right lingual gyrus, and greater activation enhancement in the left inferior frontal gyrus (Brodmann's area 44) was correlated with higher accuracy improvement. Moreover, greater activation for transfer characters in these two regions at the late stage of training was correlated with better knowledge of the phonetic radical in a delayed recall test. The current study suggests that the right lingual gyrus and the left inferior frontal gyrus are crucial for the learning of Chinese characters and the generalization of that knowledge to novel characters. Left inferior frontal gyrus is likely involved in phonological segmentation, whereas right lingual gyrus may subserve processing visual-orthographic information.

  18. Effects of DBS in parkinsonian patients depend on the structural integrity of frontal cortex

    PubMed Central

    Muthuraman, Muthuraman; Deuschl, Günther; Koirala, Nabin; Riedel, Christian; Volkmann, Jens; Groppa, Sergiu

    2017-01-01

    While deep brain stimulation of the subthalamic nucleus (STN-DBS) has evolved to an evidence-based standard treatment for Parkinson’s disease (PD), the targeted cerebral networks are poorly described and no objective predictors for the postoperative clinical response exist. To elucidate the systemic mechanisms of DBS, we analysed cerebral grey matter properties using cortical thickness measurements and addressed the dependence of structural integrity on clinical outcome. Thirty one patients with idiopathic PD without dementia (23 males, age: 63.4 ± 9.3, Hoehn and Yahr: 3.5 ± 0.8) were selected for DBS treatment. The patients underwent whole-brain preoperative T1 MR-Imaging at 3 T. Grey matter integrity was assessed by cortical thickness measurements with FreeSurfer. The clinical motor outcome markedly improved after STN-DBS in comparison to the preoperative condition. The cortical thickness of the frontal lobe (paracentral area and superior frontal region) predicted the clinical improvement after STN-DBS. Moreover, in patients with cortical atrophy of these areas a higher stimulation voltage was needed for an optimal clinical response. Our data suggest that the effects of STN-DBS in PD directly depend on frontal lobe grey matter integrity. Cortical atrophy of this region might represent a distinct predictor of a poor motor outcome after STN-DBS in PD patients. PMID:28262813

  19. 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.

  20. MCT8 expression in human fetal cerebral cortex is reduced in severe intrauterine growth restriction.

    PubMed

    Chan, Shiao Y; Hancox, Laura A; Martín-Santos, Azucena; Loubière, Laurence S; Walter, Merlin N M; González, Ana-Maria; Cox, Phillip M; Logan, Ann; McCabe, Christopher J; Franklyn, Jayne A; Kilby, Mark D

    2014-02-01

    The importance of the thyroid hormone (TH) transporter, monocarboxylate transporter 8 (MCT8), to human neurodevelopment is highlighted by findings of severe global neurological impairment in subjects with MCT8 (SLC16A2) mutations. Intrauterine growth restriction (IUGR), usually due to uteroplacental failure, is associated with milder neurodevelopmental deficits, which have been partly attributed to dysregulated TH action in utero secondary to reduced circulating fetal TH concentrations and decreased cerebral thyroid hormone receptor expression. We postulate that altered MCT8 expression is implicated in this pathophysiology; therefore, in this study, we sought to quantify changes in cortical MCT8 expression with IUGR. First, MCT8 immunohistochemistry was performed on occipital and parietal cerebral cortex sections obtained from appropriately grown for gestational age (AGA) human fetuses between 19 weeks of gestation and term. Secondly, MCT8 immunostaining in the occipital cortex of stillborn IUGR human fetuses at 24-28 weeks of gestation was objectively compared with that in the occipital cortex of gestationally matched AGA fetuses. Fetuses demonstrated widespread MCT8 expression in neurons within the cortical plate and subplate, in the ventricular and subventricular zones, in the epithelium of the choroid plexus and ependyma, and in microvessel wall. When complicated by IUGR, fetuses showed a significant fivefold reduction in the percentage area of cortical plate immunostained for MCT8 compared with AGA fetuses (P<0.05), but there was no significant difference in the proportion of subplate microvessels immunostained. Cortical MCT8 expression was negatively correlated with the severity of IUGR indicated by the brain:liver weight ratios (r(2)=0.28; P<0.05) at post-mortem. Our results support the hypothesis that a reduction in MCT8 expression in the IUGR fetal brain could further compromise TH-dependent brain development.

  1. MCT8 expression in human fetal cerebral cortex is reduced in severe intrauterine growth restriction

    PubMed Central

    Chan, Shiao Y; Hancox, Laura A; Martín-Santos, Azucena; Loubière, Laurence S; Walter, Merlin N M; González, Ana-Maria; Cox, Phillip M; Logan, Ann; McCabe, Christopher J; Franklyn, Jayne A; Kilby, Mark D

    2014-01-01

    The importance of the thyroid hormone (TH) transporter, monocarboxylate transporter 8 (MCT8), to human neurodevelopment is highlighted by findings of severe global neurological impairment in subjects with MCT8 (SLC16A2) mutations. Intrauterine growth restriction (IUGR), usually due to uteroplacental failure, is associated with milder neurodevelopmental deficits, which have been partly attributed to dysregulated TH action in utero secondary to reduced circulating fetal TH concentrations and decreased cerebral thyroid hormone receptor expression. We postulate that altered MCT8 expression is implicated in this pathophysiology; therefore, in this study, we sought to quantify changes in cortical MCT8 expression with IUGR. First, MCT8 immunohistochemistry was performed on occipital and parietal cerebral cortex sections obtained from appropriately grown for gestational age (AGA) human fetuses between 19 weeks of gestation and term. Secondly, MCT8 immunostaining in the occipital cortex of stillborn IUGR human fetuses at 24–28 weeks of gestation was objectively compared with that in the occipital cortex of gestationally matched AGA fetuses. Fetuses demonstrated widespread MCT8 expression in neurons within the cortical plate and subplate, in the ventricular and subventricular zones, in the epithelium of the choroid plexus and ependyma, and in microvessel wall. When complicated by IUGR, fetuses showed a significant fivefold reduction in the percentage area of cortical plate immunostained for MCT8 compared with AGA fetuses (P<0.05), but there was no significant difference in the proportion of subplate microvessels immunostained. Cortical MCT8 expression was negatively correlated with the severity of IUGR indicated by the brain:liver weight ratios (r2=0.28; P<0.05) at post-mortem. Our results support the hypothesis that a reduction in MCT8 expression in the IUGR fetal brain could further compromise TH-dependent brain development. PMID:24204008

  2. 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

    2016-08-04

    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.

  3. 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

  4. NIRS-Based Hyperscanning Reveals Increased Interpersonal Coherence in Superior Frontal Cortex during Cooperation

    PubMed Central

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

    2011-01-01

    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

  5. Toll-like 4 receptor inhibitor TAK-242 decreases neuroinflammation in rat brain frontal cortex after stress

    PubMed Central

    2014-01-01

    Background The innate immune response is the first line of defence against invading microorganisms and it is also activated in different neurologic/neurodegenerative pathological scenarios. As a result, the family of the innate immune toll-like receptors (TLRs) and, in particular, the genetic/pharmacological manipulation of the TLR-4 signalling pathway emerges as a potential therapeutic strategy. Growing evidence relates stress exposure with altered immune responses, but the precise role of TLR-4 remains partly unknown. Methods The present study aimed to elucidate whether the elements of the TLR-4 signalling pathway are activated after acute stress exposure in rat brain frontal cortex and its role in the regulation of the stress-induced neuroinflammatory response, by means of its pharmacological modulation with the intravenous administration of the TLR-4 specific inhibitor TAK-242. Considering that TLR-4 responds predominantly to lipopolysaccharide from gram-negative bacteria, we checked whether increased intestinal permeability and a resultant bacterial translocation is a potential regulatory mechanism of stress-induced TLR-4 activation. Results Acute restraint stress exposure upregulates TLR-4 expression both at the mRNA and protein level. Stress-induced TLR-4 upregulation is prevented by the protocol of antibiotic intestinal decontamination made to reduce indigenous gastrointestinal microflora, suggesting a role for bacterial translocation on TLR-4 signalling pathway activation. TAK-242 pre-stress administration prevents the accumulation of potentially deleterious inflammatory and oxidative/nitrosative mediators in the brain frontal cortex of rats. Conclusions The use of TAK-242 or other TLR-4 signalling pathway inhibitory compounds could be considered as a potential therapeutic adjuvant strategy to constrain the inflammatory process taking place after stress exposure and in stress-related neuropsychiatric diseases. PMID:24410883

  6. The effect of risperidone on the mirtazapine-induced changes in extracellular monoamines in the rat frontal cortex.

    PubMed

    Kamińska, Katarzyna; Gołembiowska, Krystyna; Rogóż, Zofia

    2014-12-01

    The aim of our study was to understand the mechanism of clinical efficacy of the combination of an antidepressant and risperidone in drug-resistant depression. We studied the effect of an antidepressant (mirtazapine) and risperidone (atypical antipsychotic), given separately or jointly on extracellular levels of dopamine (DA), serotonin (5-HT) and noradrenaline (NA) in the rat frontal cortex. The animals were given a single intraperitoneal injection of risperidone (1mg/kg) and mirtazapine (10 and 20mg/kg). The release of monoamines in the rat frontal cortex was investigated using a microdialysis in freely moving animals, and monoamine levels were assayed by HPLC with coulochemical detection. Risperidone increased the cortical extracellular levels of DA, 5-HT and NA. Similarly, mirtazapine dose-dependently increased the cortical extracellular levels of the monoamines studied. A combination of mirtazapine either at the higher dose (20mg/kg) or at both doses (10 and 20mg/kg) with risperidone produced a significant effect on DA and NA release, respectively compared to the effect of any drug given alone. The increase in the DA (but not NA) release induced by mirtazapine plus risperidone was partly blocked by the selective 5-HT1A antagonist WAY 100635 (0.2mg/kg). Our data indicate that the increase of cortical extracellular levels of DA and NA by combined administration of mirtazapine and risperidone may be of crucial importance to the pharmacotherapy of drug resistant depression, and that, among other mechanisms, 5-HT1A, 5-HT2A, α2-adrenergic and histamine H1 receptors may play some role in this effect. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  7. Association between frontal cortex oxidative damage and beta-amyloid as a function of age in Down syndrome.

    PubMed

    Cenini, Giovanna; Dowling, Amy L S; Beckett, Tina L; Barone, Eugenio; Mancuso, Cesare; Murphy, Michael Paul; Levine, Harry; Lott, Ira T; Schmitt, Frederick A; Butterfield, D Allan; Head, Elizabeth

    2012-02-01

    Down syndrome (DS) is the most common genetic cause of intellectual disability in children, and the number of adults with DS reaching old age is increasing. By the age of 40 years, virtually all people with DS have sufficient neuropathology for a postmortem diagnosis of Alzheimer disease (AD). Trisomy 21 in DS leads to an overexpression of many proteins, of which at least two are involved in oxidative stress and AD: superoxide dismutase 1 (SOD1) and amyloid precursor protein (APP). In this study, we tested the hypothesis that DS brains with neuropathological hallmarks of AD have more oxidative and nitrosative stress than those with DS but without significant AD pathology, as compared with similarly aged-matched non-DS controls. The frontal cortex was examined in 70 autopsy cases (n=29 control and n=41 DS). By ELISA, we quantified soluble and insoluble Aβ40 and Aβ42, as well as oligomers. Oxidative and nitrosative stress levels (protein carbonyls, 4-hydroxy-2-trans-nonenal (HNE)-bound proteins, and 3-nitrotyrosine) were measured by slot-blot. We found that soluble and insoluble amyloid beta peptide (Aβ) and oligomers increase as a function of age in DS frontal cortex. Of the oxidative stress markers, HNE-bound proteins were increased overall in DS. Protein carbonyls were correlated with Aβ40 levels. These results suggest that oxidative damage, but not nitrosative stress, may contribute to the onset and progression of AD pathogenesis in DS. Conceivably, treatment with antioxidants may provide a point of intervention to slow pathological alterations in DS. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Quantitative analysis of basal dendritic tree of layer III pyramidal neurons in different areas of adult human frontal cortex.

    PubMed

    Zeba, Martina; Jovanov-Milosević, Natasa; Petanjek, Zdravko

    2008-01-01

    Large long projecting (cortico-cortical) layer IIIc pyramidal neurons were recently disclosed to be in the basis of cognitive processing in primates. Therefore, we quantitatively examined the basal dendritic morphology of these neurons by using rapid Golgi and Golgi Cox impregnation methods among three distinct Brodmann areas (BA) of an adult human frontal cortex: the primary motor BA4 and the associative magnopyramidal BA9 from left hemisphere and the Broca's speech BA45 from both hemispheres. There was no statistically significant difference in basal dendritic length or complexity, as dendritic spine number or their density between analyzed BA's. In addition, we analyzed each of these BA's immunocytochemically for distribution of SMI-32, a marker of largest long distance projecting neurons. Within layer IIIc, the highest density of SMI-32 immunopositive pyramidal neurons was observed in associative BA9, while in primary BA4 they were sparse. Taken together, these data suggest that an increase in the complexity of cortico-cortical network within human frontal areas of different functional order may be principally based on the increase in density of large, SMI-32 immunopositive layer IIIc neurons, rather than by further increase in complexity of their dendritic tree and synaptic network.

  9. Longitudinal Evidence for Increased Functional Response in Frontal Cortex for Older Adults with Hippocampal Atrophy and Memory Decline.

    PubMed

    Pudas, Sara; Josefsson, Maria; Rieckmann, Anna; Nyberg, Lars

    2017-01-23

    The functional organization of the frontal cortex is dynamic. Age-related increases in frontal functional responses have been shown during various cognitive tasks, but the cross-sectional nature of most past studies makes it unclear whether these increases reflect reorganization or stable individual differences. Here, we followed 130 older individuals' cognitive trajectories over 20-25 years with repeated neuropsychological assessments every 5th year, and identified individuals with stable or declining episodic memory. Both groups displayed significant gray matter atrophy over 2 successive magnetic resonance imaging sessions 4 years apart, but the decline group also had a smaller volume of the right hippocampus. Only individuals with declining memory demonstrated increased prefrontal functional responses during memory encoding and retrieval over the 4-year interval. Regions with increased functional recruitment were located outside, or on the borders of core task-related networks, indicating an expansion of these over time. These longitudinal findings offer novel insight into the mechanisms behind age-associated memory loss, and are consistent with a theoretical model in which hippocampus atrophy, past a critical threshold, induces episodic-memory decline and altered prefrontal functional organization. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Down syndrome: age-dependence of PiB binding in postmortem frontal cortex across the lifespan.

    PubMed

    LeVine, Harry; Spielmann, H Peter; Matveev, Sergey; Cauvi, Francesca Macchiavello; Murphy, M Paul; Beckett, Tina L; McCarty, Katie; Lott, Ira T; Doran, Eric; Schmitt, Frederick; Head, Elizabeth

    2017-03-14

    Beta-amyloid (Aβ) deposition in brain accumulates as a function of age in people with Down syndrome (DS) with subsequent development into Alzheimer disease neuropathology, typically by 40 years of age. In vivo imaging using the Pittsburgh compound B (PiB) ligand has facilitated studies linking Aβ, cognition, and dementia in DS. However, there are no studies of PiB binding across the lifespan in DS. The current study describes in vitro (3)H-PiB binding in the frontal cortex of autopsy cases with DS compared to non-DS controls. Tissue from 64 cases included controls (n = 25) and DS (n = 39). In DS, (3)H-PiB binding was significantly associated with age. After age 40 years in DS, (3)H-PiB binding rose dramatically along with increasing individual variability. (3)H-PiB binding correlated with the amount of Aβ42. Using fixed frontal tissue and fluorescent 6-CN-PiB, neuritic and cored plaques along with extensive cerebral amyloid angiopathy showed 6-CN-PiB binding. These results suggest that cortical PiB binding as shown by positron emission tomography imaging reflects plaques and cerebral amyloid angiopathy in DS brain.

  11. Immobility behavior during the forced swim test correlates with BNDF levels in the frontal cortex, but not with cognitive impairments.

    PubMed

    Borsoi, Milene; Antonio, Camila Boque; Viana, Alice Fialho; Nardin, Patrícia; Gonçalves, Carlos-Alberto; Rates, Stela Maris Kuze

    2015-03-01

    The forced swim test (FST) is widely used to evaluate the antidepressant-like activity of compounds and is sensitive to stimuli that cause depression-like behaviors in rodents. The immobility behavior observed during the test has been considered to represent behavioral despair. In addition, some studies suggest that the FST impairs rats' performance on cognitive tests, but these findings have rarely been explored. Thus, we investigated the effects of the FST on behavioral tests related to neuropsychiatric diseases that involve different cognitive components: novel object recognition (NOR), the object location test (OLT) and prepulse inhibition (PPI). Brain-derived neurotrophic factor (BDNF) levels in the frontal cortex and hippocampus were evaluated. The rats were forced to swim twice (15-min session followed by a 5-min session 24h later) and underwent cognitive tests 24h after the last swimming exposure. The FST impaired the rats' performance on the OLT and reduced the PPI and acoustic startle responses, whereas the NOR was not affected. The cognitive impairments were not correlated with an immobility behavior profile, but a significant negative correlation between the frontal BDNF levels and immobility behavior was identified. These findings suggest a protective role of BDNF against behavioral despair and demonstrate a deleterious effect of the FST on spatial memory and pre-attentive processes, which point to the FST as a tool to induce cognitive impairments analogous to those observed in depression and in other neuropsychiatric disorders.

  12. Prearcuate cortex in the Cebus monkey has cortical and subcortical connections like the macaque frontal eye field and projects to fastigial-recipient oculomotor-related brainstem nuclei.

    PubMed

    Leichnetz, G R; Gonzalo-Ruiz, A

    1996-01-01

    The cortical and subcortical connections of the prearcuate cortex were studied in capuchin monkeys (Cebus apella, albifrons) using the anterograde and retrograde transport capabilities of the horseradish peroxidase technique. The findings demonstrate remarkable similarities to those of the macaque frontal eye field and strongly support their homology. The report then focuses on specific prearcuate projections to oculomotor-related brainstem nuclei that were shown in a companion experiment to entertain connections with the caudal oculomotor portion of the cerebellar fastigial nucleus. The principal corticocortical connections of the cebus prearcuate cortex were with dorsomedial prefrontal cortex, lateral intraparietal sulcal cortex, posterior medial parietal cortex, and superior temporal sulcal cortex, which were for the most part reciprocal and columnar in organization. The connections of the dorsal prearcuate region were heavier to the dorsomedial prefrontal and posterior medial parietal cortices, and those of the ventral region were heavier to the superior temporal sulcal cortex. The prearcuate cortex projects to several brainstem areas which also receive projections from the caudal fastigial nucleus, including the supraoculomotor periaqueductal gray matter, superior colliculus, medial nucleus reticularis tegmenti pontis, dorsomedial basilar pontine nucleus, dorsolateral basilar pontine nucleus, nucleus reticularis pontis caudalis, pontine raphe, and nucleus prepositus hypoglossi. The findings define a neuroanatomical framework within which convergence of prearcuate (putative frontal eye field) and caudal fastigial nucleus connections might occur, facilitating their potential interaction in saccadic and smooth pursuit eye movement.

  13. Frontal cortex control dysfunction related to long-term suicide risk in recent-onset schizophrenia.

    PubMed

    Minzenberg, Michael J; Lesh, Tyler A; Niendam, Tara A; Yoon, Jong H; Rhoades, Remy N; Carter, Cameron S

    2014-08-01

    Suicide is highly-prevalent and the most serious outcome in schizophrenia, yet the disturbances in neural system functions that confer suicide risk remain obscure. Circuits operated by the prefrontal cortex (PFC) are altered in psychotic disorders, and various PFC changes are observed in post-mortem studies of completed suicide. We tested whether PFC activity during goal-representation (an important component of cognitive control) relates to long-term suicide risk in recent-onset schizophrenia. 35 patients with recent-onset of DSM-IV-TR-defined schizophrenia (SZ) were evaluated for long-term suicide risk (using the Columbia Suicide Severity Rating Scale) and functional MRI during cognitive control task performance. Group-level regression models associating control-related brain activation with suicide risk controlled for depression, psychosis and impulsivity. Within this group, past suicidal ideation was associated with lower activation with goal-representation demands in multiple PFC sectors. Among those with past suicidal ideation (n=18), reported suicidal behavior was associated with lower control-related activation in premotor cortex ipsilateral to the active primary motor cortex. This study provides unique evidence that suicide risk directly relates to PFC-based circuit dysfunction during goal-representation, in a major mental illness with significant suicide rates. Among those with suicidal ideation, the overt expression in suicidal behavior may stem from impairments in premotor cortex support of action-planning as an expression of control. Further work should address how PFC-based control function changes with risk over time, whether this brain-behavior relationship is specific to schizophrenia, and address its potential utility as a biomarker for interventions to mitigate suicide risk. Published by Elsevier B.V.

  14. 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.

  15. 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

  16. Accumulation of nuclear and mitochondrial DNA damage in the frontal cortex cells of patients with HIV-associated neurocognitive disorders.

    PubMed

    Zhang, Yulin; Wang, Meixia; Li, Hongjun; Zhang, Honghai; Shi, Ying; Wei, Feili; Liu, Daojie; Liu, Kai; Chen, Dexi

    2012-06-06

    Oxidative stress has been suggested to play a key role in the neuropathogenesis of HIV infection. HIV proteins (gp120, Tat) and proinflammatory cytokines can trigger the production of reactive oxygen species (ROS), resulting in DNA and RNA lesions. Among all the lesions induced by ROS, one of the most abundant lesions in DNA and RNA is 8-hydroxydeoxyguanosine (8-oxoG). Here, we studied accumulated DNA oxidative damage induced by ROS in the central nervous system (CNS) in tissue from neuro-AIDS patients. The frontal cortex of autopsy tissue from HIV-1 infected patients was adopted for analysis for HIV-1 subtype, nuclear and mitochondrial DNA lesions by immunofluorescence staining, qPCR and sequencing of PCR cloning. This study provides evidence that HIV infection in the CNS leads to nuclear and mitochondrial genomic DNA damage in the brain. High level of nuclear and mtDNA 8-oxoG damage were identified in the cortex autopsy tissue of HAND patients. Increased accumulation of mtDNA mutations and depletion occurs in brain tissue in a subset of HAND cases, and is significantly different from that observed in control cases. These findings suggest that higher level of ROS in the CNS of HAND patients would contribute to the HIV induced neuro-inflammation and apoptosis of neuronal and glial cells.

