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Sample records for cortex undergo decreased

  1. Human progenitor cells isolated from the developing cortex undergo decreased neurogenesis and eventual senescence following expansion in vitro

    SciTech Connect

    Wright, Lynda S.; Prowse, Karen R.; Wallace, Kyle; Linskens, Maarten H.K.; Svendsen, Clive N. . E-mail: svendsen@waisman.wisc.edu

    2006-07-01

    Isolation of a true self-renewing stem cell from the human brain would be of great interest as a reliable source of neural tissue. Here, we report that human fetal cortical cells grown in epidermal growth factor expressed low levels of telomerase and telomeres in these cultures shortened over time leading to growth arrest after 30 weeks. Following leukemia inhibitory factor (LIF) supplementation, growth rates and telomerase expression increased. This was best demonstrated following cell cycle synchronization and staining for telomerase using immunocytochemistry. This increase in activity resulted in the maintenance of telomeres at approximately 7 kb for more than 60 weeks in vitro. However, all cultures displayed a lack of oligodendrotye production, decreases in neurogenesis over time and underwent replicative senescence associated with increased expression of p21 before 70 weeks in vitro. Thus, under our culture conditions, these cells are not stable, multipotent, telomerase expressing self-renewing stem cells. They may be more accurately described as human neural progenitor cells (hNPC) with limited lifespan and bi-potent potential (neurons/astrocytes). Interestingly, hNPC follow a course of proliferation, neuronal production and growth arrest similar to that seen during expansion and development of the human cortex, thus providing a possible model neural system. Furthermore, due to their high expansion potential and lack of tumorogenicity, these cells remain a unique and safe source of tissue for clinical transplantation.

  2. Increased Visual Stimulation Systematically Decreases Activity in Lateral Intermediate Cortex.

    PubMed

    Nasr, Shahin; Stemmann, Heiko; Vanduffel, Wim; Tootell, Roger B H

    2015-10-01

    Previous studies have attributed multiple diverse roles to the posterior superior temporal cortex (STC), both visually driven and cognitive, including part of the default mode network (DMN). Here, we demonstrate a unifying property across this multimodal region. Specifically, the lateral intermediate (LIM) portion of STC showed an unexpected feature: a progressively decreasing fMRI response to increases in visual stimulus size (or number). Such responses are reversed in sign, relative to well-known responses in classic occipital temporal visual cortex. In LIM, this "reversed" size function was present across multiple object categories and retinotopic eccentricities. Moreover, we found a significant interaction between the LIM size function and the distribution of subjects' attention. These findings suggest that LIM serves as a part of the DMN. Further analysis of functional connectivity, plus a meta-analysis of previous fMRI results, suggests that LIM is a heterogeneous area including different subdivisions. Surprisingly, analogous fMRI tests in macaque monkeys did not reveal a clear homolog of LIM. This interspecies discrepancy supports the idea that self-referential thinking and theory of mind are more prominent in humans, compared with monkeys.

  3. 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.

  4. 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.

  5. Correlations Decrease with Propagation of Spiking Activity in the Mouse Barrel Cortex

    PubMed Central

    Ranganathan, Gayathri Nattar; Koester, Helmut Joachim

    2011-01-01

    Propagation of suprathreshold spiking activity through neuronal populations is important for the function of the central nervous system. Neural correlations have an impact on cortical function particularly on the signaling of information and propagation of spiking activity. Therefore we measured the change in correlations as suprathreshold spiking activity propagated between recurrent neuronal networks of the mammalian cerebral cortex. Using optical methods we recorded spiking activity from large samples of neurons from two neural populations simultaneously. The results indicate that correlations decreased as spiking activity propagated from layer 4 to layer 2/3 in the rodent barrel cortex. PMID:21629764

  6. The Number of Chandelier and Basket Cells Are Differentially Decreased in Prefrontal Cortex in Autism.

    PubMed

    Ariza, Jeanelle; Rogers, Haille; Hashemi, Ezzat; Noctor, Stephen C; Martínez-Cerdeño, Verónica

    2016-11-24

    An interneuron alteration has been proposed as a source for the modified balance of excitation / inhibition in the cerebral cortex in autism. We previously demonstrated a decreased number of parvalbumin (PV)-expressing interneurons in prefrontal cortex in autism. PV-expressing interneurons include chandelier (Ch) and basket (Bsk) cells. We asked whether the decreased PV+ interneurons affected both Ch cells and Bsk cells in autism. The lack of single markers to specifically label Ch cells or Bsk cells presented an obstacle for addressing this question. We devised a method to discern between PV-Ch and PV-Bsk cells based on the differential expression of Vicia villosa lectin (VVA). VVA binds to N-acetylgalactosamine, that is present in the perineuronal net surrounding some cell types where it plays a role in intercellular communication. N-acetylgalactosamine is present in the perineuronal net surrounding Bsk but not Ch cells. We found that the number of Ch cells is consistently decreased in the prefrontal cortex of autistic (n = 10) when compared with control (n = 10) cases, while the number of Bsk cells is not as severely affected. This finding expand our understanding of GABAergic system functioning in the human cerebral cortex in autism, which will impact translational research directed towards providing better treatment paradigms for individuals with autism.