  17. Amyotrophic lateral sclerosis, gene deregulation in the anterior horn of the spinal cord and frontal cortex area 8: implications in frontotemporal lobar degeneration

    PubMed Central

    Andrés-Benito, Pol; Moreno, Jesús; Aso, Ester; Povedano, Mónica; Ferrer, Isidro

    2017-01-01

    Transcriptome arrays identifies 747 genes differentially expressed in the anterior horn of the spinal cord and 2,300 genes differentially expressed in frontal cortex area 8 in a single group of typical sALS cases without frontotemporal dementia compared with age-matched controls. Main up-regulated clusters in the anterior horn are related to inflammation and apoptosis; down-regulated clusters are linked to axoneme structures and protein synthesis. In contrast, up-regulated gene clusters in frontal cortex area 8 involve neurotransmission, synaptic proteins and vesicle trafficking, whereas main down-regulated genes cluster into oligodendrocyte function and myelin-related proteins. RT-qPCR validates the expression of 58 of 66 assessed genes from different clusters. The present results: a. reveal regional differences in de-regulated gene expression between the anterior horn of the spinal cord and frontal cortex area 8 in the same individuals suffering from sALS; b. validate and extend our knowledge about the complexity of the inflammatory response in the anterior horn of the spinal cord; and c. identify for the first time extensive gene up-regulation of neurotransmission and synaptic-related genes, together with significant down-regulation of oligodendrocyte- and myelin-related genes, as important contributors to the pathogenesis of frontal cortex alterations in the sALS/frontotemporal lobar degeneration spectrum complex at stages with no apparent cognitive impairment. PMID:28283675

  18. 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…

  19. 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…

  20. Transcriptional response of rat frontal cortex following acute In Vivo exposure to the pyrethroid insecticides permethrin and deltamethrin

    PubMed Central

    Harrill, Joshua A; Li, Zhen; Wright, Fred A; Radio, Nicholas M; Mundy, William R; Tornero-Velez, Rogelio; Crofton, Kevin M

    2008-01-01

    Background Pyrethroids are neurotoxic pesticides that interact with membrane bound ion channels in neurons and disrupt nerve function. The purpose of this study was to characterize and explore changes in gene expression that occur in the rat frontal cortex, an area of CNS affected by pyrethroids, following an acute low-dose exposure. Results Rats were acutely exposed to either deltamethrin (0.3 – 3 mg/kg) or permethrin (1 – 100 mg/kg) followed by collection of cortical tissue at 6 hours. The doses used range from those that cause minimal signs of intoxication at the behavioral level to doses well below apparent no effect levels in the whole animal. A statistical framework based on parallel linear (SAM) and isotonic regression (PIR) methods identified 95 and 53 probe sets as dose-responsive. The PIR analysis was most sensitive for detecting transcripts with changes in expression at the NOAEL dose. A sub-set of genes (Camk1g, Ddc, Gpd3, c-fos and Egr1) was then confirmed by qRT-PCR and examined in a time course study. Changes in mRNA levels were typically less than 3-fold in magnitude across all components of the study. The responses observed are consistent with pyrethroids producing increased neuronal excitation in the cortex following a low-dose in vivo exposure. In addition, Significance Analysis of Function and Expression (SAFE) identified significantly enriched gene categories common for both pyrethroids, including some relating to branching morphogenesis. Exposure of primary cortical cell cultures to both compounds resulted in an increase (~25%) in the number of neurite branch points, supporting the results of the SAFE analysis. Conclusion In the present study, pyrethroids induced changes in gene expression in the frontal cortex near the threshold for decreases in ambulatory motor activity in vivo. The penalized regression methods performed similarly in detecting dose-dependent changes in gene transcription. Finally, SAFE analysis of gene expression data

  1. 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.

  2. Inferior-frontal cortex phase synchronizes with the temporal-parietal junction prior to successful change detection.

    PubMed

    Micheli, Cristiano; Kaping, Daniel; Westendorff, Stephanie; Valiante, Taufik A; Womelsdorf, Thilo

    2015-10-01

    The inferior frontal gyrus (IFG) and the temporo-parietal junction (TPJ) are believed to be core structures of human brain networks that activate when sensory top-down expectancies guide goal directed behavior and attentive perception. But it is unclear how activity in IFG and TPJ coordinates during attention demanding tasks and whether functional interactions between both structures are related to successful attentional performance. Here, we tested these questions in electrocorticographic (ECoG) recordings in human subjects using a visual detection task that required sustained attentional expectancy in order to detect non-salient, near-threshold visual events. We found that during sustained attention the successful visual detection was predicted by increased phase synchronization of band-limited 15-30 Hz beta band activity that was absent prior to misses. Increased beta-band phase alignment during attentional engagement early during the task was restricted to inferior and lateral prefrontal cortex, but with sustained attention it extended to long-range IFG-TPJ phase synchronization and included superior prefrontal areas. In addition to beta, a widely distributed network of brain areas comprising the occipital cortex showed enhanced and reduced alpha band phase synchronization before correct detections. These findings identify long-range phase synchrony in the 15-30 Hz beta band as the mesoscale brain signal that predicts the successful deployment of attentional expectancy of sensory events. We speculate that localized beta coherent states in prefrontal cortex index 'top-down' sensory expectancy whose coupling with TPJ subregions facilitates the gating of relevant visual information.

  3. Liquid-Diet with Alcohol Alters Maternal, Fetal and Placental Weights and the Expression of Molecules Involved in Integrin Signaling in the Fetal Cerebral Cortex

    PubMed Central

    Rout, Ujjwal K.; Dhossche, Julie M.

    2010-01-01

    Maternal alcohol consumption during pregnancy causes wide range of behavioral and structural deficits in children, commonly known as Fetal Alcohol Syndrome (FAS). Children with FAS may suffer behavioral deficits in the absence of obvious malformations. In rodents, the exposure to alcohol during gestation changes brain structures and weights of offspring. The mechanism of FAS is not completely understood. In the present study, an established rat (Long-Evans) model of FAS was used. The litter size and the weights of mothers, fetuses and placentas were examined on gestation days 18 or 20. On gestation day 18, the effects of chronic alcohol on the expression levels of integrin receptor subunits, phospholipase-Cγ and N-cadherin were examined in the fetal cerebral cortices. Presence of alcohol in the liquid-diet reduced the consumption and decreased weights of mothers and fetuses but increased the placental weights. Expression levels of β1 and α3 integrin subunits and phospholipase-Cγ2 were significantly altered in the fetal cerebral cortices of mothers on alcohol containing diet. Results show that alcohol consumption during pregnancy even with protein, mineral and vitamin enriched diet may affect maternal and fetal health, and alter integrin receptor signaling pathways in the fetal cerebral cortex disturbing the development of fetal brains. PMID:21139874

  4. Liquid-diet with alcohol alters maternal, fetal and placental weights and the expression of molecules involved in integrin signaling in the fetal cerebral cortex.

    PubMed

    Rout, Ujjwal K; Dhossche, Julie M

    2010-11-01

    Maternal alcohol consumption during pregnancy causes wide range of behavioral and structural deficits in children, commonly known as Fetal Alcohol Syndrome (FAS). Children with FAS may suffer behavioral deficits in the absence of obvious malformations. In rodents, the exposure to alcohol during gestation changes brain structures and weights of offspring. The mechanism of FAS is not completely understood. In the present study, an established rat (Long-Evans) model of FAS was used. The litter size and the weights of mothers, fetuses and placentas were examined on gestation days 18 or 20. On gestation day 18, the effects of chronic alcohol on the expression levels of integrin receptor subunits, phospholipase-Cγ and N-cadherin were examined in the fetal cerebral cortices. Presence of alcohol in the liquid-diet reduced the consumption and decreased weights of mothers and fetuses but increased the placental weights. Expression levels of β(1) and α(3) integrin subunits and phospholipase-Cγ(2) were significantly altered in the fetal cerebral cortices of mothers on alcohol containing diet. Results show that alcohol consumption during pregnancy even with protein, mineral and vitamin enriched diet may affect maternal and fetal health, and alter integrin receptor signaling pathways in the fetal cerebral cortex disturbing the development of fetal brains.

  5. Orbito-frontal cortex and thalamus volumes in the patients with obsessive-compulsive disorder before and after cognitive behavioral therapy.

    PubMed

    Atmaca, Murad; Yildirim, Hanefi; Yilmaz, Seda; Caglar, Neslihan; Mermi, Osman; Korkmaz, Sevda; Akaslan, Unsal; Gurok, M Gurkan; Kekilli, Yasemin; Turkcapar, Hakan

    2016-01-05

    The effect of a variety of treatment modalities including psychopharmacological and cognitive behavioral therapy on the brain volumes and neurochemicals have not been investigated enough in the patients with obsessive-compulsive disorder. Therefore, in the present study, we aimed to investigate the effect of cognitive behavioral therapy on the volumes of the orbito-frontal cortex and thalamus regions which seem to be abnormal in the patients with obsessive-compulsive disorder. We hypothesized that there would be change in the volumes of the orbito-frontal cortex and thalamus. Twelve patients with obsessive-compulsive disorder and same number of healthy controls were included into the study. At the beginning of the study, the volumes of the orbito-frontal cortex and thalamus were compared by using magnetic resonance imaging. In addition, volumes of these regions were measured before and after the cognitive behavioral therapy treatment in the patient group. The patients with obsessive-compulsive disorder had greater left and right thalamus volumes and smaller left and right orbito-frontal cortex volumes compared to those of healthy control subjects at the beginning of the study. When we compared baseline volumes of the patients with posttreatment ones, we detected that thalamus volumes significantly decreased throughout the period for both sides and that the orbito-frontal cortex volumes significantly increased throughout the period for only left side. In summary, we found that cognitive behavioral therapy might volumetrically affect the key brain regions involved in the neuroanatomy of obsessive-compulsive disorder. However, future studies with larger sample are required. © The Author(s) 2016.

  6. Perirhinal cortex relays auditory information to the frontal motor cortices in the rat.

    PubMed

    Kyuhou, Shin-ichi; Matsuzaki, Ryuichi; Gemba, Hisae

    2003-12-26

    Auditory evoked potentials (AEPs) were recorded in the motor cortices (MC) with chronically implanted electrodes in the rat. Some of the AEPs in the MC, namely negative potentials on the surface and positive ones at a depth of 2 mm at latencies of about 50-150 ms, were abolished by limited bilateral lesions of the anterior perirhinal cortex (PERa) which was responsive to auditory stimulus, indicating that the AEPs in the MC were at least partially relayed in the PERa. The auditory response in the MC was prominently enhanced when water was supplied or the medial forebrain bundle was stimulated after auditory stimulus. These results indicate that the MC receives the reward associated auditory information from the PERa.

  7. 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.

  8. Oxidative stress in the progression of Alzheimer disease in the frontal cortex.

    PubMed

    Ansari, Mubeen A; Scheff, Stephen W

    2010-02-01

    We investigated oxidative stress in human postmortem frontal cortexfrom individuals characterized as mild cognitive impairment (n= 8), mild/moderate Alzheimer disease (n = 4), and late-stage Alzheimer disease (n = 9). Samples from subjects with no cognitive impairment (n = 10) that were age- and postmortem interval-matched with these cases were used as controls. The short postmortem intervalbrain samples were processed for postmitochondrial supernatant, nonsynaptic mitochondria, and synaptosome fractions. Samples were analyzed for several antioxidants (glutathione, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, glucose-6-phosphate dehydrogenase, superoxide dismutase, catalase) and the oxidative marker, thiobarbituric acid reactive substances. The tissue was also analyzed for possible changes in protein damage using neurochemical markers for protein carbonyls, 3-nitrotyrosine, 4-hydroxynonenal, andacrolein. All 3 neuropil fractions (postmitochondrial supernatant, mitochondrial, and synaptosomal) demonstrated significant disease-dependent increases in oxidative markers. The highest changes were observed in the synaptosomal fraction. Both mitochondrial and synaptosomal fractions had significant declines in antioxidants (glutathione, glutathione peroxidase, glutathione-S-transferase, and superoxide dismutase). Levels of oxidative markers significantly correlated with Mini-Mental Status Examination scores. Oxidative stress was more localized to the synapses, with levels increasing in a disease-dependent fashion. These correlations implicate an involvement of oxidative stress in Alzheimer disease-related synaptic loss.

  9. Cognitive control dysfunction and abnormal frontal cortex activation in stimulant drug users and their biological siblings

    PubMed Central

    Smith, D G; Jones, P S; Bullmore, E T; Robbins, T W; Ersche, K D

    2013-01-01

    Cognitive and neural abnormalities are known to accompany chronic drug abuse, with impairments in cognition and changes in cortical structure seen in stimulant-dependent individuals. However, premorbid differences have also been observed in the brains and behavior of individuals at risk for substance abuse, before they develop dependence. Endophenotype research has emerged as a useful method for assessing preclinical traits that may be risk factors for pathology by studying patient populations and their undiagnosed first-degree relatives. This study used the color-word Stroop task to assess executive functioning in stimulant-dependent individuals, their unaffected biological siblings and unrelated healthy control volunteers using a functional magnetic resonance imaging paradigm. Both the stimulant-dependent and sibling participants demonstrated impairments in cognitive control and processing speed on the task, registering significantly longer response latencies. However, the two groups generated very different neural responses, with the sibling participants exhibiting a significant decrease in activation in the inferior frontal gyrus compared with both stimulant-dependent individuals and control participants. Both target groups also demonstrated a decrease in hemispheric laterality throughout the task, exhibiting a disproportionate increase in right hemispheric activation, which was associated with their behavioral inefficiencies. These findings not only suggest a possible risk factor for stimulant abuse of poor inhibitory control and cortical inefficiency but they also demonstrate possible adaptations in the brains of stimulant users. PMID:23673468

  10. Reduced mitochondrial activity is early and steady in the entorhinal cortex but it is mainly unmodified in the frontal cortex in Alzheimer's disease.

    PubMed

    Armand-Ugon, Mercedes; Ansoleaga, Belen; Berjaoui, Sara; Ferrer, Isidro

    2017-05-04

    Background It is well established that mitochondrial damage plays a role in the pathophysiology of Alzheimer's disease (AD). However, studies carried out in humans barely contemplate regional differences with disease progression. Objective To study the expression of selected nuclear genes encoding subunits of the mitochondrial complexes and the activity of mitochondrial complexes in AD, in two regions: the entorhinal cortex (EC) and frontal cortex area 8 (FC). Methods Frozen samples from 148 cases processed for gene expression by qRT-PCR and determination of individual activities of mitochondrial complexes I, II, IV and V using commercial kits and home-made assays. Results Decreased expression of NDUFA2, NDUFB3, UQCR11, COX7C, ATPD, ATP5L and ATP50, covering subunits of complex I, II, IV and V, occurs in total homogenates of the EC in AD stages V-VI when compared with stages I-II. However reduced activity of complexes I, II and V of isolated mitochondria occurs as early as stages I-II when compared with middle-aged individuals in the EC. In contrast, no alterations in the expression of the same genes and no alterations in the activity of mitochondrial complexes are found in the FC in the same series. Conclusion Different mechanisms of impaired energy metabolism may occur in AD, one of them, represented by the EC, is the result of primary and early alteration of mitochondria; the other one is probably the result, at least in part, of decreased functional input and is represented by hypo-metabolism in the FC in AD patients aged 86 or younger. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Lower Activation in Frontal Cortex and Posterior Cingulate Cortex Observed during Sex Determination Test in Early-Stage Dementia of the Alzheimer Type

    PubMed Central

    Rajmohan, Ravi; Anderson, Ronald C.; Fang, Dan; Meyer, Austin G.; Laengvejkal, Pavis; Julayanont, Parunyou; Hannabas, Greg; Linton, Kitten; Culberson, John; Khan, Hafiz; De Toledo, John; Reddy, P. Hemachandra; O’Boyle, Michael W.

    2017-01-01

    Face-labeling refers to the ability to classify faces into social categories. This plays a critical role in human interaction as it serves to define concepts of socially acceptable interpersonal behavior. The purpose of the current study was to characterize, what, if any, impairments in face-labeling are detectable in participants with early-stage clinically diagnosed dementia of the Alzheimer type (CDDAT) through the use of the sex determination test (SDT). In the current study, four (1 female, 3 males) CDDAT and nine (4 females, 5 males) age-matched neurotypicals (NT) completed the SDT using chimeric faces while undergoing BOLD fMRI. It was expected that CDDAT participants would have poor verbal fluency, which would correspond to poor performance on the SDT. This could be explained by decreased activation and connectivity patterns within the fusiform face area (FFA) and anterior cingulate cortex (ACC). DTI was also performed to test the association of pathological deterioration of connectivity in the uncinate fasciculus (UF) and verbally-mediated performance. CDDAT showed lower verbal fluency test (VFT) performance, but VFT was not significantly correlated to SDT and no significant difference was seen between CDDAT and NT for SDT performance as half of the CDDAT performed substantially worse than NT while the other half performed similarly. BOLD fMRI of SDT displayed differences in the left superior frontal gyrus and posterior cingulate cortex (PCC), but not the FFA or ACC. Furthermore, although DTI showed deterioration of the right inferior and superior longitudinal fasciculi, as well as the PCC, it did not demonstrate significant deterioration of UF tracts. Taken together, early-stage CDDAT may represent a common emerging point for the loss of face labeling ability. PMID:28588478

  12. Long-latency modulation of motor cortex excitability by ipsilateral posterior inferior frontal gyrus and pre-supplementary motor area

    PubMed Central

    Fiori, Francesca; Chiappini, Emilio; Soriano, Marco; Paracampo, Riccardo; Romei, Vincenzo; Borgomaneri, Sara; Avenanti, Alessio

    2016-01-01

    The primary motor cortex (M1) is strongly influenced by several frontal regions. Dual-site transcranial magnetic stimulation (dsTMS) has highlighted the timing of early (<40 ms) prefrontal/premotor influences over M1. Here we used dsTMS to investigate, for the first time, longer-latency causal interactions of the posterior inferior frontal gyrus (pIFG) and pre-supplementary motor area (pre-SMA) with M1 at rest. A suprathreshold test stimulus (TS) was applied over M1 producing a motor-evoked potential (MEP) in the relaxed hand. Either a subthreshold or a suprathreshold conditioning stimulus (CS) was administered over ipsilateral pIFG/pre-SMA sites before the TS at different CS-TS inter-stimulus intervals (ISIs: 40–150 ms). Independently of intensity, CS over pIFG and pre-SMA (but not over a control site) inhibited MEPs at an ISI of 40 ms. The CS over pIFG produced a second peak of inhibition at an ISI of 150 ms. Additionally, facilitatory modulations were found at an ISI of 60 ms, with supra- but not subthreshold CS intensities. These findings suggest differential modulatory roles of pIFG and pre-SMA in M1 excitability. In particular, the pIFG –but not the pre-SMA– exerts intensity-dependent modulatory influences over M1 within the explored time window of 40-150 ms, evidencing fine-tuned control of M1 output. PMID:27929075

  13. Inferior frontal cortex modulation with an acute dose of heroin during cognitive control.

    PubMed

    Schmidt, André; Walter, Marc; Gerber, Hana; Schmid, Otto; Smieskova, Renata; Bendfeldt, Kerstin; Wiesbeck, Gerhard A; Riecher-Rössler, Anita; Lang, Undine E; Rubia, Katya; McGuire, Philip; Borgwardt, Stefan

    2013-10-01

    Impairments in inhibitory control and in stimulus-driven attention are hallmarks of drug addiction and are associated with decreased activation in the right inferior frontal gyrus (IFG). Although previous studies indicate that the response inhibition function is impaired in abstinent heroin dependents, and that this is mediated by reduced IFG activity, it remains completely unknown whether and how an acute dose of heroin modulates IFG activity during cognitive control in heroin-dependent patients. This study investigates the acute effects of heroin administration on IFG activity during response inhibition and stimulus-driven attention in heroin-dependent patients. Using a cross-over, double-blind, placebo-controlled design, saline and heroin were administered to 26 heroin-dependent patients from stable heroin-assisted treatment, while performing a Go/No-Go event-related functional magnetic resonance imaging task to assess right IFG activity during motor response inhibition, as well as during oddball-driven attention allocation. Relative to saline, heroin significantly reduced right IFG activity during both successful response inhibition and oddball-driven attention allocation, whereas it did not change right IFG activity during response inhibition after correction for the effect of attention allocation. These heroin-induced effects were not related to changes in drug craving, state anxiety, behavioral performance, or co-consumption of psychostimulant drugs. This study demonstrates that heroin administration acutely impairs stimulus-driven attention allocation, as indicated by reduced IFG activity in response to infrequently presented stimuli, and does not specifically modulate IFG activity during response inhibition.

  14. Inferior Frontal Cortex Modulation with an Acute Dose of Heroin During Cognitive Control

    PubMed Central

    Schmidt, André; Walter, Marc; Gerber, Hana; Schmid, Otto; Smieskova, Renata; Bendfeldt, Kerstin; Wiesbeck, Gerhard A; Riecher-Rössler, Anita; Lang, Undine E; Rubia, Katya; McGuire, Philip; Borgwardt, Stefan

    2013-01-01

    Impairments in inhibitory control and in stimulus-driven attention are hallmarks of drug addiction and are associated with decreased activation in the right inferior frontal gyrus (IFG). Although previous studies indicate that the response inhibition function is impaired in abstinent heroin dependents, and that this is mediated by reduced IFG activity, it remains completely unknown whether and how an acute dose of heroin modulates IFG activity during cognitive control in heroin-dependent patients. This study investigates the acute effects of heroin administration on IFG activity during response inhibition and stimulus-driven attention in heroin-dependent patients. Using a cross-over, double-blind, placebo-controlled design, saline and heroin were administered to 26 heroin-dependent patients from stable heroin-assisted treatment, while performing a Go/No–Go event-related functional magnetic resonance imaging task to assess right IFG activity during motor response inhibition, as well as during oddball-driven attention allocation. Relative to saline, heroin significantly reduced right IFG activity during both successful response inhibition and oddball-driven attention allocation, whereas it did not change right IFG activity during response inhibition after correction for the effect of attention allocation. These heroin-induced effects were not related to changes in drug craving, state anxiety, behavioral performance, or co-consumption of psychostimulant drugs. This study demonstrates that heroin administration acutely impairs stimulus-driven attention allocation, as indicated by reduced IFG activity in response to infrequently presented stimuli, and does not specifically modulate IFG activity during response inhibition. PMID:23673865

  15. Is evaluation of humorous stimuli associated with frontal cortex morphology? A pilot study using facial micro-movement analysis and MRI.

    PubMed

    Juckel, Georg; Mergl, Roland; Brüne, Martin; Villeneuve, Isabelle; Frodl, Thomas; Schmitt, Gisela; Zetzsche, Thomas; Born, Christine; Hahn, Klaus; Reiser, Maximilian; Möller, Hans-Jürgen; Bär, Karl-Jürgen; Hegerl, Ulrich; Meisenzahl, Eva Maria

    2011-05-01

    Humour involves the ability to detect incongruous ideas violating social rules and norms. Accordingly, humour requires a complex array of cognitive skills for which intact frontal lobe functioning is critical. Here, we sought to examine the association of facial expression during an emotion inducing experiment with frontal cortex morphology in healthy subjects. Thirty-one healthy male subjects (mean age: 30.8±8.9 years; all right-handers) watching a humorous movie ("Mr. Bean") were investigated. Markers fixed at certain points of the face emitting high-frequency ultrasonic signals allowed direct measurement of facial movements with high spatial-temporal resolution. Magnetic resonance images of the frontal cortex were obtained with a 1.5-T Magnetom using a coronar T2- and protondensity-weighted Dual-Echo-Sequence and a 3D-magnetization-prepared rapid gradient echo (MPRAGE) sequence. Volumetric analysis was performed using BRAINS. Frontal cortex volume was partly associated with slower speed of "laughing" movements of the eyes ("genuine" or Duchenne smile). Specifically, grey matter volume was associated with longer emotional reaction time ipsilaterally, even when controlled for age and daily alcohol intake. These results lend support to the hypothesis that superior cognitive evaluation of humorous stimuli - mediated by larger prefrontal grey and white matter volume - leads to a measurable reduction of speed of emotional expressivity in normal adults.

  16. Chronic psychotropic drug treatment causes differential expression of Reelin signaling system in frontal cortex of rats.

    PubMed

    Fatemi, S Hossein; Reutiman, Teri J; Folsom, Timothy D

    2009-06-01

    Disruption of the Reelin and GABAergic signaling systems have been observed in psychiatric disorders including autism, schizophrenia, bipolar disorder, and major depression. Less is known of therapeutic interventions that may help ameliorate the effects of these disruptions. The current study investigated whether chronic administration of psychotropic medications (clozapine, fluoxetine, haloperidol, lithium, olanzapine, and valproic acid) used in the treatment of psychiatric disorders alters levels of Reelin, its receptor Vldlr, downstream molecules Gsk3 beta, Dab-1, and Gad65/67 in rat prefrontal cortex as measured by qRT-PCR and SDS-PAGE and western blotting. qRT-PCR revealed that mRNAs for Reelin, Vldlr, Dab-1, Gsk3 beta, and Gad65 were each significantly altered by at least one of the drugs tested, and in the case of Reelin, Dab-1, and Gsk3 beta, by multiple drugs. To verify our results, we also performed SDS-PAGE and western blotting experiments. Again, several of the protein products for Reelin, Vldlr, Dab-1, Gsk3 beta, Gad65, and Gad67 were also significantly altered by multiple drugs. The present results suggest that the Reelin signaling and GABAergic systems are affected by commonly used psychotropic medications. These changes may help explain the efficacy of these drugs and provide further support for the investigation of the Reelin and GABAergic signaling systems as therapeutic targets for the treatment of neuropsychiatric diseases.

  17. Attracting Dynamics of Frontal Cortex Ensembles during Memory-Guided Decision-Making

    PubMed Central

    Seamans, Jeremy K.; Durstewitz, Daniel

    2011-01-01

    A common theoretical view is that attractor-like properties of neuronal dynamics underlie cognitive processing. However, although often proposed theoretically, direct experimental support for the convergence of neural activity to stable population patterns as a signature of attracting states has been sparse so far, especially in higher cortical areas. Combining state space reconstruction theorems and statistical learning techniques, we were able to resolve details of anterior cingulate cortex (ACC) multiple single-unit activity (MSUA) ensemble dynamics during a higher cognitive task which were not accessible previously. The approach worked by constructing high-dimensional state spaces from delays of the original single-unit firing rate variables and the interactions among them, which were then statistically analyzed using kernel methods. We observed cognitive-epoch-specific neural ensemble states in ACC which were stable across many trials (in the sense of being predictive) and depended on behavioral performance. More interestingly, attracting properties of these cognitively defined ensemble states became apparent in high-dimensional expansions of the MSUA spaces due to a proper unfolding of the neural activity flow, with properties common across different animals. These results therefore suggest that ACC networks may process different subcomponents of higher cognitive tasks by transiting among different attracting states. PMID:21625577

  18. Mapping DNA methylation across development, genotype, and schizophrenia in the human frontal cortex

    PubMed Central

    Jaffe, Andrew E.; Gao, Yuan; Deep-Soboslay, Amy; Tao, Ran; Hyde, Thomas M.; Weinberger, Daniel R.; Kleinman, Joel E.

    2015-01-01

    DNA methylation (DNAm) is important in brain development, and potentially in schizophrenia. We characterized DNAm in prefrontal cortex from 335 non-psychiatric controls across the lifespan and 191 patients with schizophrenia, and identified widespread changes in the transition from prenatal to postnatal life. These DNAm changes manifest in the transcriptome, correlate strongly with a shifting cellular landscape, and overlap regions of genetic risk for schizophrenia. A quarter of published GWAS-suggestive loci (4,208/15,930, p<10−100) manifest as significant methylation quantitative trait loci (meQTLs), including 59.6% of GWAS-positive schizophrenia loci. We identified 2,104 CpGs that differ between schizophrenia patients and controls, enriched for genes related to development and neurodifferentiation. The schizophrenia-associated CpGs strongly correlate with changes related to the prenatal-postnatal transition and show slight enrichment for GWAS risk loci, while not corresponding to CpGs differentiating adolescence from later adult life. These data implicate an epigenetic component to the developmental origins of this disorder. PMID:26619358

  19. Propofol attenuates low-frequency fluctuations of resting-state fMRI BOLD signal in the anterior frontal cortex upon loss of consciousness.

    PubMed

    Liu, Xiaolin; Lauer, Kathryn K; Douglas Ward, B; Roberts, Christopher; Liu, Suyan; Gollapudy, Suneeta; Rohloff, Robert; Gross, William; Chen, Guangyu; Xu, Zhan; Binder, Jeffrey R; Li, Shi-Jiang; Hudetz, Anthony G

    2017-02-15

    Recent studies indicate that spontaneous low-frequency fluctuations (LFFs) of resting-state functional magnetic resonance imaging (rs-fMRI) blood oxygen level-dependent (BOLD) signals are driven by the slow (<0.1Hz) modulation of ongoing neuronal activity synchronized locally and across remote brain regions. How regional LFFs of the BOLD fMRI signal are altered during anesthetic-induced alteration of consciousness is not well understood. Using rs-fMRI in 15 healthy participants, we show that during administration of propofol to achieve loss of behavioral responsiveness indexing unconsciousness, the fractional amplitude of LFF (fALFF index) was reduced in comparison to wakeful baseline in the anterior frontal regions, temporal pole, hippocampus, parahippocampal gyrus, and amygdala. Such changes were absent in large areas of the motor, parietal, and sensory cortices. During light sedation characterized by the preservation of overt responsiveness and therefore consciousness, fALFF was reduced in the subcortical areas, temporal pole, medial orbital frontal cortex, cingulate cortex, and cerebellum. Between light sedation and deep sedation, fALFF was reduced primarily in the medial and dorsolateral frontal areas. The preferential reduction of LFFs in the anterior frontal regions is consistent with frontal to sensory-motor cortical disconnection and may contribute to the suppression of consciousness during general anesthesia.

  20. 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.

  1. Frontal Cortex Stimulation Reduces Vigilance to Threat: Implications for the Treatment of Depression and Anxiety.

    PubMed

    Ironside, Maria; O'Shea, Jacinta; Cowen, Philip J; Harmer, Catherine J

    2016-05-15

    The difficulty in treating mood disorders has brought about clinical interest in alternative treatments, such as transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC). However, the optimal parameters for stimulation and underlying mechanisms of action are unclear. Psychiatric treatments have acute effects on emotional processing that predict later therapeutic action. Such effects have been proposed as cognitive biomarkers for screening novel treatments for depression and anxiety. This study assessed the effect of tDCS on a battery of emotional processing measures sensitive to antidepressant action. To refine optimal stimulation parameters, DLPFC stimulation using two common electrode montages was compared with sham. Sixty healthy volunteers received 20 minutes of active or sham DLPFC stimulation before completing computerized emotional processing tasks, including a dot-probe measure of vigilance to threat. Relative to sham stimulation, participants receiving simultaneous anodal stimulation of left DLPFC and cathodal stimulation of right DLPFC (bipolar-balanced montage) showed reduced vigilance to threatening stimuli. There was no such significant effect when the cathode was placed on the supraorbital ridge (bipolar-unbalanced montage). There were no effects of tDCS on other measures of emotional processing. Our findings provide the first experimental evidence that modulating activity in the DLPFC reduces vigilance to threatening stimuli. This significant reduction in fear vigilance is similar to that seen with anxiolytic treatments in the same cognitive paradigm. The finding that DLPFC tDCS acutely alters the processing of threatening information suggests a potential cognitive mechanism that could underwrite treatment effects in clinical populations. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  2. The hAPP-YAC transgenic model has elevated UPS activity in the frontal cortex similar to Alzheimer's disease and Down's syndrome.

    PubMed

    Seo, Hyemyung; Isacson, Ole

    2010-09-01

    The ubiquitin-proteasome system (UPS) is critical for handling the intra-cellular load of abnormal and misfolded proteins in several neurodegenerative diseases. First, to determine the effects of the over-expression of human amyloid precursor protein (hAPP) on UPS, we measured proteasome activities using fluorescent substrates in the frontal cortex of hAPP-yeast artificial chromosome (YAC) transgenic (tg) mice (R1.40, hemizygous; Lamb, Nat Genet, 9, 4; 1995). Chymotrypsin and PGPH-like activities of proteasome were increased in frontal cortex of hAPP-YAC tg mice. These proteasome activities (both chymotrypsin and PGPH-like) were further increased by cholinergic stimulation in littermate control mice, but not in hAPP-YAC tg mice. Nerve growth factor (NGF) levels were decreased by hAPP over-expression in the frontal cortex and hippocampus of hAPP-YAC tg mice, and further decreased by M1 agonist treatment in the hippocampus of littermate control and hAPP-YAC tg mice. Interestingly, the frontal cortex (BA9 area) of Alzheimer's disease (AD) patients (Stage 3, n=11) and Down's syndrome (DS) patients (n=9) showed similar up-regulation of the UPS activities to those seen in hAPP-YAC tg mice. M1 agonist stimulation increased the activities of α-secretase, which were down-regulated by hAPP over-expression in the frontal cortex of hAPP-YAC tg mice. These results demonstrate that (i) hAPP-YAC tg mice have an up-regulation in the frontal cortex of the UPS similar to AD and DS patients; (ii) muscarinic stimulation increase UPS activities, increase secreted APP (APPs) levels, and decrease amyloid beta 42/40 ratio only in littermate controls, but not in hAPP-YAC tg mice. Taken together, these results suggest that both the adaptive reactions in the proteostatic network and pathological changes in AD and DS need to be considered in the future potential therapeutics. © 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry.

  3. A Bimodal Tuning Curve for Spatial Frequency Across Left and Right Human Orbital Frontal Cortex During Object Recognition

    PubMed Central

    Fintzi, Anat R.; Mahon, Bradford Z.

    2014-01-01

    Orbital frontal cortex (OFC) is known to play a role in object recognition by generating “first-pass” hypotheses about the identity of naturalistic images based on low spatial frequency (SF) information. These hypotheses are evaluated by more detailed (and slower) ventral visual pathway processes. While it has been suggested on theoretical grounds, it remains unknown whether OFC also receives postrecognition feedback about stimulus identity. We used a novel paradigm in the context of functional magnetic resonance imaging that permits the first few hundred milliseconds of object recognition to be spread out over 120 s. OFC shows a robust response to low and relatively high SFs, whereas ventral stream regions display unimodal response distributions shifted toward high SFs. These findings in OFC were modulated by hemisphere, with right OFC differentially responding to low SFs and left OFC differentially responding to high SFs. Psychophysical experiments confirmed that the same ranges of SFs preferred by ventral stream regions are critical for determining the accuracy and speed of object recognition. Our findings indicate that OFC accesses global form (low SF information, right OFC) and object identity (high SF information, left OFC), and suggest that OFC receives feedback about the accuracy of its initial hypothesis regarding stimulus identity. PMID:23307636

  4. Do defense styles of ego relate to volumes of orbito-frontal cortex in patients with obsessive-compulsive disorder?

    PubMed

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

    2011-06-01

    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. 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. 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. 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.

  5. 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

  6. 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

  7. [Analysis of Electroencephalogram Sample Entropy Measurement in Frontal Association Cortex Based on Heroin-induced Conditioned Place Preference in Rats].

    PubMed

    Huang, Lei; Pan, Qunwan; Zhu, Zaiman; Li, Jing; Gao, Chunfang; Li, Tian; Xu, Xiaoyan

    2015-04-01

    To explore the relationship between the drug-seeking behavior, motivation of conditioned place preference (CPP) rats and the frontal association cortex (FrA) electroencephalogram (EEG) sample entropy, we in this paper present our studies on the FrA EEG sample entropy of control group rats and CPP group rats, respectively. We invested different behavior in four situations of the rat activities, i. e. rats were staying in black chamber of videoed boxes, those staying in white chamber of videoed boxes, those shuttling between black-white chambers and those shuttling between white-black chambers. The experimental results showed that, compared with the control group rats, the FrA EEG sample entropy of CPP rats staying in black chamber of video box and shuttling between white-black chambers had no significant difference. However, sample entropy is significantly smaller (P < 0.01) when heroin-induced group rats stayed in white chamber of video box and shuttled between black-white chambers. Consequently, the drug-seeking behavior and motivation of CPP rats correlated closely with the EEG sample entropy changes.

  8. Differential gene expression in the nucleus accumbens and frontal cortex of lewis and Fischer 344 rats relevant to drug addiction.

    PubMed

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

    2011-03-01

    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.

  9. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Stress and corticosterone increase the readily releasable pool of glutamate vesicles in synaptic terminals of prefrontal and frontal cortex.

    PubMed

    Treccani, G; Musazzi, L; Perego, C; Milanese, M; Nava, N; Bonifacino, T; Lamanna, J; Malgaroli, A; Drago, F; Racagni, G; Nyengaard, J R; Wegener, G; Bonanno, G; Popoli, M

    2014-04-01

    Stress and glucocorticoids alter glutamatergic transmission, and the outcome of stress may range from plasticity enhancing effects to noxious, maladaptive changes. We have previously demonstrated that acute stress rapidly increases glutamate release in prefrontal and frontal cortex via glucocorticoid receptor and accumulation of presynaptic SNARE complex. Here we compared the ex vivo effects of acute stress on glutamate release with those of in vitro application of corticosterone, to analyze whether acute effect of stress on glutamatergic transmission is mediated by local synaptic action of corticosterone. We found that acute stress increases both the readily releasable pool (RRP) of vesicles and depolarization-evoked glutamate release, while application in vitro of corticosterone rapidly increases the RRP, an effect dependent on synaptic receptors for the hormone, but does not induce glutamate release for up to 20 min. These findings indicate that corticosterone mediates the enhancement of glutamate release induced by acute stress, and the rapid non-genomic action of the hormone is necessary but not sufficient for this effect.

  11. The Role of the Frontal and Parietal Cortex in Proactive and Reactive Inhibitory Control: A Transcranial Direct Current Stimulation Study.

    PubMed

    Cai, Ying; Li, Siyao; Liu, Jing; Li, Dawei; Feng, Zifang; Wang, Qiang; Chen, Chuansheng; Xue, Gui

    2016-01-01

    Mounting evidence suggests that response inhibition involves both proactive and reactive inhibitory control, yet its underlying neural mechanisms remain elusive. In particular, the roles of the right inferior frontal gyrus (IFG) and inferior parietal lobe (IPL) in proactive and reactive inhibitory control are still under debate. This study aimed at examining the causal role of the right IFG and IPL in proactive and reactive inhibitory control, using transcranial direct current stimulation (tDCS) and the stop signal task. Twenty-two participants completed three sessions of the stop signal task, under anodal tDCS in the right IFG, the right IPL, or the primary visual cortex (VC; 1.5 mA for 15 min), respectively. The VC stimulation served as the active control condition. The tDCS effect for each condition was calculated as the difference between pre- and post-tDCS performance. Proactive control was indexed by the RT increase for go trials (or preparatory cost), and reactive control by the stop signal RT. Compared to the VC stimulation, anodal stimulation of the right IFG, but not that of the IPL, facilitated both proactive and reactive control. However, the facilitation of reactive control was not mediated by the facilitation of proactive control. Furthermore, tDCS did not affect the intraindividual variability in go RT. These results suggest a causal role of the right IFG, but not the right IPL, in both reactive and proactive inhibitory control.

  12. A simultaneous modulation of reactive and proactive inhibition processes by anodal tDCS on the right inferior frontal cortex.

    PubMed

    Cunillera, Toni; Fuentemilla, Lluís; Brignani, Debora; Cucurell, David; Miniussi, Carlo

    2014-01-01

    Proactive and reactive inhibitory processes are a fundamental part of executive functions, allowing a person to stop inappropriate responses when necessary and to adjust performance in in a long term in accordance to the goals of a task. In the current study, we manipulate, in a single task, both reactive and proactive inhibition mechanisms, and we investigate the within-subjects effect of increasing, by means of anodal transcranial direct current stimulation (tDCS), the involvement of the right inferior frontal cortex (rIFC). Our results show a simultaneous enhancement of these two cognitive mechanisms when modulating the neural activity of rIFC. Thus, the application of anodal tDCS increased reaction times on Go trials, indicating a possible increase in proactive inhibition. Concurrently, the stop-signal reaction time, as a covert index of the inhibitory process, was reduced, demonstrating an improvement in reactive inhibition. In summary, the current pattern of results validates the engagement of the rIFC in these two forms of inhibitory processes, proactive and reactive inhibition and it provides evidence that both processes can operate concurrently in the brain.

  13. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Task-dependent and distinct roles of the temporoparietal junction and inferior frontal cortex in the control of imitation

    PubMed Central

    Obhi, Sukhvinder S.; Banissy, Michael J.; Santiesteban, Idalmis; Press, Clare; Catmur, Caroline; Bird, Geoffrey

    2015-01-01

    The control of neurological networks supporting social cognition is crucially important for social interaction. In particular, the control of imitation is directly linked to interaction quality, with impairments associated with disorders characterized by social difficulties. Previous work suggests inferior frontal cortex (IFC) and the temporoparietal junction (TPJ) are involved in controlling imitation, but the functional roles of these areas remain unclear. Here, transcranial direct current stimulation (tDCS) was used to enhance cortical excitability at IFC and the TPJ prior to the completion of three tasks: (i) a naturalistic social interaction during which increased imitation is known to improve rapport, (ii) a choice reaction time task in which imitation needs to be inhibited for successful performance and (iii) a non-imitative control task. Relative to sham stimulation, stimulating IFC improved the context-dependent control of imitation—participants imitated more during the social interaction and less during the imitation inhibition task. In contrast, stimulating the TPJ reduced imitation in the inhibition task without affecting imitation during social interaction. Neither stimulation site affected the non-imitative control task. These data support a model in which IFC modulates imitation directly according to task demands, whereas TPJ controls task-appropriate shifts in attention toward representation of the self or the other, indirectly impacting upon imitation. PMID:25481003

  15. Medial frontal cortex and anterior insula are less sensitive to outcome predictability when monetary stakes are higher.

    PubMed

    Stern, Emily R; Gonzalez, Richard; Welsh, Robert C; Taylor, Stephan F

    2014-10-01

    Prior research links greater activation of posterior medial frontal cortex (pMFC) and anterior insula (AI) with decreasing outcome predictability during decision making, as measured by decreasing probability for the more likely outcome out of two or increasing outcome variance. In addition to predictability, much work indicates that the magnitude or 'stakes' of the outcome is also important. Despite the interest in the neural correlates of these decision variables, it is unknown whether pMFC and AI are differentially sensitive to predictability when magnitude is varied. This study examined brain activity during decision making in relation to decreasing outcome predictability for low as compared with high magnitude decisions. For low magnitude decisions, reduced predictability of the outcome was associated with greater activity in pMFC and bilateral AI, replicating prior studies. In contrast, there was no relationship between predictability and brain activity for high magnitude decisions, which tended to elicit greater pMFC and AI activity than low magnitude decisions for more predictable outcomes. These data indicate that the relationship between outcome predictability and pMFC and AI activity during decision making depends on magnitude, and suggest that these regions may be responding to the motivational salience of the decision rather than predictability information per se.

  16. Task-dependent and distinct roles of the temporoparietal junction and inferior frontal cortex in the control of imitation.

    PubMed

    Hogeveen, Jeremy; Obhi, Sukhvinder S; Banissy, Michael J; Santiesteban, Idalmis; Press, Clare; Catmur, Caroline; Bird, Geoffrey

    2015-07-01

    The control of neurological networks supporting social cognition is crucially important for social interaction. In particular, the control of imitation is directly linked to interaction quality, with impairments associated with disorders characterized by social difficulties. Previous work suggests inferior frontal cortex (IFC) and the temporoparietal junction (TPJ) are involved in controlling imitation, but the functional roles of these areas remain unclear. Here, transcranial direct current stimulation (tDCS) was used to enhance cortical excitability at IFC and the TPJ prior to the completion of three tasks: (i) a naturalistic social interaction during which increased imitation is known to improve rapport, (ii) a choice reaction time task in which imitation needs to be inhibited for successful performance and (iii) a non-imitative control task. Relative to sham stimulation, stimulating IFC improved the context-dependent control of imitation-participants imitated more during the social interaction and less during the imitation inhibition task. In contrast, stimulating the TPJ reduced imitation in the inhibition task without affecting imitation during social interaction. Neither stimulation site affected the non-imitative control task. These data support a model in which IFC modulates imitation directly according to task demands, whereas TPJ controls task-appropriate shifts in attention toward representation of the self or the other, indirectly impacting upon imitation.

  17. 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.

  18. 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

  19. Excessive hemodynamic activity in the superior frontal cortex during the flanker task in children with attention deficit hyperactivity disorder.

    PubMed

    Suzuki, Kota; Okumura, Yasuko; Kita, Yosuke; Oi, Yuhei; Yamashita, Yushiro; Goto, Takaaki; Inagaki, Masumi

    2017-09-06

    Near-infrared spectroscopy studies in children with attention deficit hyperactivity disorder (ADHD) have shown excessive prefrontal activity responsible for coping with interference. However, it is possible that the previous results were influenced by verbal, reading, and memory developments. The flanker task is an interference task that does not require a verbal response, reading, or memorization. We examined activity in the superior frontal cortex (SFC) during the flanker task in 12 children with ADHD and 14 children with typical development using near-infrared spectroscopy. SFC activity was significantly greater in children with ADHD than in those with typical development. The results showed excessive interference coping activity in children with ADHD irrespective of verbal, reading, and memory development. Moreover, SFC activity was positively correlated with the inattention subscale score of the ADHD rating scale. We suggest that children with ADHD need greater SFC activation to cope with interference, and the inefficient mechanism is demanding and hard to sustain, which causes inattention symptoms of children with ADHD.

  20. Transcriptional network analysis in frontal cortex in Lewy body diseases with focus on dementia with Lewy bodies.

    PubMed

    Santpere, Gabriel; Garcia-Esparcia, Paula; Andres-Benito, Pol; Lorente-Galdos, Belen; Navarro, Arcadi; Ferrer, Isidro

    2017-03-21

    The present study investigates global transcriptional changes in frontal cortex area 8 in incidental Lewy Body disease (iLBD), Parkinson disease (PD) and Dementia with Lewy bodies (DLB). We identified different co-expressed gene sets associated with disease stages, and gene ontology categories enriched in gene modules and differentially expressed genes including modules or gene clusters correlated to iLBD comprising upregulated dynein genes and taste receptors, and down-regulated innate inflammation. Focusing on DLB, we found modules with genes significantly enriched in functions related to RNA and DNA production, mitochondria and energy metabolism, purine metabolism, chaperone and protein folding system, and synapses and neurotransmission (particularly the GABAergic system). The expression of more than fifty selected genes was assessed with RT-qPCR. Our findings provide, for the first time, evidence of molecular cortical alterations in iLBD and involvement of several key metabolic pathways and gene hubs in DLB which may underlie cognitive impairment and dementia. This article is protected by copyright. All rights reserved.

  1. 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

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

    PubMed

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

    2015-01-01

    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). 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. 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. 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 driving and non-driving conditions.

  3. 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

  4. Taurine restores the exploratory behavior following alcohol withdrawal and decreases BDNF mRNA expression in the frontal cortex of chronic alcohol-treated rats.

    PubMed

    Hansen, Alana Witt; Almeida, Felipe Borges; Bandiera, Solange; Pulcinelli, Rianne Remus; Fragoso, Ana Luiza Rodrigues; Schneider, Ricardo; Barros, Helena Maria Tannhauser; Gomez, Rosane

    2017-10-01

    Alcohol use disorder is an alarming health problem, and the withdrawal symptoms increase the risk of relapse. We have hypothesized that taurine, a multitarget substance acting as a gamma-aminobutyric acid A receptor (GABAAR) positive modulator and a partial inhibitor of N-methyl-d-aspartate (NMDA) glutamate receptors, may reduce the withdrawal symptoms or modify behaviors when combined with alcohol. Therefore, we investigated the effects of taurine on behavior in the open field test (OFT), the GABAAR α2 subunit and BDNF mRNA expression in the frontal cortex of rats after chronic alcohol treatment or upon withdrawal. Rats received alcohol 2g/kg (alcohol and withdrawal groups) or water (control group) twice daily by oral gavage for 28days. On day 29, the withdrawal rats received water instead of alcohol, and all groups were reallocated to receive 100mg/kg taurine or vehicle intraperitoneally, once a day for 5days. On day 33, the rats were exposed to OFT; 18h later, they were euthanized, and the frontal cortex was dissected for GABAAR α2 subunit detection and BDNF mRNA expression determination by real-time quantitative PCR. Taurine administration restored rearing behavior to the control levels in the withdrawal rats. Taurine also showed anxiolytic-like effects in control rats and did not change the behaviors in the chronic alcohol group. Chronic alcohol treatment or withdrawal did not change the GABAAR α2 subunit or BDNF mRNA expression in the frontal cortex, but taurine decreased the α2 subunit level in control rats and to the BDNF levels in the alcohol rat group. We conclude that taurine restored exploratory behavior after alcohol withdrawal but that this effect was not related to the GABAAR α2 subunit or BDNF mRNA expression in the frontal cortex of the rats. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. The R-enantiomer of citalopram counteracts escitalopram-induced increase in extracellular 5-HT in the frontal cortex of freely moving rats.

    PubMed

    Mørk, A; Kreilgaard, M; Sánchez, C

    2003-08-01

    The selective serotonin (5-HT) reuptake inhibitor, citalopram, is a racemic mixture of an S(+)- and R(-)-enantiomer, escitalopram and R-citalopram, respectively. The present study compares the effects of escitalopram, R-citalopram and citalopram on extracellular levels of 5-HT in the frontal cortex of freely moving rats. In addition, co-injection of escitalopram and R-citalopram (ratios 1:2 and 1:4) were assessed. In some experiments escitalopram and R-citalopram were infused into the frontal cortex by reverse microdialysis. Finally, the extracellular level of escitalopram in the frontal cortex was studied after administration of escitalopram alone or in combination with R-citalopram. Escitalopram (1.0-3.9 mg/kg, s.c.) produced a greater maximal increase in extracellular 5-HT than citalopram (2.0-8.0 mg/kg, s.c.). R-citalopram (15.6 mg/kg s.c.) did not affect the 5-HT levels. When co-injected, R-citalopram counteracted the escitalopram-induced increase in extracellular 5-HT levels. Local infusion of the two enantiomers into the frontal cortex produced a similar inhibitory response. R-citalopram did not influence the extracellular levels of escitalopram and therefore does not exert its effect via a pharmacokinetic interaction with escitalopram. In conclusion, the 5-HT-reuptake inhibitory activity of citalopram resides in escitalopram, and the R-enantiomer counteracts this effect. This observation would predict an improved clinical profile of escitalopram compared to citalopram.

  6. Is the right frontal cortex really crucial in the mentalizing network? A longitudinal study in patients with a slow-growing lesion.

    PubMed

    Herbet, Guillaume; Lafargue, Gilles; Bonnetblanc, François; Moritz-Gasser, Sylvie; Duffau, Hugues

    2013-01-01

    Assessing the subjective experience of others in terms of mental states, a brain function referred to as mentalizing, is achieved in the brain through a set of low-level perceptual and high-level inference-based processes. Because of its recurrent implication in fMRI studies, the right frontal cortex, especially in its inferolateral and dorsomesial parts, is posited to be a "core system" in the sustenance of these neurocognitive mechanisms. In this context, we reasoned that if the right frontal cortex is really crucial for mentalizing, its surgical resection, following diffuse low-grade glioma invasion, should induce irreversible impairments. To test this hypothesis, we designed a longitudinal experimental setup in which ten patients harboring a low-grade glioma in right frontal areas were assessed just before, immediately after and three months after a brain surgery. Two well-validated behavioral tasks, thought to evaluate both aspects of mentalizing, were administered. The results obtained provide evidence that widespread surgical excisions of the right prefrontal cortex do not induce a long-term worsening of both aspects of mentalizing, although some transitory effects are observed immediately after the surgery. They suggest also for the first time in the same sample of patients a possible double functional dissociation between low-level perceptual (posterior inferolateral prefrontal) and high-level inference-based (dorsomesial prefrontal) mentalizing processes. This overall finding challenges the traditional view according to which the right frontal cortex is an "essential cortical node" in the mentalizing network since it might be expected that massive surgical excisions of this brain area would have induced more definitive impairments.

  7. 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.

  8. Age-related changes of brain iron load changes in the frontal cortex in APPswe/PS1ΔE9 transgenic mouse model of Alzheimer's disease.

    PubMed

    Xian-hui, Dong; Wei-juan, Gao; Tie-mei, Shao; Hong-lin, Xie; Jiang-tao, Bai; Jing-yi, Zhao; Xi-qing, Chai

    2015-04-01

    Alzheimer's disease (AD) as a neurodegenerative brain disorder is a devastating pathology leading to disastrous cognitive impairments and dementia, associated with major social and economic costs to society. Iron can catalyze damaging free radical reactions. With age, iron accumulates in brain frontal cortex regions and may contribute to the risk of AD. In this communication, we investigated the age-related brain iron load changes in the frontal cortex of 6- and 12-month-old C57BL/6J (C57) and APPswe/PS1ΔE9 (APP/PS1) double transgenic mouse by using graphite furnace atomic absorption spectrometry (GFAAS) and Perls' reaction. In the present study, we also evaluated the age-related changes of DMT1 and FPN1 by using Western blot and qPCR. We found that compared with 6-month-old APP/PS1 mice and the 12-month-old C57 mice, the 12-month-old APP/PS1 mice had increased iron load in the frontal cortex. The levels of DMT1 were significantly increased and the FPN1 were significantly reduced in the frontal cortex of the 12-month-old APP/PS1 mice than that in the 6-month-old APP/PS1 mice and 12-month-old C57 mice. We conclude that in AD damage occurs in conjunction with iron accumulation, and the brain iron load associated with loss control of the brain iron metabolism related protein DMT1 and FPN1 expressions.

  9. 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.

  10. [Effect of semax on the temporary dynamics of brain-derived neurotrophic factor and nerve growth factor gene expression in the rat hippocampus and frontal cortex].

    PubMed

    Agapova, T Iu; Agniullin, Ia V; Silachev, D N; Shadrina, M I; Slominskiĭ, P A; Shram, S I; Limborskaia, S A; Miasoedov, N F

    2008-01-01

    Semax is a synthetic peptide, which consists of the N-terminal adrenocorticotropic hormone fragment (4-7) (ACTH4-7) and C-terminal Pro-Gly-Pro peptide. Semax promotes neuron survival in hypoxia, increases selective attention and memory storage. It was shown that this synthetic peptide exerted a number of gene expressions, especially brain derived neurotrophic factor gene (Bdnf) and nerve growth factor gene (Ngf). Temporary dynamics of Bdnf and Ngf ex- pression in rat hippocampus and frontal cortex under Semax action (50 mg/kg, single intranasal administration) was studied in this work. It was shown that the studied gene expression levels changed significantly both in the hippocampus and the frontal cortex tissues 20 minutes after the peptide preparation application. The expression levels decreased in the hippocampus and increased in the frontal cortex. Forty minutes after Semax administration both gene expression levels returned to the level typical of control tissues. After that they increased significantly by 90 minutes after experiment start. Bdnf and Ngf expression levels decreased up to the control levels by 8 hours after medicine applying maximum gene expression levels were attained. Thus, Semax administration results in rapid, long-term, and specific activation of Bdnf and Ngf expression changes in different rat brain departments.

  11. Grape juice increases the BDNF levels but not alter the S100B levels in hippocampus and frontal cortex from male Wistar Rats.

    PubMed

    Dani, Caroline; Andreazza, Ana Cristina; Gonçalves, Carlos Alberto; Kapizinski, Flávio; Henriques, João A P; Salvador, Mirian

    2017-03-02

    Several studies have shown that a high consumption of vegetables and fruits is consistently associated with a low risk of oxidative stress-induced diseases, which includes some degenerative diseases such as amyotrophic lateral sclerosis, Alzheimer and Parkinson. Therefore, the objective of this study is to verify the effects of conventional and organic grape juice in the modulation of the neurotrophic factor (BDNF) and astrocytic markers protein (S100B) in hippocampus and frontal cortex of Wistar rats. In this study, 24 male Wistar rats were divided into three groups. To the first one, it was given organic purple grape juice; to the second, conventional grape juice, while the last one received only saline. After 30 days, all rats were sacrificed and hippocampus and frontal cortex were dissected. The animals that received organic and conventional grape juice showed, in frontal cortex, an elevated BNDF levels in relation to saline group. However, S100B levels did not change. These results showed that grape juices are able to modulate important marker in brain tissue, and could be an important factor to prevent brain diseases.

  12. Influence of age on aluminum induced lipid peroxidation and neurolipofuscin in frontal cortex of rat brain: a behavioral, biochemical and ultrastructural study.

    PubMed

    Tripathi, Sandeep; Mahdi, Abbas Ali; Nawab, Akbar; Chander, Ramesh; Hasan, Mahdi; Siddiqui, Mohammad Shakil; Mahdi, Farzana; Mitra, Kalyan; Bajpai, Virendra Kumar

    2009-02-09

    Aluminum exposure is known to be associated with oxidative stress and cognitive decline in experimental animals but the precise mechanism of its neurotoxicity has not yet been delineated. The present study attempts to assess the learning and memory capacity of rats using Y-maze test for cognitive functioning. The markers of oxidative stress, e.g. lipid peroxides and endogenous antioxidants as well as metals (Al, Fe, Cu, Zn and Se) were measured in the brain frontal cortex of young and aged rats fed with AlCl(3) (100 mg/kg b.w.) for 90 days and normal saline treated controls. We observed significant changes between young and aged Al treated rats and their controls in terms of lipid peroxides and endogenous antioxidants. Lipofuscin content was significantly increased in Al treated aged rats along with higher concentration of Al, Fe and Zn with concomitantly low levels of Cu, and Se. Ultrastructural studies of the frontal cortex of exposed rats revealed that the changes were more pronounced in the aged treated rats in terms of presence of spongiform lipofuscin, vacuolization and lysosomal degradation. Changes in synaptic morphology and decreased number of synapses were detected in the frontal cortex of Al treated aged rats. On the basis of the results of the present study, we conclude that Al may be linked with neurolipofuscinogenesis and alteration in neurobehavioral activity and these changes may be responsible for the development of age related disorders, such as Alzheimer's disease.

  13. 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

    2015-10-05

    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. 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.

  15. Chronic corticosterone decreases brain-derived neurotrophic factor (BDNF) mRNA and protein in the hippocampus, but not in the frontal cortex, of the rat.

    PubMed

    Jacobsen, Jacob P R; Mørk, Arne

    2006-09-19

    This study examined the effects of chronic corticosterone (32 mg/kg/day, s.c., 21 days) on brain-derived neurotrophic factor (BDNF) mRNA and protein in the frontal cortex and hippocampus of the rat. Because evidence suggests that BDNF is an important determinant of the function of the 5-hydroxytryptamine (5-HT) system, we also quantified tissue levels of 5-HT and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), to investigate if changes in BDNF mRNA and protein paralleled changes in the 5-HT system. Corticosterone modestly decreased BDNF protein (-16.6%) in whole hippocampus and BDNF mRNA (-19%) in the CA3 area. In contrast, BDNF mRNA and protein in the frontal cortex were unchanged. In both the frontal cortex and hippocampus, tissue levels of 5-HT and 5-HIAA were increased and decreased, respectively. Combined, these data suggests that the effects of corticosterone on the BDNF system are not linked to the effects on the 5-HT systems. However, our findings do suggest that chronic corticosterone impairs hippocampal BDNF function, a finding with potential relevance for the hippocampal atrophy reported in major depression. Additionally, as inferred from the alterations in tissue levels of 5-HT and 5-HIAA, chronic corticosterone may influence the function of the 5-HT system.

  16. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. 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

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

    PubMed

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

    2015-09-01

    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. Copyright © 2015 The Authors. Published by

  19. 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

  20. The right inferior frontal cortex in response inhibition: A tDCS-ERP co-registration study.

    PubMed

    Cunillera, Toni; Brignani, Debora; Cucurell, David; Fuentemilla, Lluís; Miniussi, Carlo

    2016-10-15

    In any given common situation, when an individual controls him/herself or obeys and stops a current action when asked to do, it is because the brain executes an inhibitory process. This ability is essential for adaptive behaviour, and it is also a requirement for accurate performance in daily life. It has been suggested that there are two main inhibitory functions related to behaviour, as inhibition is observed to affect behaviour at different time intervals. Proactive inhibition permits the subject to control his behavioural response over time by creating a response tendency, while reactive inhibition is considered to be a process that usually inhibits an already initiated response. In this context, it has been established that inhibitory function is implemented by specific fronto-basal-ganglia circuits. In the present study, we investigated the role of the right inferior frontal cortex (rIFC) in response inhibition by combining into a single task the Go-NoGo task and the Stop-Signal task. Concurrently, we applied transcranial direct current stimulation (tDCS) over the IFC and recorded electroencephalography (EEG). Thus, we obtained online EEG measurements of the tDCS-induced modifications in the IFC together with the participant's performance in a response inhibition task. We found that applying bilateral tDCS on the IFC (right anodal/left cathodal) significantly increased proactive inhibition, although the behavioural parameters indicative of reactive inhibition were unaffected by the stimulation. Finally, the inhibitory-P3 component reflected a similar modulation under both inhibitory conditions induced by the stimulation. Our data indicates that an online tDCS-ERP approach is achievable, but that a tDCS bilateral montage may not be the most efficient one for modulating the rIFC.

  1. Temporal Evolution of Target Representation, Movement Direction Planning, and Reach Execution in Occipital-Parietal-Frontal Cortex: An fMRI Study.

    PubMed

    Cappadocia, David C; Monaco, Simona; Chen, Ying; Blohm, Gunnar; Crawford, J Douglas

    2016-10-15

    The cortical mechanisms for reach have been studied extensively, but directionally selective mechanisms for visuospatial target memory, movement planning, and movement execution have not been clearly differentiated in the human. We used an event-related fMRI design with a visuospatial memory delay, followed by a pro-/anti-reach instruction, a planning delay, and finally a "go" instruction for movement. This sequence yielded temporally separable preparatory responses that expanded from modest parieto-frontal activation for visual target memory to broad occipital-parietal-frontal activation during planning and execution. Using the pro/anti instruction to differentiate visual and motor directional selectivity during planning, we found that one occipital area showed contralateral "visual" selectivity, whereas a broad constellation of left hemisphere occipital, parietal, and frontal areas showed contralateral "movement" selectivity. Temporal analysis of these areas through the entire memory-planning sequence revealed early visual selectivity in most areas, followed by movement selectivity in most areas, with all areas showing a stereotypical visuo-movement transition. Cross-correlation of these spatial parameters through time revealed separate spatiotemporally correlated modules for visual input, motor output, and visuo-movement transformations that spanned occipital, parietal, and frontal cortex. These results demonstrate a highly distributed occipital-parietal-frontal reach network involved in the transformation of retrospective sensory information into prospective movement plans. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. The cortical dynamics of speaking: Lexical and phonological knowledge simultaneously recruit the frontal and temporal cortex within 200 ms.

    PubMed

    Strijkers, Kristof; Costa, Albert; Pulvermüller, Friedemann

    2017-09-22

    Language production models typically assume that retrieving a word for articulation is a sequential process with substantial functional delays between conceptual, lexical, phonological and motor processing, respectively. Nevertheless, explicit evidence contrasting the spatiotemporal dynamics between different word production components is scarce. Here, using anatomically constrained magnetoencephalography during overt meaningful speech production, we explore the speed with which lexico-semantic versus acoustic-articulatory information of a to-be-uttered word become first neurophysiologically manifest in the cerebral cortex. We demonstrate early modulations of brain activity by the lexical frequency of a word in the temporal cortex and the left inferior frontal gyrus, simultaneously with activity in the motor and the posterior superior temporal cortex reflecting articulatory-acoustic phonological features (+LABIAL vs. +CORONAL) of the word-initial speech sounds (e.g., Monkey vs. Donkey). The specific nature of the spatiotemporal pattern correlating with a word's frequency and initial phoneme demonstrates that, in the course of speech planning, lexico-semantic and phonological-articulatory processes emerge together rapidly, drawing in parallel on temporal and frontal cortex. This novel finding calls for revisions of current brain language theories of word production. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Effects of cytotoxic deletions of somatic sensory cortex in fetal rats.

    PubMed

    Yurkewicz, L; Valentino, K L; Floeter, M K; Fleshman, J W; Jones, E G

    1984-01-01

    Pregnant rats were injected on the 14th day of gestation with the cytotoxic drug methylazoxymethanol acetate. This compound causes the death of neural precursor cells that were synthesizing DNA at the time of injection. After birth, the progeny of treated mothers grew to maturity with a neocortex that was greatly reduced in area by the death of all cells, particularly at the frontal and occipital poles but at medial and lateral margins of neocortex as well. In the remaining cortex layers II through IV failed to develop. The experiment deprived growing thalamocortical axons, which innervate the somatic sensory cortex late in development, of part of their normal target area and of a substantial number of their definitive target cells. It also deprived them of any cues they might have received from these target cells migrating through them as the axons accumulate beneath the cortical plate. Anatomical experiments indicated that, despite these defects, thalamocortical axons could still colonize the sensorimotor areas and form synapses in their typically bilaminar pattern, though the outer, denser lamina of terminations occurred abnormally at the level of the apices of layer V pyramidal cell bodies. Receptive field mapping of single and multiunit responses in the somatic sensory region showed brisk responses and receptive fields of normal size. It also indicated the formation of a body map that was topographically intact except for deletions at its periphery; that is, a total map was not compressed into a smaller area. This suggests that somatic sensory thalamocortical fibers recognize only remaining cortical target cells in appropriate fields. Moreover, successful ones among them seem to recognize neighborhood relations and conserve synaptic space at the expense of those that would have innervated the deleted peripheral parts of the area. Pyramidal neurons in the remaining cortical layers and in ectopic islands of cells that had incompletely migrated from the

  4. MT5-MMP Promotes Alzheimer’s Pathogenesis in the Frontal Cortex of 5xFAD Mice and APP Trafficking in vitro

    PubMed Central

    Baranger, Kévin; Bonnet, Amandine E.; Girard, Stéphane D.; Paumier, Jean-Michel; García-González, Laura; Elmanaa, Wejdane; Bernard, Anne; Charrat, Eliane; Stephan, Delphine; Bauer, Charlotte; Moschke, Katrin; Lichtenthaler, Stefan F.; Roman, François S.; Checler, Frédéric; Khrestchatisky, Michel; Rivera, Santiago

    2017-01-01

    We previously reported that deficiency of membrane-type five matrix metalloproteinase (MT5-MMP) prevents amyloid pathology in the cortex and hippocampus of 5xFAD mice, and ameliorates the functional outcome. We have now investigated whether the integrity of another important area affected in Alzheimer’s disease (AD), the frontal cortex, was also preserved upon MT5-MMP deficiency in 4-month old mice at prodromal stages of the pathology. We used the olfactory H-maze (OHM) to show that learning impairment associated with dysfunctions of the frontal cortex in 5xFAD was prevented in bigenic 5xFAD/MT5-MMP−/− mice. The latter exhibited concomitant drastic reductions of amyloid beta peptide (Aβ) assemblies (soluble, oligomeric and fibrillary) and its immediate precursor, C99. Simultaneously, astrocyte reactivity and tumor necrosis factor alpha (TNF-α) levels were also lowered. Moreover, MT5-MMP deficiency induced a decrease in N-terminal soluble fragments of amyloid precursor protein (APP), including soluble APPα (sAPPα), sAPPβ and the MT5-MMP-linked fragment of 95 kDa, sAPP95. However, the lack of MT5-MMP did not affect the activity of β- and γ-secretases. In cultured HEKswe cells, transiently expressed MT5-MMP localized to early endosomes and increased the content of APP and Aβ40 in these organelles, as well as Aβ levels in cell supernatants. This is the first evidence that the pro-amyloidogenic features of MT5-MMP lie, at least in part, on the ability of the proteinase to promote trafficking into one of the amyloidogenic subcellular loci. Together, our data further support the pathogenic role of MT5-MMP in AD and that its inhibition improves the functional and pathological outcomes, in this case in the frontal cortex. These data also support the idea that MT5-MMP could become a novel therapeutic target in AD. PMID:28119565

  5. Exposure to PM2.5 causes genetic changes in fetal rat cerebral cortex and hippocampus.

    PubMed

    Chao, Ming-Wei; Yang, Chin-Hua; Lin, Po-Ting; Yang, Yu-Hsiu; Chuang, Yu-Chen; Chung, Meng-Chi; Tseng, Chia-Yi

    2016-08-19

    PM2.5 travels along the respiratory tract and enters systemic blood circulation. Studies have shown that PM2.5 increases the incidence of various diseases not only in adults but also in newborn infants. It causes chronic inflammation in pregnant women and retards fetal development. In this study, pregnant rats were exposed to PM2.5 for extended periods of time and it was found that PM2.5 exposure increased immune cells in mother rats. In addition, cytokines and free radicals rapidly accumulated in the amniotic fluid and indirectly affected the fetuses. The authors collected cerebral cortex and hippocampus samples at E18 and analyzed changes of miRNA levels. Expression levels of cortical miR-6315, miR-3588, and miR-466b-5p were upregulated, and positively correlated with the genes Pkn2 (astrocyte migration), Gorab (neuritogenesis), and Mobp (allergic encephalomyelitis). In contrast, PM2.5 decreased expression of miR-338-5p and let-7e-5p, both related to mental development. Further, PM2.5 exposure increased miR-3560 and let-7b-5p in the hippocampus, two proteins that regulate genes Oxct1 and Lin28b that control ketogenesis and glycosylation, and neural cell differentiation, respectively. miR-99b-5p, miR-92b-5p, and miR-99a-5p were decreased, leading to reduced expression of Kbtbd8 and Adam11 which reduced cell mitosis, migration, and differentiation, and inhibited learning abilities and motor coordination of the fetus. © 2016 Wiley Periodicals, Inc. Environ Toxicol, 2016.

  6. Common and distinct brain regions in both parietal and frontal cortex support symbolic and nonsymbolic number processing in humans: A functional neuroimaging meta-analysis.

    PubMed

    Sokolowski, H Moriah; Fias, Wim; Mousa, Ahmad; Ansari, Daniel

    2017-02-01

    In recent years, there has been substantial growth in neuroimaging studies investigating neural correlates of symbolic (e.g. Arabic numerals) and non-symbolic (e.g. dot arrays) number processing. At present it remains contested whether number is represented abstractly, or if number representations in the brain are format-dependent. In order to quantitatively evaluate the available neuroimaging evidence, we used activation likelihood estimation (ALE) to conduct quantitative meta-analyses of the results reported in 57 neuroimaging papers. Consistent with the existence of an abstract representation of number in the brain, conjunction analyses revealed overlapping activation for symbolic and nonsymbolic numbers in frontal and parietal lobes. Consistent with the notion of format-dependent activation, contrast analyses demonstrated anatomically distinct fronto-parietal activation for symbolic and non-symbolic processing. Therefore, symbolic and non-symbolic numbers are subserved by format-dependent and abstract neural systems. Moreover, the present results suggest that regions across the parietal cortex, not just the intraparietal sulcus, are engaged in both symbolic and non-symbolic number processing, challenging the notion that the intraparietal sulcus is the key region for number processing. Additionally, our analyses indicate that regions in the frontal cortex subserve magnitude representations rather than non-numerical cognitive processes associated with number tasks, thereby highlighting the importance of considering both frontal and parietal regions as important for number processing. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Neuronal representation of task performance in the medial frontal cortex undergoes dynamic alterations dependent upon the demand for volitional control of action.

    PubMed

    Matsuzaka, Yoshiya; Akiyama, Tetsuya; Mushiake, Hajime

    2013-09-01

    Neural network contributing to forelimb task performance in the frontal cortex is dynamically reorganized by the necessity for volitional control of action. Neurons in the posterior medial prefrontal cortex (pmPFC) exhibit clear activity modulation when monkeys volitionally select the correct response tactic from multiple choices, but such activity disappears if selection of a tactic is unnecessary. Prompted by these results, we studied how the requirement to select an appropriate tactic affects the neural representation of action in downstream cortical areas. Two monkeys performed a spatial arm-reaching task with either left or right targets. The task required the monkeys to reach either toward (concordant trials) or away from (discordant trials) an illuminated target. Under the dual-tactic condition, concordant and discordant trials were randomly intermixed, requiring the selection of a response tactic. Under the single-tactic condition, only concordant trials were presented, allowing the monkeys to use the same tactic. Neurons in the pmPFC exhibited clear activity related to task performance under the former condition, but such activity disappeared under the latter condition. In contrast, neurons related to task performance were present under both conditions in supplementary motor area (SMA) and presupplementary motor area (pre-SMA). However, the efficacy of action representation by SMA but not pre-SMA neurons dramatically improved under the single-tactic condition. These results suggest that selection of the appropriate response tactic reorganizes neural circuits in specific motor areas in the medial frontal cortex, in addition to the pmPFC.

  8. Thalamic T-type Ca²+ channels mediate frontal lobe dysfunctions caused by a hypoxia-like damage in the prefrontal cortex.

    PubMed

    Kim, Jeongjin; Woo, Jeonghoon; Park, Young-Gyun; Chae, Sujin; Jo, Seonmi; Choi, Jeong Woo; Jun, Hong Young; Yeom, Young Il; Park, Seong Hoon; Kim, Kyung Hwan; Shin, Hee-Sup; Kim, Daesoo

    2011-03-16

    Hypoxic damage to the prefrontal cortex (PFC) has been implicated in the frontal lobe dysfunction found in various neuropsychiatric disorders. The underlying subcortical mechanisms, however, have not been well explored. In this study, we induced a PFC-specific hypoxia-like damage by cobalt-wire implantation to demonstrate that the role of the mediodorsal thalamus (MD) is critical for the development of frontal lobe dysfunction, including frontal lobe-specific seizures and abnormal hyperactivity. Before the onset of these abnormalities, the cross talk between the MD and PFC nuclei at theta frequencies was enhanced. During the theta frequency interactions, burst spikes, known to depend on T-type Ca(2+) channels, were increased in MD neurons. In vivo knockout or knockdown of the T-type Ca(2+) channel gene (Ca(V)3.1) in the MD substantially reduced the theta frequency MD-PFC cross talk, frontal lobe-specific seizures, and locomotor hyperactivity in this model. These results suggest a two-step model of prefrontal dysfunction in which the response to a hypoxic lesion in the PFC results in abnormal thalamocortical feedback driven by thalamic T-type Ca(2+) channels, which, in turn, leads to the onset of neurological and behavioral abnormalities. This study provides valuable insights into preventing the development of neuropsychiatric disorders arising from irreversible PFC damage.

  9. Modulation of oxidative stress, inflammation, autophagy and expression of Nrf2 in hippocampus and frontal cortex of rats fed with açaí-enriched diets.

    PubMed

    Poulose, Shibu M; Bielinski, Donna F; Carey, Amanda; Schauss, Alexander G; Shukitt-Hale, Barbara

    2017-06-01

    Açaí (Euterpe spp.), an exotic palm fruit, has recently emerged as a promising source of natural antioxidants with wide pharmacological and nutritional value. In this study, two different species of açaí pulp extracts, naturally grown in two distinct regions of the Amazon, namely, Euterpe oleracea Mart. (habitat: Brazilian floodplains of the Amazon) and Euterpe precatoria Mart. (habitat: Bolivian Amazon), were studied for their effects on brain health and cognition. Neurochemical analyses were performed in critical brain regions associated with memory and cognition of 19-month-old açaí-fed rats, in whom the cognitive benefits of açaí had been established. Results indicated significant reductions (P< 0.05) in prooxidant NADPH-oxidoreductase-2 (NOX2) and proinflammatory transcription factor NF-κB in açaí-fed rats. Measurement of Nrf2 expression, a transcription factor for antioxidant enzymes, and a possible link between oxidative stress, neuroinflammation and autophagy mechanisms, indicated significant overexpression (P<0.005) in the hippocampus and frontal cortex of the açaí-fed rats. Furthermore, significant activation of endogenous antioxidant enzymes GST and SOD were also observed in the açaí-fed animals when compared to control. Analysis of autophagy markers such as p62, phospho-mTOR, beclin1 and MAP1B-LC3 revealed differential expression in frontal cortex and hippocampus, mostly indicating an upregulation in the açaí-fed rats. In general, results were more profound for EP than EO in hippocampus as well as frontal cortex. Therefore, an açaí-enriched diet could possibly modulate Nrf2, which is known to modulate the intracellular redox status, thereby regulating the ubiquitin-proteosomal pathway, ultimately affecting cognitive function in the aging brain.

  10. 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

    2016-09-05

    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. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Social isolation stress and chronic glutathione deficiency have a common effect on the glutamine-to-glutamate ratio and myo-inositol concentration in the mouse frontal cortex.

    PubMed

    Corcoba, Alberto; Gruetter, Rolf; Do, Kim Q; Duarte, João M N

    2017-09-01

    Environmental stress can interact with genetic predisposition to increase the risk of developing psychopathology. In this work, we tested the hypothesis that social isolation stress interacts with impaired glutathione synthesis and have cumulative effects on the neurochemical profile of the frontal cortex. A mouse model with chronic glutathione deficit induced by knockout (-/-) of the glutamate-cysteine ligase modulatory subunit (Gclm) was exposed to social isolation stress from weaning to post-natal day 65. Using magnetic resonance methods at high-field (14.1 T), we analysed the neurochemical profile in the frontal cortex, brain size and ventricular volume of adult animals. Glutathione deficit was accompanied by elevated concentrations of N-acetylaspartate, alanine, and glutamine, as well as the ratio of glutamine-to-glutamate (Gln/Glu), and by a reduction in levels of myo-inositol and choline-containing compounds in the frontal cortex of -/- animals with respect to wild-type littermates. Although there was no significant interaction between social isolation stress and glutathione deficiency, mice reared in isolation displayed lower myo-inositol concentration (-8.4%, p < 0.05) and larger Gln/Glu (+7.6%, p < 0.05), relative to those in group housing. Furthermore, glutathione deficiency caused a reduction in whole brain volume and enlargement of ventricles, but social isolation had no effect on these parameters. We conclude that social isolation caused neurochemical alterations that may add to those associated to impaired glutathione synthesis. © 2017 International Society for Neurochemistry.

  12. Levels of Estrogen Receptors α and β in Frontal Cortex of Patients with Alzheimer’s Disease: Relationship to Mini-Mental State Examination Scores

    PubMed Central

    Kelly, Jeremiah F.; Bienias, Julia L.; Shah, Avni; Meeke, Kathleen A.; Schneider, Julie A.; Soriano, Edwin; Bennett, David A.

    2011-01-01

    Estrogen exerts beneficial effects on the brain throughout life. Studies demonstrate that estrogen is neuroprotective and that reduced brain estrogen activity may influence the clinical course of Alzheimer’s disease (AD). Changes in levels of estrogen receptors have been detected in postmortem brain tissue of AD patients. Very little is known about the relationship between clinical stage and levels of estrogen receptors in postmortem brain. We hypothesized that estrogen receptor levels would be related to severity of cognitive impairment assessed proximate to death. Western blotting was used to quantify ER-α and ER-β in nuclear, cytosolic, and crude membrane fractions of superior frontal cortex from 25 AD patients. Multiple linear regression analyses adjusted for age, sex, and education showed a significant linear relationship between Mini-Mental State Examination score (MMSE) and wild-type nuclear ER-α (â = 5.463, p = 0.03), but none between MMSE and wild-type nuclear ER-β (â = 2.29, p = 0.36). We incidentally observed additional higher and lower molecular mass bands for ER-α in study subjects. Additional experiments performed on frontal cortex nuclear fractions prepared from subjects enrolled in a different study confirmed that these same bands are present in female and males with and without AD. Together our data show a relationship between wild-type ER-α and level of cognitive impairment in AD, and also suggest the possibility that variant isoforms of ER-α may be present in frontal cortex of patients with and without AD. PMID:18288931

  13. Self-regulation therapy increases frontal gray matter in children with fetal alcohol spectrum disorder: evaluation by voxel-based morphometry

    PubMed Central

    Soh, Debra W.; Skocic, Jovanka; Nash, Kelly; Stevens, Sara; Turner, Gary R.; Rovet, Joanne

    2015-01-01

    Children with fetal alcohol spectrum disorder show executive function (EF) deficits, particularly in self-regulation skills, and abnormalities in brain regions critical for these skills. None of the validated EF interventions for these children has been evaluated with regards to impacts on brain structure. Twenty-nine children with FASD were assigned to either an immediate-treatment (TX) or delayed-treatment control (DTC) group (DTC). Nineteen typically developing children served as healthy controls (CT). All received a structural MRI scan and baseline neuropsychological testing, following which the TX group underwent 12 weekly 1.5-h sessions of the Alert Program for Self-Regulation®. After treatment or a period of ~14 weeks, all received a repeat scan and post-intervention testing. Whole-brain and region-of-interest analyses using voxel-based morphometry evaluated group differences and changes over time in gray matter (GM). Exploratory analyses revealed significant group changes: (1) At baseline, combined TX and DTC groups demonstrated global GM reductions compared with the CT group. (2) Region-of-interest analysis using a frontal mask, comparing post-intervention to pre-intervention results, showed significantly increased GM in the left middle frontal gyrus (BA10), right frontal pole (BA11), and right anterior cingulate (BA32) in the TX group. Similar results were not found in the DTC or CT groups. (3) At post-intervention, both TX and CT groups showed larger GM volumes than the DTC group in the left superior frontal gyrus (BA9), which was smaller in the FASD group at baseline. These results suggested that Alert led to improvements in post-intervention testing of self-regulation skills and typical brain development in treated children. PMID:25788884

  14. Chronic Administration of S-Allylcysteine Activates Nrf2 Factor and Enhances the Activity of Antioxidant Enzymes in the Striatum, Frontal Cortex and Hippocampus.

    PubMed

    Franco-Enzástiga, Úrzula; Santana-Martínez, Ricardo A; Silva-Islas, Carlos A; Barrera-Oviedo, Diana; Chánez-Cárdenas, María Elena; Maldonado, Perla D

    2017-06-24

    Oxidative stress plays an important role in neurodegenerative diseases and aging. The cellular defense mechanisms to deal with oxidative damage involve the activation of transcription factor related to NF-E2 (Nrf2), which enhances the transcription of antioxidant and phase II enzyme genes. S-allylcysteine (SAC) is an antioxidant with neuroprotective properties, and the main organosulfur compound in aged garlic extract. The ability of SAC to activate the Nrf2 factor has been previously reported in hepatic cells; however this effect has not been studied in normal brain. In order to determine if the chronic administration of SAC is able to activate Nrf2 factor and enhance antioxidant defense in the brain, male Wistar rats were administered with SAC (25, 50, 100 and 200 mg/kg-body weight each 24 h, i.g.) for 90 days. The activation of Nrf2, the levels of p65 and 8-hydroxy-2-deoxyguanosine (8-OHdG) as well as the activities of the enzymes glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST) were evaluated in the hippocampus, striatum and frontal cortex. Results showed that SAC activated Nrf2 factor in the hippocampus (25-200 mg/kg) and striatum (100 mg/kg) and significantly decreased p65 levels in the frontal cortex (25-200 mg/kg). On the other hand, SAC increased GPx, GR, CAT and SOD activities mainly in the hippocampus and striatum, but it did not change GST activity. Finally, no changes were observed in 8-OHdG levels mediated by SAC in any brain region, but the hippocampus showed a major level of 8-OHdG compared with the striatum and frontal cortex. All these results suggest that in the hippocampus, the observed increase in the activity of antioxidant enzymes could be associated with the ability of SAC to activate Nrf2 factor; however, a different mechanism could be involved in the striatum and frontal cortex, since no changes were found in Nrf2 activation and p65 levels.

  15. Regulation of a Truncated Form of Tropomyosin-Related Kinase B (TrkB) by Hsa-miR-185* in Frontal Cortex of Suicide Completers

    PubMed Central

    Maussion, Gilles; Yang, Jennie; Yerko, Volodymyr; Barker, Philip; Mechawar, Naguib; Ernst, Carl; Turecki, Gustavo

    2012-01-01

    Background TrkB-T1 is a BDNF receptor lacking a tyrosine kinase domain that is highly expressed in astrocytes and regulates BDNF-evoked calcium transients. Previous studies indicate that downregulation of TrkB-T1 in frontal cortex may be involved in neurobiological processes underlying suicide. Methods In a microarray screening study (N = 8), we interrogated all known microRNA in the frontal cortex of suicide completers with low expression of TrkB-T1 and normal controls. These findings were validated and followed up in a larger sample of cases and controls (N = 55). Functional analyses included microRNA silencing, microRNA overexpression and luciferase assays to investigate specificity and to validate interactions between differentially expressed microRNA and TrkB-T1. Results MicroRNAs Hsa-miR-185* and Hsa-miR-491-3p were upregulated in suicide completers with low expression of TrkB.T1 (Pnominal: 9.10−5 and 1.8.10−4 respectively; FDR-corrected p = 0.031). Bioinformatic analyses revealed five putative binding sites for the DiGeorge syndrome linked microRNA Hsa-miR-185*in the 3′UTR of TrkB-T1, but none for Hsa-miR-491-3P. The increase of Hsa-miR-185* in frontal cortex of suicide completers was validated then confirmed in a larger, randomly selected group of suicide completers, where an inverse correlation between Hsa-miR-185* and TrkB-T1 expression was observed (R = −0.439; p = 0.001). Silencing and overexpression studies performed in human cell lines confirmed the inverse relationship between hsa-mir-185* and trkB-T1 expression. Luciferase assays demonstrated that Hsa-miR-185* binds to sequences in the 3′UTR of TrkB-T1. Conclusion These results suggest that an increase of Hsa-miR-185* expression levels regulates, at least in part, the TrkB-T1 decrease observed in the frontal cortex of suicide completers and further implicate the 22q11 region in psychopathology. PMID:22802923

  16. Long-range functional interactions of anterior insula and medial frontal cortex are differently modulated by visuospatial and inductive reasoning tasks.

    PubMed

    Ebisch, Sjoerd J H; Mantini, Dante; Romanelli, Roberta; Tommasi, Marco; Perrucci, Mauro G; Romani, Gian Luca; Colom, Roberto; Saggino, Aristide

    2013-09-01

    The brain is organized into functionally specific networks as characterized by intrinsic functional relationships within discrete sets of brain regions. However, it is poorly understood whether such functional networks are dynamically organized according to specific task-states. The anterior insular cortex (aIC)-dorsal anterior cingulate cortex (dACC)/medial frontal cortex (mFC) network has been proposed to play a central role in human cognitive abilities. The present functional magnetic resonance imaging (fMRI) study aimed at testing whether functional interactions of the aIC-dACC/mFC network in terms of temporally correlated patterns of neural activity across brain regions are dynamically modulated by transitory, ongoing task demands. For this purpose, functional interactions of the aIC-dACC/mFC network are compared during two distinguishable fluid reasoning tasks, Visualization and Induction. The results show an increased functional coupling of bilateral aIC with visual cortices in the occipital lobe during the Visualization task, whereas coupling of mFC with right anterior frontal cortex was enhanced during the Induction task. These task-specific modulations of functional interactions likely reflect ability related neural processing. Furthermore, functional connectivity strength between right aIC and right dACC/mFC reliably predicts general task performance. The findings suggest that the analysis of long-range functional interactions may provide complementary information about brain-behavior relationships. On the basis of our results, it is proposed that the aIC-dACC/mFC network contributes to the integration of task-common and task-specific information based on its within-network as well as its between-network dynamic functional interactions.

  17. Folding, But Not Surface Area Expansion, Is Associated with Cellular Morphological Maturation in the Fetal Cerebral Cortex.

    PubMed

    Wang, Xiaojie; Studholme, Colin; Grigsby, Peta L; Frias, Antonio E; Cuzon Carlson, Verginia C; Kroenke, Christopher D

    2017-02-22

    Altered macroscopic anatomical characteristics of the cerebral cortex have been identified in individuals affected by various neurodevelopmental disorders. However, the cellular developmental mechanisms that give rise to these abnormalities are not understood. Previously, advances in image reconstruction of diffusion magnetic resonance imaging (MRI) have made possible high-resolution in utero measurements of water diffusion anisotropy in the fetal brain. Here, diffusion anisotropy within the developing fetal cerebral cortex is longitudinally characterized in the rhesus macaque, focusing on gestation day (G85) through G135 of the 165 d term. Additionally, for subsets of animals characterized at G90 and G135, immunohistochemical staining was performed, and 3D structure tensor analyses were used to identify the cellular processes that most closely parallel changes in water diffusion anisotropy with cerebral cortical maturation. Strong correlations were found between maturation of dendritic arbors on the cellular level and the loss of diffusion anisotropy with cortical development. In turn, diffusion anisotropy changes were strongly associated both regionally and temporally with cortical folding. Notably, the regional and temporal dependence of diffusion anisotropy and folding were distinct from the patterns observed for cerebral cortical surface area expansion. These findings strengthen the link proposed in previous studies between cellular-level changes in dendrite morphology and noninvasive diffusion MRI measurements of the developing cerebral cortex and support the possibility that, in gyroencephalic species, structural differentiation within the cortex is coupled to the formation of gyri and sulci.SIGNIFICANCE STATEMENT Abnormal brain morphology has been found in populations with neurodevelopmental disorders. However, the mechanisms linking cellular level and macroscopic maturation are poorly understood, even in normal brains. This study contributes new

  18. 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. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  19. 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

  20. Comparison of the temporary dynamics of NGF and BDNF gene expression in rat hippocampus, frontal cortex, and retina under Semax action.

    PubMed

    Shadrina, Maria; Kolomin, Timur; Agapova, Tamara; Agniullin, Yan; Shram, Stanislav; Slominsky, Petr; Lymborska, Svetlana; Myasoedov, Nikolay

    2010-05-01

    Neurotrophins are a family of structurally related proteins that regulate the survival, differentiation, and maintenance of function of different neuron populations. Some peptides are able to affect the production and activity of neurotrophins. One of these synthetic peptides is heptapeptide Semax, an analog of the N-terminal adrenocorticotropic hormone fragment 4-10. It is known that Semax has effects on learning and memory formation and exerts some neuroprotective effects in rodents and humans. Male Wistar rats were treated for 20 min, 40 min, 90 min, 3 h, 8 h, and 24 h with Semax. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) gene expression in rat brain and retina was analyzed by real-time polymerase chain reaction. It was revealed that after Semax administration the multidirectional activation of the expression of the genes under investigation in the hippocampus, frontal cortex, and retina was observed. The expression of both neurotrophin genes was decreased in rat hippocampus and retina 20 min after Semax administration and was increased in the frontal cortex. The expression levels of NGF remained practically constant in the retina at the initial stage, whereas the expression levels of BDNF were significantly increased 90 min after Semax administration.

  1. Severe Alterations in Lipid Composition of Frontal Cortex Lipid Rafts from Parkinson’s Disease and Incidental Parkinson’s Disease

    PubMed Central

    Fabelo, Noemí; Martín, Virginia; Santpere, Gabriel; Marín, Raquel; Torrent, Laia; Ferrer, Isidre; Díaz, Mario

    2011-01-01

    Lipid rafts are cholesterol- and sphingomyelin-enriched microdomains that provide a highly saturated and viscous physicochemical microenvironment to promote protein–lipid and protein–protein interactions. We purified lipid rafts from human frontal cortex from normal, early motor stages of Parkinson’s disease (PD) and incidental Parkinson’s disease (iPD) subjects and analyzed their lipid composition. We observed that lipid rafts from PD and iPD cortices exhibit dramatic reductions in their contents of n-3 and n-6 long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (22:6-n3) and arachidonic acid (20:4n-6). Also, saturated fatty acids (16:0 and 18:0) were significantly higher than in control brains. Paralleling these findings, unsaturation and peroxidability indices were considerably reduced in PD and iPD lipid rafts. Lipid classes were also affected in PD and iPD lipid rafts. Thus, phosphatidylserine and phosphatidylinositol were increased in PD and iPD, whereas cerebrosides and sulfatides and plasmalogen levels were considerably diminished. Our data pinpoint a dramatic increase in lipid raft order due to the aberrant biochemical structure in PD and iPD and indicate that these abnormalities of lipid rafts in the frontal cortex occur at early stages of PD pathology. The findings correlate with abnormal lipid raft signaling and cognitive decline observed during the development of these neurodegenerative disorders. PMID:21717034

  2. The mRNA expression of insulin-like growth factor-1 (Igf1) is decreased in the rat frontal cortex following gamma-hydroxybutyrate (GHB) administration.

    PubMed

    Brolin, Erika; Johansson, Jenny; Zelleroth, Sofia; Diwakarla, Shanti; Nyberg, Fred; Grönbladh, Alfhild; Hallberg, Mathias

    2017-02-26

    In recent years, growth hormone (GH), together with its secondary mediators insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-2 (IGF-2), have been highlighted for their beneficial effects in the central nervous system (CNS), in particular as cognitive enhancers. Cognitive processes, such as learning and memory, are known to be impaired in individuals suffering from substance abuse. In the present study, we investigated the effect of gamma-hydroxybuturate (GHB), an illicit drug used for its sedating and euphoric properties, on genes associated with the somatotrophic axis in regions of the brain important for cognitive function. Sprague Dawley rats (n=36) were divided into three groups and administered either saline, GHB 50mg/kg or GHB 300mg/kg orally for seven days. The levels of Ghr, Igf1 and Igf2 gene transcripts were analyzed using qPCR in brain regions involved in cognition and dependence. The levels of IGF-1 in blood plasma were also determined using ELISA. The results demonstrated a significant down-regulation of Igf1 mRNA expression in the frontal cortex in high-dose treated rats. Moreover, a significant correlation between Igf1 and Ghr mRNA expression was found in the hippocampus, the frontal cortex, and the caudate putamen, indicating local regulation of the GH/IGF-1 axis. To summarize, the current study concludes that chronic GHB treatment influences gene expression of Ghr and Igf1 in brain regions involved in cognitive function.

  3. 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.

  4. The Pursuit of DLPFC: Non-neuronavigated Methods to Target the Left Dorsolateral Pre-frontal Cortex With Symmetric Bicephalic Transcranial Direct Current Stimulation (tDCS).

    PubMed

    Seibt, Ole; Brunoni, Andre R; Huang, Yu; Bikson, Marom

    2015-01-01

    The dose of transcranial direct current stimulation (tDCS) is defined by electrode montage and current, while the resulting brain current flow is more complex and varies across individuals. The left dorsolateral pre-frontal cortex (lDLPFC) is a common target in neuropsychology and neuropsychiatry applications, with varied approaches used to experimentally position electrodes on subjects. To predict brain current flow intensity and distribution using conventional symmetrical bicephalic frontal 1 × 1 electrode montages to nominally target lDLPFC in forward modeling studies. Six high-resolution Finite Element Method (FEM) models were created from five subjects of varied head size and an MNI standard. Seven electrode positioning methods, nominally targeting lDLPFC, were investigated on each head model: the EEG 10-10 including F3-F4, F5-F6, F7-8, F9-F10, the Beam F3-System, the 5-5 cm-Rule and the developed OLE-System were evaluated as electrode positioning methods for 5 × 5 cm(2) rectangular sponge-pad electrodes. Each positioning approach resulted in distinct electrode positions on the scalp and variations in brain current flow. Variability was significant, but trends across montages and between subjects were identified. Factors enhancing electric field intensity and relative targeting in lDLPFC include increased inter-electrode distance and proximity to thinner skull structures. Brain current flow can be shaped, but not focused, across frontal cortex by tDCS montages, including intensity at lDLPFC. The OLE-system balances lDLPFC targeting and reduced electric field variability, along with clinical ease-of-use. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Repeated administration of desipramine and a GABAB receptor antagonist, CGP 36742, discretely up-regulates GABAB receptor binding sites in rat frontal cortex.

    PubMed Central

    Pratt, G. D.; Bowery, N. G.

    1993-01-01

    1. GABAB receptor binding site densities within laminar regions of the rat frontal cortex were examined autoradiographically following repeated administration (21 days) of the antidepressants desipramine, paroxetine and amitriptyline in addition to the GABAB receptor antagonists, CGP 35348 and CGP 36742. beta 1-Adrenoceptor autoradiography was studied in parallel with that for GABAB receptor sites. 2. The effects of these compounds were examined concomitantly on the GABAB receptor-mediated inhibition of forskolin- and enhancement of noradrenaline-stimulated cyclic AMP production. 3. GABAB receptor binding was increased by both desipramine (20 mg kg-1, p.o. and 10 mg kg-1, i.p.) and CGP 36742 (100 mg kg-1, i.p.) in the outer laminar region of the frontal cortex by around 50% above control levels. Conversely, no significant changes were mediated by paroxetine, amitriptyline, CGP 35348 or the GABAB receptor agonist, baclofen. 4. With the exception of paroxetine, all compounds down-regulated the total beta-adrenoceptor population throughout frontal cortical laminae which was attributable to the beta 1-adrenoceptor subtype. In contrast, the reduction in beta-adrenoceptors mediated by CGP 35348 and CGP 36742 did not occur as a consequence of reduced beta 1-adrenoceptor numbers. 5. Protracted treatment with CGP 35348, failed to influence forskolin-stimulated cyclic AMP production; however, a significant increase in the accumulation of cyclic AMP produced in response to forskolin was seen after treatment with CGP 36742. 6. Such discretely localized changes in GABAB receptor densities induced by desipramine and CGP 36742 may provide an explanation for the discrepancies reported in membrane binding studies and possibly implicate a role for GABAB receptor antagonists in antidepressant therapy. Images Figure 1 Figure 3 PMID:8242244

  6. Event-related induced frontal alpha as a marker of lateral prefrontal cortex activation during cognitive reappraisal

    PubMed Central

    Parvaz, Muhammad A.; MacNamara, Annmarie; Goldstein, Rita Z.; Hajcak, Greg

    2012-01-01

    Electrocortical activity, typically used to track the effects of cognitive reappraisal on the processing of emotional stimuli, has not been used to index PFC-mediated regulatory mechanisms responsible for these effects. In the current study, we examined the novel possibility that induced frontal alpha (i.e., 8 – 13 Hz), shown to reflect the inhibition and disengagement of task-relevant cortical regions, may be quantified to explore cortical activation that is specifically enhanced during cognitive reappraisal. For this purpose, 44 participants viewed unpleasant and neutral pictures followed by auditory instructions to either continue viewing the picture or reduce emotional response to the picture by making the picture seem less emotional (i.e., cognitive reappraisal). In line with previous work, unpleasant compared to neutral pictures elicited a larger late positive potential (LPP). Also corroborating previous work, the mid-latency LPP was reduced when pictures were cognitively reappraised. However, the current study showed for the first time that whereas unpleasant pictures elicited higher frontal alpha power than the neutral pictures bilaterally, frontal alpha power was reduced (indicative of more activation and cognitive control) during cognitive reappraisal of both picture types over the left hemisphere. Taken together, the LPP and event-related induced frontal alpha findings contribute unique information about distinct neural substrates and cognitive processes underlying reappraisal. PMID:22773414

  7. 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.

  8. 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

  9. The Iron Supplementation Dose for Perinatal Iron Deficiency Differentially Alters the Neurochemistry of Frontal Cortex and Hippocampus in Adult Rats

    PubMed Central

    Rao, Raghavendra; Tkac, Ivan; Unger, Erica L.; Ennis, Kathleen; Hurst, Amy; Schallert, Timothy; Connor, James; Felt, Barbara; Georgieff, Michael K.

    2013-01-01

    Background Long-term prefrontal cortex and hippocampus-based cognitive deficits are the sequelae of perinatal iron deficiency, despite iron supplementation starting in the newborn period. Whether high dose iron supplementation prevents these deficits is not known. Methods Perinatal iron deficiency was induced in rat pups using low-iron (3 mg/kg diet) diet during gestation until postnatal day (P) 8. Iron was supplemented using standard (40 mg/kg diet) or 10-fold higher (400 mg/kg diet) iron-containing diet until P21. Prefrontal cortex and hippocampal neurochemistry was determined using in vivo 1H nuclear magnetic resonance spectroscopy at 9.4 tesla on P90. Results Both iron supplementation doses corrected anemia and brain iron deficiency by P21. The neurochemical profile of the prefrontal cortex in both supplementation groups was comparable to the control group. In the hippocampus, standard-dose iron supplementation resulted in lower N-acetylaspartate and phosphoethanolamine, and higher N-acetylaspartylglutamate and glycerophosphocholine + phosphocholine concentrations. High-dose iron supplementation resulted in lower phosphoethanolamine and higher glycerophosphocholine + phosphocholine concentrations. Conclusions The iron supplementation dose for perinatal iron deficiency differentially alters the neurochemical profile of the prefrontal cortex and hippocampus in adulthood. The neurochemical changes suggest altered glutamatergic neurotransmission, hypomyelination and abnormal phospholipid metabolism in the formerly iron-deficient hippocampus. PMID:23095980

  10. The 5-HT(7) receptor antagonist SB 269970 counteracts restraint stress-induced attenuation of long-term potentiation in rat frontal cortex.

    PubMed

    Tokarski, K; Bobula, B; Kusek, M; Hess, G

    2011-12-01

    The effects of restraint lasting for 10 min, repeated twice daily for 3 days, were studied ex vivo in rat frontal cortex slices prepared 24 h after the last stress session. In slices originating from stressed animals, the amplitude of extracellular field potentials recorded in cortical layer II/III was increased. Stress also resulted in a reduced magnitude of long-term potentiation (LTP) of field potentials. In a separate experimental group, rats were subjected to restraint lasting for 10 min, twice daily for 3 days but, additionally, animals received injections of 5-HT(7) receptor antagonist SB 269970 (1.25 mg/kg) before each restraint stress session. In this group, the amplitude of field potentials and the magnitude of LTP were not different from the control, indicating that stress-induced modifications of basal glutamatergic transmission and synaptic plasticity were prevented by the 5-HT(7) receptor antagonist.

  11. Oleoylethanolamide prevents neuroimmune HMGB1/TLR4/NF-kB danger signaling in rat frontal cortex and depressive-like behavior induced by ethanol binge administration.

    PubMed

    Antón, María; Alén, Francisco; Gómez de Heras, Raquel; Serrano, Antonia; Pavón, Francisco Javier; Leza, Juan Carlos; García-Bueno, Borja; Rodríguez de Fonseca, Fernando; Orio, Laura

    2017-05-01

    Alcohol abuse is frequently characterized by a specific pattern of intake in binge drinking episodes, inducing neuroinflammation and brain damage. Here, we characterized the temporal profile of neuroinflammation in rats exposed to intragastric binge ethanol administrations (3 times/day × 4 days) and tested the anti-inflammatory/neuroprotective properties of the satiety factor oleoylethanolamide (OEA). Pre-treatment with OEA (5 mg/kg, i.p.) previous each alcohol gavage blocked the expression of high mobility group box 1 (HMGB1) danger signal and the innate immunity Toll-like receptors 4 (TLR4) in frontal cortex, and inhibited the nuclear factor-kappa B (NF-kB) proinflammatory cascade induced by alcohol binge administration. OEA reduced the levels of interleukin-1beta (IL-1β), the monocyte chemoattractant protein-1 (MCP-1), and the enzymes cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in ethanol binged animals. Elevations in plasma tumor necrosis factor alpha (TNF-α) and IL-1β after ethanol were also inhibited by OEA. OEA also prevented ethanol-induced lipid peroxidation, caspase-8 and pro-apoptotic caspase-3 activation in frontal cortex. Additionally, OEA blocked the rise in blood corticosterone levels after ethanol with no alteration in blood ethanol levels and may affect ethanol-induced gut permeability for endotoxin. Finally, OEA, administered as a pre-treatment during the ethanol binge, exerted antidepressant-like effects during acute withdrawal. Altogether, results highlight a beneficial profile of OEA as a potent anti-inflammatory, antioxidant, neuroprotective and antidepressant-like compound to treat alcohol abuse. © 2016 Society for the Study of Addiction.

  12. Venlafaxine treatment stimulates expression of brain-derived neurotrophic factor protein in frontal cortex and inhibits long-term potentiation in hippocampus.

    PubMed

    Cooke, J D; Grover, L M; Spangler, P R

    2009-09-15

    Antidepressant action may involve stimulation of brain-derived neurotrophic factor (BDNF). BDNF also regulates long-term potentiation (LTP). We hypothesized that the 5-HT and norepinephrine reuptake inhibitor, venlafaxine, would stimulate BDNF expression and alter LTP more effectively than the selective 5-HT reuptake inhibitor, citalopram. To test this, we administered venlafaxine or citalopram to rats for 1 or 3 weeks; control rats received vehicle only. We measured BDNF protein in hippocampal and frontal cortex homogenates, and serum. We assessed LTP in area cornu ammonis region 1 (CA1) of in vitro hippocampal brain slices. We also examined input/output function to determine if basal synaptic transmission in area CA1 was altered. Compared to vehicle control, frontal cortex BDNF protein was significantly greater after three, but not one, weeks of venlafaxine treatment. In contrast, citalopram (1 or 3 weeks) did not stimulate BDNF. The stimulatory effect of venlafaxine treatment on BDNF was superimposed on a general time-dependent decrease in expression which was seen in both vehicle control and citalopram-treated animals. LTP was significantly impaired in slices from venlafaxine-treated rats after both 1 and 3 weeks of treatment, but LTP appeared normal in slices from citalopram-treated and vehicle control rats. The LTP impairment caused by venlafaxine treatment was independent of changes in BDNF: LTP was impaired after only 1 week of treatment, prior to any effect on BDNF, and LTP magnitude was not correlated with BDNF protein concentration. Input/output function was significantly but equally reduced after 3 weeks of citalopram, venlafaxine, or control treatment. Decreased BDNF protein in citalopram and vehicle control animals, and decreased input/output function may be consequences of individual housing of animals, which we used to ensure proper dosing. Venlafaxine stimulation of BDNF and inhibition of LTP may be related to the reported effectiveness of

  13. Effective Connectivity between Ventral Occipito-Temporal and Ventral Inferior Frontal Cortex during Lexico-Semantic Processing. A Dynamic Causal Modeling Study.

    PubMed

    Perrone-Bertolotti, Marcela; Kauffmann, Louise; Pichat, Cédric; Vidal, Juan R; Baciu, Monica

    2017-01-01

    It has been suggested that dorsal and ventral pathways support distinct aspects of language processing. Yet, the full extent of their involvement and their inter-regional connectivity in visual word recognition is still unknown. Studies suggest that they might reflect the dual-route model of reading, with the dorsal pathway more involved in grapho-phonological conversion during phonological tasks, and the ventral pathway performing lexico-semantic access during semantic tasks. Furthermore, this subdivision is also suggested at the level of the inferior frontal cortex, involving ventral and dorsal parts for lexico-semantic and phonological processing, respectively. In the present study, we assessed inter-regional brain connectivity and task-induced modulations of brain activity during a phoneme detection and semantic categorization tasks, using fMRI in healthy subject. We used a dynamic causal modeling approach to assess inter-regional connectivity and task demand modulation within the dorsal and ventral pathways, including the following network components: the ventral occipito-temporal cortex (vOTC; dorsal and ventral), the superior temporal gyrus (STG; dorsal), the dorsal inferior frontal gyrus (dIFG; dorsal), and the ventral IFG (vIFG; ventral). We report three distinct inter-regional interactions supporting orthographic information transfer from vOTC to other language regions (vOTC -> STG, vOTC -> vIFG and vOTC -> dIFG) regardless of task demands. Moreover, we found that (a) during semantic processing (direct ventral pathway) the vOTC -> vIFG connection strength specifically increased and (b) a lack of modulation of the vOTC -> dIFG connection strength by the task that could suggest a more general involvement of the dorsal pathway during visual word recognition. Results are discussed in terms of anatomo-functional connectivity of visual word recognition network.

  14. Effective Connectivity between Ventral Occipito-Temporal and Ventral Inferior Frontal Cortex during Lexico-Semantic Processing. A Dynamic Causal Modeling Study

    PubMed Central

    Perrone-Bertolotti, Marcela; Kauffmann, Louise; Pichat, Cédric; Vidal, Juan R.; Baciu, Monica

    2017-01-01

    It has been suggested that dorsal and ventral pathways support distinct aspects of language processing. Yet, the full extent of their involvement and their inter-regional connectivity in visual word recognition is still unknown. Studies suggest that they might reflect the dual-route model of reading, with the dorsal pathway more involved in grapho-phonological conversion during phonological tasks, and the ventral pathway performing lexico-semantic access during semantic tasks. Furthermore, this subdivision is also suggested at the level of the inferior frontal cortex, involving ventral and dorsal parts for lexico-semantic and phonological processing, respectively. In the present study, we assessed inter-regional brain connectivity and task-induced modulations of brain activity during a phoneme detection and semantic categorization tasks, using fMRI in healthy subject. We used a dynamic causal modeling approach to assess inter-regional connectivity and task demand modulation within the dorsal and ventral pathways, including the following network components: the ventral occipito-temporal cortex (vOTC; dorsal and ventral), the superior temporal gyrus (STG; dorsal), the dorsal inferior frontal gyrus (dIFG; dorsal), and the ventral IFG (vIFG; ventral). We report three distinct inter-regional interactions supporting orthographic information transfer from vOTC to other language regions (vOTC -> STG, vOTC -> vIFG and vOTC -> dIFG) regardless of task demands. Moreover, we found that (a) during semantic processing (direct ventral pathway) the vOTC -> vIFG connection strength specifically increased and (b) a lack of modulation of the vOTC -> dIFG connection strength by the task that could suggest a more general involvement of the dorsal pathway during visual word recognition. Results are discussed in terms of anatomo-functional connectivity of visual word recognition network. PMID:28690506

  15. Brain region-specific decrease in the activity and expression of protein kinase A in the frontal cortex of regressive autism.

    PubMed

    Ji, Lina; Chauhan, Ved; Flory, Michael J; Chauhan, Abha

    2011-01-01

    Autism is a severe neurodevelopmental disorder that is characterized by impaired language, communication, and social skills. In regressive autism, affected children first show signs of normal social and language development but eventually lose these skills and develop autistic behavior. Protein kinases are essential in G-protein-coupled, receptor-mediated signal transduction and are involved in neuronal functions, gene expression, memory, and cell differentiation. We studied the activity and expression of protein kinase A (PKA), a cyclic AMP-dependent protein kinase, in postmortem brain tissue samples from the frontal, temporal, parietal, and occipital cortices, and the cerebellum of individuals with regressive autism; autistic subjects without a clinical history of regression; and age-matched developmentally normal control subjects. The activity of PKA and the expression of PKA (C-α), a catalytic subunit of PKA, were significantly decreased in the frontal cortex of individuals with regressive autism compared to control subjects and individuals with non-regressive autism. Such changes were not observed in the cerebellum, or the cortices from the temporal, parietal, and occipital regions of the brain in subjects with regressive autism. In addition, there was no significant difference in PKA activity or expression of PKA (C-α) between non-regressive autism and control groups. These results suggest that regression in autism may be associated, in part, with decreased PKA-mediated phosphorylation of proteins and abnormalities in cellular signaling.

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

    PubMed Central

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

    2016-01-01

    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. Seventy-two youth, ages 8 – 19 years, 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 preSMA decreased with age, whereas activation in dACC followed a non-linear (i.e., U-shaped) pattern in relation to age. In addition, connectivity of preSMA with anterior insula/frontal operculum (AI/FO) increased with age. These findings suggest differential development of preSMA and dACC sub-regions within the pMFC. Moreover, as children age, decreases in preSMA activation may couple with increases in preSMA-AI/FO connectivity to support gains in processing speed in response to demands for task control. PMID:27173761

  17. Brain Region–Specific Decrease in the Activity and Expression of Protein Kinase A in the Frontal Cortex of Regressive Autism

    PubMed Central

    Ji, Lina; Chauhan, Ved; Flory, Michael J.; Chauhan, Abha

    2011-01-01

    Autism is a severe neurodevelopmental disorder that is characterized by impaired language, communication, and social skills. In regressive autism, affected children first show signs of normal social and language development but eventually lose these skills and develop autistic behavior. Protein kinases are essential in G-protein-coupled, receptor-mediated signal transduction and are involved in neuronal functions, gene expression, memory, and cell differentiation. We studied the activity and expression of protein kinase A (PKA), a cyclic AMP–dependent protein kinase, in postmortem brain tissue samples from the frontal, temporal, parietal, and occipital cortices, and the cerebellum of individuals with regressive autism; autistic subjects without a clinical history of regression; and age-matched developmentally normal control subjects. The activity of PKA and the expression of PKA (C-α), a catalytic subunit of PKA, were significantly decreased in the frontal cortex of individuals with regressive autism compared to control subjects and individuals with non-regressive autism. Such changes were not observed in the cerebellum, or the cortices from the temporal, parietal, and occipital regions of the brain in subjects with regressive autism. In addition, there was no significant difference in PKA activity or expression of PKA (C-α) between non-regressive autism and control groups. These results suggest that regression in autism may be associated, in part, with decreased PKA-mediated phosphorylation of proteins and abnormalities in cellular signaling. PMID:21909354

  18. Hypermetabolic pattern in frontal cortex and other brain regions in unmedicated schizophrenia patients. Results from a FDG-PET study.

    PubMed

    Soyka, M; Koch, W; Möller, H J; Rüther, T; Tatsch, K

    2005-10-01

    We report results of a FDG-PET study in 10 patients with schizophrenia (6 unmedicated, 4 never medicated) and 12 healthy age-matched controls. The patients met ICD-10 and DSM-IV criteria for schizophrenia and all reported psychotic, "positive" symptoms when tested. Schizophrenic patients had higher absolute CMRGlu values in almost all quantified regions compared to normal subjects. Using the occipital cortex as the reference region patients showed a hyperfrontal metabolic pattern. Other significant regional differences were found with respect to thalamus, striatum and temporal cortex. The finding of a hyperfrontality in un- and never medicated psychotic schizophrenic patients must be discussed in the light of the psychopathological symptoms of patients when tested, a possible disruption of cortico-striato-thalamic feedback loops and recent findings of a hyperfrontality in experimentally induced psychosis (ketamine- and psilocybin-model of schizophrenia).

  19. The role of the orbitofrontal cortex in regulation of interpersonal space: evidence from frontal lesion and frontotemporal dementia patients.

    PubMed

    Perry, Anat; Lwi, Sandy J; Verstaen, Alice; Dewar, Callum; Levenson, Robert W; Knight, Robert T

    2016-12-01

    Interpersonal distance is central to communication and complex social behaviors but the neural correlates of interpersonal distance preferences are not defined. Previous studies suggest that damage to the orbitofrontal cortex (OFC) is associated with impaired interpersonal behavior. To examine whether the OFC is critical for maintaining appropriate interpersonal distance, we tested two groups of patients with OFC damage: Patients with OFC lesions and patients with behavioral variant frontotemporal dementia. These two groups were compared to healthy controls and to patients with lesions restricted to the dorsolateral prefrontal cortex. Only patients with OFC damage showed abnormal interpersonal distance preferences, which were significantly different from both controls and patients with dorsolateral prefrontal damage. The comfortable distances these patients chose with strangers were significantly closer than the other groups and resembled distances normally used with close others. These results shed light on the role of the OFC in regulating social behavior and may serve as a simple diagnostic tool for dementia or lesion patients.

  20. Evidence of diffuse damage in frontal and occipital cortex in the brain of patients with post-traumatic stress disorder.

    PubMed

    Tavanti, Maricla; Battaglini, Marco; Borgogni, Federico; Bossini, Letizia; Calossi, Sara; Marino, Daniela; Vatti, Gianpaolo; Pieraccini, Fulvio; Federico, Antonio; Castrogiovanni, Paolo; De Stefano, Nicola

    2012-02-01

    A number of MRI studies have shown focal or diffuse cortical gray matter (GM) abnormalities in patients with post-traumatic stress disorder (PTSD). However, the results of these studies are unclear regarding the cortical regions involved in this condition, perhaps due to the heterogeneity of the PTSD population included or to the differences in the methodology used for the quantification of the brain structures. In this study, we assessed differences in cortical GM volumes between a selected group of 25 drug-naive PTSD patients with history of adulthood trauma and 25 matched non-traumatized controls. Analyses were performed by using two different automated methods: the structural image evaluation using normalization of atrophy (SIENAX) and the voxel-based morphometry (VBM), as we trusted that if these complementary techniques provided similar results, it would increase the confidence in the validity of the assessment. Results of SIENAX and VBM analyses similarly showed that cortical GM volume decreases in PTSD patients when compared to healthy controls, particularly in the frontal and occipital lobes. These decreases seem to correlate with clinical measures. Our findings suggest that in drug-naïve PTSD patients with a history of adulthood trauma, brain structural damage is diffuse, with a particular prevalence for the frontal and occipital lobes, and is clinically relevant.

  1. Effects of implied physical effort in sensory-motor and pre-frontal cortex during language comprehension.

    PubMed

    Moody, Claire L; Gennari, Silvia P

    2010-01-01

    Embodied theories of conceptual knowledge suggest that sensory-motor representations of actions similar to those involved in the performance of the action described are recruited during language comprehension. The extent of this recruitment, however, and the brain mechanisms supporting this process remain unknown. Using fMRI, we investigated these issues by examining how people understand sentences that convey three different degrees of physical effort and by comparing this process to action execution. To understand the effort implied by the stimulus sentences, object and action properties associated with nouns and verbs respectively needed to be integrated: pushing the piano implies more physical effort than pushing the chair. Results indicated that a pre-motor region, which was also active in action execution, was sensitive to the degree of effort implied by the language. Interestingly, the anterior inferior frontal gyrus, a region typically associated with semantic processing, was not active in action execution but was nevertheless modulated by the effort implied. Inter-region correlations also suggested that this region was strongly correlated with pre-motor and posterior temporal regions. Overall, results suggest that (a) language understanding elicits action representations retaining a degree of specificity that was previously unsuspected, including unique properties of interactions with objects, and (b) these representations, which result from integrating the words' semantic information, may be computed within a collaborative neural network that includes the anterior inferior frontal gyrus.

  2. The relationship between the superior frontal cortex and alpha oscillation in a flanker task: Simultaneous recording of electroencephalogram (EEG) and near infrared spectroscopy (NIRS).

    PubMed

    Suzuki, Kota; Okumura, Yasuko; Kita, Yosuke; Oi, Yuhei; Shinoda, Haruo; Inagaki, Masumi

    2017-09-01

    Activity in the alpha band of the electroencephalogram (EEG) reflects functional inhibition of the cerebral cortex. The superior frontal cortex (SFC) is known to control alpha activity. Based on this relationship between SFC and alpha, we hypothesized that SFC controlled alpha mediates proactive control over interference. In this study, we examined the relationship between SFC and alpha in the flanker task by simultaneously recording EEG and near infrared spectroscopy (NIRS). Forty participants performed a flanker task with occasional (compatible 75%, incompatible 25%) and successive (incompatible 100%) conditions. In the occasional condition, larger SFC activity was related to pre-stimulus alpha enhancement under occipital electrodes. This is consistent with a model in which SFC enhances pre-stimulus alpha activity, leading to proactive control over interference. However, we could not detect a correlation between SFC activity and alpha activity in the successive condition. Active inhibition may have been reduced by a need to continuously inhibit brain regions associated with the irrelevant information. This may have reduced the role of the SFC in controlling alpha activity. Based on these findings, we postulate that there are two cerebral mechanisms of proactive control over interference. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  3. Selective reduction of cerebral cortex GABA neurons in a late gestation model of fetal alcohol spectrum disorder.

    PubMed

    Smiley, John F; Saito, Mariko; Bleiwas, Cynthia; Masiello, Kurt; Ardekani, Babak; Guilfoyle, David N; Gerum, Scott; Wilson, Donald A; Vadasz, Csaba

    2015-09-01

    Fetal alcohol spectrum disorders (FASD) are associated with cognitive and behavioral deficits, and decreased volume of the whole brain and cerebral cortex. Rodent models have shown that early postnatal treatments, which mimic ethanol toxicity in the third trimester of human pregnancy, acutely induce widespread apoptotic neuronal degeneration and permanent behavioral deficits. However, the lasting cellular and anatomical effects of early ethanol treatments are still incompletely understood. This study examined changes in neocortex volume, thickness, and cellular organization that persist in adult mice after postnatal day 7 (P7) ethanol treatment. Post mortem brain volumes, measured by both MRI within the skull and by fluid displacement of isolated brains, were reduced 10-13% by ethanol treatment. The cerebral cortex showed a similar reduction (12%) caused mainly by lower surface area (9%). In spite of these large changes, several features of cortical organization showed little evidence of change, including cortical thickness, overall neuron size, and laminar organization. Estimates of total neuron number showed a trend level reduction of about 8%, due mainly to reduced cortical volume but unchanged neuron density. However, counts of calretinin (CR) and parvalbumin (PV) subtypes of GABAergic neurons showed a striking >30% reduction of neuron number. Similar ethanol effects were found in male and female mice, and in C57BL/6By and BALB/cJ mouse strains. Our findings indicate that the cortex has substantial capacity to develop normal cytoarchitectonic organization after early postnatal ethanol toxicity, but there is a selective and persistent reduction of GABA cells that may contribute to the lasting cognitive and behavioral deficits in FASD.

  4. Selective reduction of cerebral cortex GABA neurons in a late gestation model of fetal alcohol spectrum disorder

    PubMed Central

    Smiley, John F.; Saito, Mariko; Bleiwas, Cynthia; Masiello, Kurt; Ardekani, Babak; Guilfoyle, David N.; Gerum, Scott; Wilson, Donald A.; Vadasz, Csaba

    2015-01-01

    Fetal alcohol spectrum disorders (FASD) are associated with cognitive and behavioral deficits, and decreased volume of the whole brain and cerebral cortex. Rodent models have shown that early postnatal treatments, which mimic ethanol toxicity in the third trimester of human pregnancy, acutely induce widespread apoptotic neuronal degeneration and permanent behavioral deficits. However, the lasting cellular and anatomical effects of early ethanol treatments are still incompletely understood. This study examined changes in neocortex volume, thickness, and cellular organization that persist in adult mice after postnatal day 7 (P7) ethanol treatment. Post mortem brain volumes, measured by both MRI within the skull and by fluid displacement of isolated brains, were reduced 10–13% by ethanol treatment. The cerebral cortex showed a similar reduction (12%) caused mainly by lower surface area (9%). In spite of these large changes, several features of cortical organization showed little evidence of change, including cortical thickness, overall neuron size, and laminar organization. Estimates of total neuron number showed a trend level reduction of about 8%, due mainly to reduced cortical volume but unchanged neuron density. However, counts of calretinin (CR) and parvalbumin (PV) subtypes of GABAergic neurons showed a striking >30% reduction of neuron number. Similar ethanol effects were found in male and female mice, and in C57BL/6By and BALB/cJ mouse strains. Our findings indicate that the cortex has substantial capacity to develop normal cytoarchitectonic organization after early postnatal ethanol toxicity, but there is a selective and persistent reduction of GABA cells that may contribute to the lasting cognitive and behavioral deficits in FASD. PMID:26252988

  5. 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

  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.

  7. The influence of fetal ethanol exposure on subsequent development of the cerebral cortex as revealed by magnetic resonance imaging.

    PubMed

    Leigland, Lindsey A; Ford, Matthew M; Lerch, Jason P; Kroenke, Christopher D

    2013-06-01

    . Additionally, regional patterns in cortical thickness differences suggested primary sensory areas were particularly vulnerable to gestational EtOH exposure. Structural MRI measurements were in accordance with previous histological studies performed in animal models of FASD. In addition to establishing a summary of MRI outcomes throughout development in FASD, this research suggests that MRI techniques are sufficiently sensitive to detect neuroanatomical effects of fetal EtOH exposure on development of the cerebral cortex during the period of time corresponding to late gestation in humans. Importantly, this research provides a link between animal histological data and human MRI data. Copyright © 2013 by the Research Society on Alcoholism.

  8. 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.

  9. 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Abnormalities of the Duo/Rac-1/PAK1 Pathway Drive Myosin Light Chain Phosphorylation in Frontal Cortex in Schizophrenia

    PubMed Central

    Rubio, María D.; Haroutunian, Vahram; Meador-Woodruff, James H.

    2012-01-01

    BACKGROUND Recent studies on GTPases have suggested that reduced Duo and Cdc42 transcript expression is involved in dendritic spine loss in schizophrenia. In murine models, Duo and Cdc42 phosphorylate PAK1, which modifies the activity of regulatory myosin light chain (MLC) and cofilin by altering their phosphorylation. Therefore, we hypothesized that in schizophrenia abnormal Duo and Cdc42 expression result in changes in MLC and/or cofilin phosphorylation, which may alter actin cytoskeleton dynamics underlying dendritic spine maintenance. METHODS We performed Western blot protein expression analysis in postmortem brains from patients diagnosed with schizophrenia and a comparison group. We focused our studies in the anterior cingulate cortex (ACC) (n=33 comparison group; n=36 schizophrenia) and dorsolateral prefrontal cortex (DLPFC) (n=29 comparison group; n=35 schizophrenia). RESULTS In both ACC and DLPFC, we found a reduction of Duo expression and PAK1 phosphorylation in schizophrenia. Cdc42 protein expression was decreased in ACC, but not in DLPFC. In ACC, we observed decreased PAK1 phosphorylation and increased MLC (pMLC) phosphorylation, while in DLPFC pMLC remained unchanged. DISCUSSION These data suggest a novel mechanism that may underlie dendritic spine loss in schizophrenia. The increase in pMLC seen in ACC may be associated with dendritic spine shrinkage. The lack of an effect on pMLC in DLPFC suggests that in schizophrenia PAK1 downstream pathways are differentially affected in these cortical areas. PMID:22458949

  11. The expression of thyroid hormone transporters in the human fetal cerebral cortex during early development and in N-Tera-2 neurodifferentiation.

    PubMed

    Chan, S-Y; Martín-Santos, A; Loubière, L S; González, A M; Stieger, B; Logan, A; McCabe, C J; Franklyn, J A; Kilby, M D

    2011-06-01

    Associations of neurological impairment with mutations in the thyroid hormone (TH) transporter, MCT8, and with maternal hypothyroxinaemia, suggest that THs are crucial for human fetal brain development. It has been postulated that TH transporters regulate the cellular supply of THs within the fetal brain during development. This study describes the expression of TH transporters in the human fetal cerebral cortex (7–20 weeks gestation) and during retinoic acid induced neurodifferentiation of the human N-Tera-2 (NT2) cell line, in triiodothyronine (T3) replete and T3-depleted media. Compared with adult cortex, mRNAs encoding OATP1A2, OATP1C1, OATP3A1 variant 2, OATP4A1, LAT2 and CD98 were reduced in fetal cortex at different gestational ages, whilst mRNAs encoding MCT8, MCT10, OATP3A1 variant 1 and LAT1 were similar. From the early first trimester, immunohistochemistry localised MCT8 and MCT10 to the microvasculature and to undifferentiated CNS cells. With neurodifferentiation, NT2 cells demonstrated declining T3 uptake, accompanied by reduced expressions of MCT8, LAT1, CD98 and OATP4A1. T3 depletion significantly reduced MCT10 and LAT2 mRNA expression at specific time points during neurodifferentiation but there were no effects upon T3 uptake, neurodifferentiation marker expression or neurite lengths and branching. MCT8 repression also did not affect NT2 neurodifferentiation. In conclusion, many TH transporters are expressed in the human fetal cerebral cortex from the first trimester, which could regulate cellular TH supply during early development. However, human NT2 neurodifferentiation is not dependent upon T3 or MCT8 and there were no compensatory changes to promote T3 uptake in a T3-depleted environment.

  12. Dynamic expression of calretinin in embryonic and early fetal human cortex

    PubMed Central

    González-Gómez, Miriam; Meyer, Gundela

    2014-01-01

    Calretinin (CR) is one of the earliest neurochemical markers in human corticogenesis. In embryos from Carnegie stages (CS) 17 to 23, calbindin (CB) and CR stain opposite poles of the incipient cortex suggesting early regionalization: CB marks the neuroepithelium of the medial boundary of the cortex with the choroid plexus (cortical hem). By contrast, CR is confined to the subventricular zone (SVZ) of the lateral and caudal ganglionic eminences at the pallial-subpallial boundary (PSB, or antihem), from where CR+/Tbr1- neurons migrate toward piriform cortex and amygdala as a component of the lateral cortical stream. At CS 19, columns of CR+ cells arise in the rostral cortex, and contribute at CS 20 to the “monolayer” of horizontal Tbr1+/CR+ and GAD+ cells in the preplate. At CS 21, the “pioneer cortical plate” appears as a radial aggregation of CR+/Tbr1+ neurons, which cover the entire future neocortex and extend the first corticofugal axons. CR expression in early human corticogenesis is thus not restricted to interneurons, but is also present in the first excitatory projection neurons of the cortex. At CS 21/22, the cortical plate is established following a lateral to medial gradient, when Tbr1+/CR- neurons settle within the pioneer cortical plate, and thus separate superficial and deep pioneer neurons. CR+ pioneer neurons disappear shortly after the formation of the cortical plate. Reelin+ Cajal-Retzius cells begin to express CR around CS21 (7/8 PCW). At CS 21–23, the CR+ SVZ at the PSB is the source of CR+ interneurons migrating into the cortical SVZ. In turn, CB+ interneurons migrate from the subpallium into the intermediate zone following the fibers of the internal capsule. Early CR+ and CB+ interneurons thus have different origins and migratory routes. CR+ cell populations in the embryonic telencephalon take part in a complex sequence of events not analyzed so far in other mammalian species, which may represent a distinctive trait of the initial

  13. Cholesterol and phospholipids in frontal cortex and synaptosomes of suicide completers: relationship with endosomal lipid trafficking genes.

    PubMed

    Freemantle, Erika; Mechawar, Naguib; Turecki, Gustavo

    2013-02-01

    Cholesterol (CHL) and phospholipid (PL) levels in synaptosomal membranes in particular can have an impact on cell signalling. Alterations in peripheral CHL measures have been consistently reported in suicidal behaviour. As CHL and PL turnover in the brain are important in synapse maintenance and function, the objective of this study was to determine if differences exist in synaptosomal cholesterol and phospholipid levels between suicide completers and controls. Expression measures of genes involved in lipid trafficking suggest an association between Lysosomal acid lipase A, cholesteryl ester hydrolase (LIPA) and brain PL levels, with LIPA being significantly increased in violent suicides and associated with alterations in brain PL. The results of this study suggest an altered PL content mediated by LIPA expression in violent suicides in the prefrontal cortex, which would have important consequences for inhibitory neurotransmission.

  14. ATPases enzyme activities during ageing in different types of somatic and synaptic plasma membranes from rat frontal cerebral cortex.

    PubMed

    Gorini, Antonella; Canosi, Umberto; Devecchi, Elisabetta; Geroldi, Diego; Villa, Roberto Federico

    2002-01-01

    The catalytic properties of energy-utilizing ATPases enzyme systems related to ions homeostasis were evaluated in different types of synaptic plasma membranes (SPM) and in somatic plasma membranes (SM) from cerebral cortex of rats aged 5, 10, and 22 months. The following enzymes were evaluated: Na+, K+-ATPase, Ca2+, Mg2+-ATPase, Mg2+-ATPase and the activity of acetylcholine esterase (AChE) was also evaluated. The ATPases located on SM and SPM and synaptic vesicles are involved in the regulation of presynaptic nerve ending homeostasis and postsynaptic activities. Different types of SM and SPM (three types) were obtained by combinations of differential and density gradient ultracentrifugation techniques in sucrose-Ficoll media: the first was obtained by purification of the sediment of mitochondrial supernate and the second after synaptosomal lysis and purification on density gradient. In the cerebral cortex of 5-month-old rats, the catalytic properties of ATPases systems markedly differ according to the different types of SPM and SM, thus indicating that the metabolic role of each ATPase is determined by their subcellular in vivo localization. As regards ageing: (i) ATPase enzyme catalytic activities tend to decrease during ageing in a complex way; (ii) ageing induced specific modifications in individual ATPases according to their subsynaptic localization; and (iii) these effects are probably due to specific biochemical situations that take place at each age, reflecting the bioenergetic state of the cerebral tissue with respect to the energy demand. The cerebral concentration and content of SM proteins were increased by ageing suggesting that many defective noncatalytic proteins may be formed during ageing, as shown by immunoblotting techniques.

  15. Updating existing emotional memories involves the frontopolar/orbito-frontal cortex in ways that acquiring new emotional memories does not.

    PubMed

    Sakaki, Michiko; Niki, Kazuhisa; Mather, Mara

    2011-11-01

    In life, we must often learn new associations to people, places, or things we already know. The current fMRI study investigated the neural mechanisms underlying emotional memory updating. Nineteen participants first viewed negative and neutral pictures and learned associations between those pictures and other neutral stimuli, such as neutral objects and encoding tasks. This initial learning phase was followed by a memory updating phase, during which participants learned picture-location associations for old pictures (i.e., pictures previously associated with other neutral stimuli) and new pictures (i.e., pictures not seen in the first phase). There was greater frontopolar/orbito-frontal (OFC) activity when people learned picture-location associations for old negative pictures than for new negative pictures, but frontopolar OFC activity did not significantly differ during learning locations of old versus new neutral pictures. In addition, frontopolar activity was more negatively correlated with the amygdala when participants learned picture-location associations for old negative pictures than for new negative or old neutral pictures. Past studies revealed that the frontopolar OFC allows for updating the affective values of stimuli in reversal learning or extinction of conditioning [e.g., Izquierdo, A., & Murray, E. A. Opposing effects of amygdala and orbital PFC lesions on the extinction of instrumental responding in macaque monkeys. European Journal of Neuroscience, 22, 2341-2346, 2005]; our findings suggest that it plays a more general role in updating associations to emotional stimuli.

  16. 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

  17. 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

    2016-04-14

    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.

  18. 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.

  19. 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. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Frontal cortex ablation reversibly decreases striatal zif/268 and junB expression: temporal correspondence with sensory neglect and its spontaneous recovery.

    PubMed

    Vargo, J M; Marshall, J F

    1996-04-01

    This study's goal is to identify subcortical adaptations that may contribute to recovery of function following cortical injury. After unilateral aspiration of the medial agranular region of frontal cortex (AGm), rats demonstrate neglect of contralateral stimuli and recover within 3-4 weeks. Previous studies indicate that compensatory neural alterations involving dopamine (DA) occur following this cortical injury and that recovery from neglect produced by frontal injury is accompanied by normalization of glucose utilization within subcortical structures including the basal ganglia. The current study examined Zif and JunB, IEG protein products constitutively expressed in striatum, rendering it possible to investigate the effects of unilateral AGm ablation on striatal function during unstimulated as well as amphetamine-stimulated conditions. Five days after surgery, when contralateral neglect was still evident, the numbers of Zif-like or Jun-like immunoreactive (IR) nuclei in the ipsilateral striata of AGm-ablated rats were reduced. These lesion effects were similar for both constitutive and amphetamine-stimulated IEG expression and were restricted to the dorsolateral caudate-putamen, where excitatory input from AGm is most dense. In contrast, 3 or more weeks after AGm ablation, in rats demonstrating recovery, normal striatal Zif- and JunB-like immunoreactivity occurred. Thus, striatal zif/268 and junB expression is reduced 5 days after AGm injury in rats demonstrating neglect and normalized 3 or more weeks later in recovered rats. These findings indicate that adaptations involving the striatal medium spiny neuron, a site of convergence of cortical glutamatergic and nigral dopaminergic afferents, may contribute to behavioral recovery following neocortical injury.

  1. Executive function relates to surface area of frontal and temporal cortex in very-low-birth-weight late teenagers.

    PubMed

    Østgård, Heidi Furre; Sølsnes, Anne Elisabeth; Bjuland, Knut Jørgen; Rimol, Lars Morten; Martinussen, Marit; Brubakk, Ann-Mari; Håberg, Asta Kristine; Skranes, Jon; Løhaugen, Gro Christine Christensen

    2016-04-01

    Being born with very low birth weight (VLBW; birth weight (BW) ≤1500 g) is associated with increased risk of maldevelopment of the immature brain which may affect neurological functioning. Deficits in attention and executive function problems have been reported in VLBW survivors compared with healthy subjects. The aim of this study was to evaluate attention and executive functions and to relate the clinical test results to cortical morphometry findings in VLBW young adults compared with term-born controls. Prospective follow-up study of three year cohorts of VLBW and control children from birth to adulthood. A comprehensive neuropsychological test battery was administered to 55 VLBW subjects born preterm (mean BW: 1217 g) and 81 term-born controls (mean BW: 3707 g) at age 19-20. Cerebral MRI was successfully obtained in 46 VLBW subjects and 61 controls. The FreeSurfer software package was applied for the cortical analyses based on T1-weighted MRI images. The VLBW group obtained inferior scores on 15 of the 29 neuropsychological measures assessing attention and executive function and on both the attention and executive function domain scores. We found positive correlations between the executive function domain score and cortical surface area, especially in the antero-medial frontal and the temporal lobes of the brain in the VLBW group. Young adults born with VLBW show deficits in attention and executive function compared with controls. The executive problems were related to smaller cortical surface area in brain regions known to be involved in higher order cognitive functioning. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. 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

  3. 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

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

    2016-02-10

    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 (1)H-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. 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 regions of the brain. Here

  4. Potentiation of barbiturate-induced alterations in presynaptic noradrenergic function in rat frontal cortex by imidazol(in)e α2-adrenoceptor agonists

    PubMed Central

    Dalley, J W; Parker, C A; Wülfert, E; Hudson, A L; Nutt, D J

    1998-01-01

    In order to resolve the extent to which presynaptic noradrenergic mechanisms contribute to the anaesthetic-sparing effects of α2-adrenoceptor agonists in vivo microdialysis was used to investigate the combined effects of sodium pentobarbitone and imidazol(in)e α2-adrenoceptor agonists on extracellular levels of noradrenaline (NA) in the rat frontal cortex.Dialysate levels of NA were markedly reduced by the addition of TTX (2 μM) or by the removal of calcium in the perfusate. These data imply that dialysate NA levels are ultimately dependent on exocytotic release mechanisms from afferent coeruleo-cortical neurones.Systemic administration of sodium pentobarbitone (85 mg kg−1, i.p.) induced general anaesthesia and reduced NA levels by 92% after 30 min. The restoration of basal levels 90 min later was closely associated with a return of the corneal blink reflex.Basal NA levels in conscious animals were not affected by an intravenous infusion of equally radioactive solutions of either imidazoline (clonidine) or imidazole (mivazerol) α2-adrenoceptor agonists. The dose rate employed for each compound was 2 μg kg−1 h−1 over 2 h.The co-administration of intravenous clonidine or mivazerol, each at 2 μg kg−1 h−1 for 2 h, with sodium pentobarbitone (85 mg kg−1, i.p.), produced a marked and prolonged reduction in NA efflux. After 2 h, NA levels remained suppressed by 95% (clonidine) and 80% (mivazerol) and animals remained deeply anaesthetized.The accumulation of tritium in brain tissue was 42–73% lower across all brain regions examined after [3H]-mivazerol administration than after [3H]-clonidine administration. Sodium pentobarbitone did not alter the accumulation of tritium in brain tissue after the administration of either α2-adrenoceptor agonist.These data demonstrate that α2-adrenoceptor agonists potentiate the inhibitory effects of sodium pentobarbitone on extracellular levels of NA in the frontal cortex. Further

  5. Impaired Activation of Visual Attention Network for Motion Salience Is Accompanied by Reduced Functional Connectivity between Frontal Eye Fields and Visual Cortex in Strabismic Amblyopia

    PubMed Central

    Wang, Hao; Crewther, Sheila G.; Liang, Minglong; Laycock, Robin; Yu, Tao; Alexander, Bonnie; Crewther, David P.; Wang, Jian; Yin, Zhengqin

    2017-01-01

    Strabismic amblyopia is now acknowledged to be more than a simple loss of acuity and to involve alterations in visually driven attention, though whether this applies to both stimulus-driven and goal-directed attention has not been explored. Hence we investigated monocular threshold performance during a motion salience-driven attention task involving detection of a coherent dot motion target in one of four quadrants in adult controls and those with strabismic amblyopia. Psychophysical motion thresholds were impaired for the strabismic amblyopic eye, requiring longer inspection time and consequently slower target speed for detection compared to the fellow eye or control eyes. We compared fMRI activation and functional connectivity between four ROIs of the occipital-parieto-frontal visual attention network [primary visual cortex (V1), motion sensitive area V5, intraparietal sulcus (IPS) and frontal eye fields (FEF)], during a suprathreshold version of the motion-driven attention task, and also a simple goal-directed task, requiring voluntary saccades to targets randomly appearing along a horizontal line. Activation was compared when viewed monocularly by controls and the amblyopic and its fellow eye in strabismics. BOLD activation was weaker in IPS, FEF and V5 for both tasks when viewing through the amblyopic eye compared to viewing through the fellow eye or control participants' non-dominant eye. No difference in V1 activation was seen between the amblyopic and fellow eye, nor between the two eyes of control participants during the motion salience task, though V1 activation was significantly less through the amblyopic eye than through the fellow eye and control group non-dominant eye viewing during the voluntary saccade task. Functional correlations of ROIs within the attention network were impaired through the amblyopic eye during the motion salience task, whereas this was not the case during the voluntary saccade task. Specifically, FEF showed reduced functional

  6. Improvement of Learning and Increase in Dopamine Level in the Frontal Cortex by Methylphenidate in Mice Lacking Dopamine Transporter

    PubMed Central

    Takamatsu, Y.; Hagino, Y.; Sato, A.; Takahashi, T.; Nagasawa, S.Y.; Kubo, Y.; Mizuguchi, M.; Uhl, G.R.; Sora, I.; Ikeda, K.

    2015-01-01

    The symptoms of attention-deficit/hyperactivity disorder (ADHD) are characterized by inattention and hyperactivity-impulsivity. It is a common childhood neurodevelopmental disorder that often persists into adulthood. Improvements in ADHD symptoms using psychostimulants have been recognized as a paradoxical calming effect. The psychostimulant methylphenidate (MPH) is currently used as the first-line medication for the management of ADHD. Recent studies have drawn attention to altered dopamine-mediated neurotransmission in ADHD, particularly reuptake by the dopamine transporter (DAT). This hypothesis is supported by the observation that DAT knockout mice exhibit marked hyperactivity that is responsive to acute MPH treatment. However, other behaviors relevant to ADHD have not been fully clarified. In the present study, we observed learning impairment in shuttle-box avoidance behavior together with hyperactivity in a novel environment in DAT knockout mice. Methylphenidate normalized these behaviors and enhanced escape activity in the tail suspension test. Interestingly, the effective dose of MPH increased extracellular dopamine in the prefrontal cortex but not striatum, suggesting an important role for changes in prefrontal dopamine in ADHD. Research that uses rodent models such as DAT knockout mice may be useful for elucidating the pathophysiology of ADHD. PMID:25817856

  7. Deficient reinforcement learning in medial frontal cortex as a model of dopamine-related motivational deficits in ADHD.

    PubMed

    Silvetti, Massimo; Wiersema, Jan R; Sonuga-Barke, Edmund; Verguts, Tom

    2013-10-01

    Attention Deficit/Hyperactivity Disorder (ADHD) is a pathophysiologically complex and heterogeneous condition with both cognitive and motivational components. We propose a novel computational hypothesis of motivational deficits in ADHD, drawing together recent evidence on the role of anterior cingulate cortex (ACC) and associated mesolimbic dopamine circuits in both reinforcement learning and ADHD. Based on findings of dopamine dysregulation and ACC involvement in ADHD we simulated a lesion in a previously validated computational model of ACC (Reward Value and Prediction Model, RVPM). We explored the effects of the lesion on the processing of reinforcement signals. We tested specific behavioral predictions about the profile of reinforcement-related deficits in ADHD in three experimental contexts; probability tracking task, partial and continuous reward schedules, and immediate versus delayed rewards. In addition, predictions were made at the neurophysiological level. Behavioral and neurophysiological predictions from the RVPM-based lesion-model of motivational dysfunction in ADHD were confirmed by data from previously published studies. RVPM represents a promising model of ADHD reinforcement learning suggesting that ACC dysregulation might play a role in the pathogenesis of motivational deficits in ADHD. However, more behavioral and neurophysiological studies are required to test core predictions of the model. In addition, the interaction with different brain networks underpinning other aspects of ADHD neuropathology (i.e., executive function) needs to be better understood.

  8. 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

  9. Gene expression analysis indicates CB1 receptor upregulation in the hippocampus and neurotoxic effects in the frontal cortex 3 weeks after single-dose MDMA administration in Dark Agouti rats

    PubMed Central

    2013-01-01

    Background 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is a widely used recreational drug known to impair cognitive functions on the long-run. Both hippocampal and frontal cortical regions have well established roles in behavior, memory formation and other cognitive tasks and damage of these regions is associated with altered behavior and cognitive functions, impairments frequently described in heavy MDMA users. The aim of this study was to examine the hippocampus, frontal cortex and dorsal raphe of Dark Agouti rats with gene expression arrays (Illumina RatRef bead arrays) looking for possible mechanisms and new candidates contributing to the effects of a single dose of MDMA (15 mg/kg) 3 weeks earlier. Results The number of differentially expressed genes in the hippocampus, frontal cortex and the dorsal raphe were 481, 155, and 15, respectively. Gene set enrichment analysis of the microarray data revealed reduced expression of 'memory’ and 'cognition’, 'dendrite development’ and 'regulation of synaptic plasticity’ gene sets in the hippocampus, parallel to the upregulation of the CB1 cannabinoid- and Epha4, Epha5, Epha6 ephrin receptors. Downregulated gene sets in the frontal cortex were related to protein synthesis, chromatin organization, transmembrane transport processes, while 'dendrite development’, 'regulation of synaptic plasticity’ and 'positive regulation of synapse assembly’ gene sets were upregulated. Changes in the dorsal raphe region were mild and in most cases not significant. Conclusion The present data raise the possibility of new synapse formation/synaptic reorganization in the frontal cortex three weeks after a single neurotoxic dose of MDMA. In contrast, a prolonged depression of new neurite formation in the hippocampus is suggested by the data, which underlines the particular vulnerability of this brain region after the drug treatment. Finally, our results also suggest the substantial contribution of CB1 receptor and

  10. 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.

  11. The melanin-concentrating hormone1 receptor antagonists, SNAP-7941 and GW3430, enhance social recognition and dialysate levels of acetylcholine in the frontal cortex of rats.

    PubMed

    Millan, Mark J; Gobert, Alain; Panayi, Fany; Rivet, Jean-Michel; Dekeyne, Anne; Brocco, Mauricette; Ortuno, Jean-Claude; Di Cara, Benjamin

    2008-12-01

    Melanin-concentrating hormone (MCH)1 receptors are widely expressed in limbic structures and cortex. Their inactivation is associated with anxiolytic and antidepressive properties but little information is available concerning cognition. This issue was addressed using the selective antagonists, SNAP-7941 and GW3430, in a social recognition paradigm in rats. The muscarinic blocker, scopolamine (1.25 mg/kg s.c.), reduced social recognition, an action dose-dependently blocked by SNAP-7941 and GW3430 (0.63-10.0 and 20.0-80.0 mg/kg i.p., respectively) which did not themselves display amnesic properties. Further, in a protocol where a spontaneous deficit was induced by a prolonged inter-session delay, SNAP-7941 and GW3430 dose-dependently enhanced social recognition. In dialysis studies, SNAP-7941 (0.63-40.0 mg/kg i.p.) and GW3430 (10.0-40.0 mg/kg i.p.) elevated extracellular levels of acetylcholine (ACh) in the frontal cortex (FCX) of freely moving rats. The SNAP-7941 effect was specific, as it did not increase levels of ACh in ventral and dorsal hippocampus: moreover, it did not modify levels of noradrenaline, dopamine, serotonin and glutamate in FCX. Active doses of SNAP-7941 and GW3430 corresponded to doses (2.5-40.0 and 10.0-80.0 mg/kg i.p., respectively) exerting anxiolytic properties in Vogel conflict and ultrasonic vocalization tests, and antidepressant actions in forced swim, isolation-induced aggression and marble-burying procedures. In contrast to SNAP-7941 and GW3430, the benzodiazepine, diazepam, decreased social recognition and dialysate levels of ACh, while the tricyclic, imipramine, reduced social recognition and failed to enhance cholinergic transmission. In conclusion, at anxiolytic and antidepressant doses, SNAP-7941 and GW3430 improve social recognition and elevate extracellular ACh levels in FCX. This profile differentiates MCH1 receptor antagonists from conventional anxiolytic and antidepressant agents.

  12. Reduced gamma frequency in the medial frontal cortex of aged rats during behavior and rest: implications for age-related behavioral slowing

    PubMed Central

    Insel, Nathan; Patron, Lilian A.; Hoang, Lan T.; Nematollahi, Saman; Schimanski, Lesley A.; Lipa, Peter; Barnes, Carol A.

    2012-01-01

    Age-related cognitive and behavioral slowing may be caused by changes in the speed of neural signaling or by changes in the number of signaling steps necessary to achieve a given function. In the mammalian cortex, neural communication is organized by a 30–100 Hz “gamma” oscillation. There is a putative link between the gamma frequency and the speed of processing in a neural network: the dynamics of pyramidal neuron membrane time constants suggest that synaptic integration is framed by the gamma cycle, and pharmacological slowing of gamma also slows reaction times on behavioral tasks. The present experiments identify reductions in a robust 40–70 Hz gamma oscillation in the aged rat medial frontal cortex. The reductions were observed in the form of local field potentials (LFPs), later peaks in fast-spiking neuron autocorrelations, and delays in the spiking of inhibitory neurons following local excitatory signals. Gamma frequency did not vary with movement speed, but rats with slower gamma also moved more slowly. Gamma frequency age differences were not observed in hippocampus. Hippocampal CA1 fast-spiking neurons exhibited inter-spike intervals consistent with a fast (70–100 Hz) gamma frequency, a pattern maintained across theta phases and theta frequencies independent of fluctuations in the neurons’ average firing rates. We propose that an average lengthening of the cortical 15–25 ms gamma cycle is one factor contributing to age-related slowing, and that future attempts to offset cognitive declines will find a target in the response of fast-spiking inhibitory neurons to excitatory inputs. PMID:23152616

  13. Epigenetic regulation of RELN and GAD1 in the frontal cortex (FC) of autism spectrum disorder (ASD) subjects.

    PubMed

    Zhubi, Adrian; Chen, Ying; Guidotti, Alessandro; Grayson, Dennis R

    2017-02-14

    Both Reelin (RELN) and glutamate decarboxylase 67 (GAD1) have been implicated in the pathophysiology of Autism Spectrum Disorders (ASD). We have previously shown that both mRNAs are reduced in the cerebella (CB) of ASD subjects through a mechanism that involves increases in the amounts of MECP2 binding to the corresponding promoters. In the current study, we examined the expression of RELN, GAD1, GAD2, and several other mRNAs implicated in this disorder in the frontal cortices (FC) of ASD and CON subjects. We also focused on the role that epigenetic processes play in the regulation of these genes in ASD brain. Our goal is to better understand the molecular basis for the down-regulation of genes expressed in GABAergic neurons in ASD brains. We measured mRNA levels corresponding to selected GABAergic genes using qRT-PCR in RNA isolated from both ASD and CON groups. We determined the extent of binding of MECP2 and DNMT1 repressor proteins by chromatin immunoprecipitation (ChIP) assays. The amount of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) present in the promoters of the target genes was quantified by methyl DNA immunoprecipitation (MeDIP) and hydroxyl MeDIP (hMeDIP). We detected significant reductions in the mRNAs associated with RELN and GAD1 and significant increases in mRNAs encoding the Ten-eleven Translocation (TET) enzymes 1, 2, and 3. We also detected increased MECP2 and DNMT1 binding to the corresponding promoter regions of GAD1, RELN, and GAD2. Interestingly, there were decreased amounts of 5mC at both promoters and little change in 5hmC content in these same DNA fragments. Our data demonstrate that RELN, GAD1, and several other genes selectively expressed in GABAergic neurons, are down-regulated in post-mortem ASD FC. In addition, we observed increased DNMT1 and MECP2 binding at the corresponding promoters of these genes. The finding of increased MECP2 binding to the RELN, GAD1 and GAD2 promoters, with reduced amounts of 5mC and unchanged

  14. Analysis of kinase gene expression in the frontal cortex of suicide victims: implications of fear and stress.

    PubMed

    Choi, Kwang; Le, Thien; Xing, Guoqiang; Johnson, Luke R; Ursano, Robert J

    2011-01-01

    Suicide is a serious public health issue that results from an interaction between multiple risk factors including individual vulnerabilities to complex feelings of hopelessness, fear, and stress. Although kinase genes have been implicated in fear and stress, including the consolidation and extinction of fearful memories, expression profiles of those genes in the brain of suicide victims are less clear. Using gene expression microarray data from the Online Stanley Genomics Database and a quantitative PCR, we investigated the expression profiles of multiple kinase genes including the calcium calmodulin-dependent kinase (CAMK), the cyclin-dependent kinase, the mitogen-activated protein kinase (MAPK), and the protein kinase C (PKC) in the prefrontal cortex (PFC) of mood disorder patients died with suicide (N = 45) and without suicide (N = 38). We also investigated the expression pattern of the same genes in the PFC of developing humans ranging in age from birth to 49 year (N = 46). The expression levels of CAMK2B, CDK5, MAPK9, and PRKCI were increased in the PFC of suicide victims as compared to non-suicide controls (false discovery rate, FDR-adjusted p < 0.05, fold change >1.1). Those genes also showed changes in expression pattern during the postnatal development (FDR-adjusted p < 0.05). These results suggest that multiple kinase genes undergo age-dependent changes in normal brains as well as pathological changes in suicide brains. These findings may provide an important link to protein kinases known to be important for the development of fear memory, stress associated neural plasticity, and up-regulation in the PFC of suicide victims. More research is needed to better understand the functional role of these kinase genes that may be associated with the pathophysiology of suicide.

  15. Anomalies occurring in lipid profiles and protein distribution in frontal cortex lipid rafts in dementia with Lewy bodies disclose neurochemical traits partially shared by Alzheimer's and Parkinson's diseases.

    PubMed

    Marin, Raquel; Fabelo, Noemí; Martín, Virginia; Garcia-Esparcia, Paula; Ferrer, Isidre; Quinto-Alemany, David; Díaz, Mario

    2017-01-01

    Lipid rafts are highly dynamic membrane microdomains intimately associated with cell signaling. Compelling evidence has demonstrated that alterations in lipid rafts are associated with neurodegenerative diseases such Alzheimer's disease, but at present, whether alterations in lipid raft microdomains occur in other types of dementia such dementia with Lewy bodies (DLB) remains unknown. Our analyses reveal that lipid rafts from DLB exhibit aberrant lipid profiles including low levels of n-3 long-chain polyunsaturated fatty acids (mainly docosahexaenoic acid), plasmalogens and cholesterol, and reduced unsaturation and peroxidability indexes. As a consequence, lipid raft resident proteins holding principal factors of the β-amyloidogenic pathway, including β-amyloid precursor protein, presenilin 1, β-secretase, and PrP, are redistributed between lipid rafts and nonraft domains in DLB frontal cortex. Meta-analysis discloses certain similarities in the altered composition of lipid rafts between DLB and Parkinson's disease which are in line with the spectrum of Lewy body diseases. In addition, redistribution of proteins linked to the β-amyloidogenic pathway in DLB can facilitate generation of β-amyloid, thus providing mechanistic clues to the intriguing convergence of Alzheimer's disease pathology, particularly β-amyloid deposition, in DLB. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Assessment of oxidative stress in hippocampus, cerebellum and frontal cortex in rat pups exposed to lead (Pb) during specific periods of initial brain development.

    PubMed

    Barkur, Rajashekar Rao; Bairy, Laxminarayana Kurady

    2015-04-01

    Epidemiological studies in children have proved that lead (Pb) exposure causes deficits in neural and cognitive functions. The present study assessed the oxidative stress on postnatal day 30, in the hippocampus, cerebellum and frontal cortex of rat pups exposed to Pb during specific periods of early brain development. Five groups of rat pups were investigated, and 0.2% Pb acetate in drinking was the