  7. Decrease in doublecortin expression without neuronal cell death in rat retrosplenial cortex after stress exposure.

    PubMed

    Kutsuna, Nobuo; Suma, Takeshi; Takada, Yoshiyuki; Yamashita, Akiko; Oshima, Hideki; Sakatani, Kaoru; Yamamoto, Takamitsu; Katayama, Yoichi

    2012-03-07

    Exposure to acute stress by forced swim impairs spatial learning and memory in rats. The retrosplenial cortex plays an important role in spatial learning and memory. A cell population that expresses immature neuronal markers, including doublecortin (DCX), plays a key role in plasticity of the adult brain through formation of new neurons. Here, we aimed to determine whether rats exposed to acute stress showed changes in DCX expression in retrosplenial cortex cells. Twelve male Sprague-Dawley rats were used. Six were subjected to acute stress by forced swim (group S), and the remaining six served as controls (group C). Immunohistochemical staining was performed for DCX, neuron-specific nuclear protein, parvalbumin, calbindin, calretinin, and somatostatin. Newly generated cells were immunohistochemically detected by daily administration of 5-bromo-2'-deoxyuridine for 1 week. Fluoro-Jade B staining was performed to detect cell death. Group S showed lower number of DCX-expressing cells than group C (P<0.001). The proportion of DCX-expressing cells showing neuron-specific nuclear protein co-localization (24% in group S; 27% in group C) or parvalbumin co-localization (65% in group S; 61% in group C) remained unchanged after acute stress exposure. Neither 5-bromo-2'-deoxyuridine-positive nor Fluoro-Jade B-positive cells were found in the retrosplenial cortex of groups S and C. DCX-expressing cells in the retrosplenial cortex decreases markedly without cell death after acute stress exposure. Neuronal differentiation of these cells toward gamma aminobutyric acidergic interneurons appears to be unaltered. The decrease in DCX expression may reduce plasticity potential within the retrosplenial cortex and attenuate spatial learning and memory function.

  8. Single bolus of intravenous ketamine for anesthetic induction decreases oculocardiac reflex in children undergoing strabismus surgery.

    PubMed

    Choi, S H; Lee, S J; Kim, S H; Kim, J H; Kwon, H H; Shin, Y S; Lee, K Y

    2007-07-01

    Oculocardiac reflex (OCR) is a major complication of pediatric strabismus surgery. The aim of the present study was to determine whether a single bolus of intravenous (i.v.) ketamine for anesthetic induction can decrease OCR in children undergoing strabismus surgery. One hundred and twenty healthy children undergoing strabismus surgery were allocated to three groups using double-blind randomization. Anesthesia was induced with propofol 3 mg/kg in Group P, ketamine 1 mg/kg in Group K1, or ketamine 2 mg/kg in Group K2. Anesthesia was maintained with 3% sevoflurane in 50% N(2)O/O(2) in all patients. The baseline heart rate was obtained 30 s prior to the first traction of the extraocular muscle (EOM). OCR was defined as a development of arrhythmia or a decrease of more than 20% of the baseline heart rate during EOM traction. The incidence of OCR was significantly lower in the ketamine groups (4/40 and 1/40 in Group K1 and K2, respectively) compared with the propofol group (14/40). A single bolus of i.v. ketamine 1 or 2 mg/kg for anesthetic induction results in a lower incidence of OCR than propofol when combined with sevoflurane for maintenance in children undergoing strabismus surgery.

  9. Impaired synaptic plasticity in the prefrontal cortex of mice with developmentally decreased number of interneurons.

    PubMed

    Konstantoudaki, X; Chalkiadaki, K; Tivodar, S; Karagogeos, D; Sidiropoulou, K

    2016-05-13

    Interneurons are inhibitory neurons, which protect neural tissue from excessive excitation. They are interconnected with glutamatergic pyramidal neurons in the cerebral cortex and regulate their function. Particularly in the prefrontal cortex (PFC), interneurons have been strongly implicated in regulating pathological states which display deficits in the PFC. The aim of this study is to investigate the adaptations in the adult glutamatergic system, when defects in interneuron development do not allow adequate numbers of interneurons to reach the cerebral cortex. To this end, we used a mouse model that displays ~50% fewer cortical interneurons due to the Rac1 protein loss from Nkx2.1/Cre expressing cells (Rac1 conditional knockout (cKO) mice), to examine how the developmental loss of interneurons may affect basal synaptic transmission, synaptic plasticity and neuronal morphology in the adult PFC. Despite the decrease in the number of interneurons, basal synaptic transmission, as examined by recording field excitatory postsynaptic potentials (fEPSPs) from layer II networks, is not altered in the PFC of Rac1 cKO mice. However, there is decreased paired-pulse ratio (PPR) and decreased long-term potentiation (LTP), in response to tetanic stimulation, in the layer II PFC synapses of Rac1 cKO mice. Furthermore, expression of N-methyl-d-aspartate (NMDA) subunits is decreased and dendritic morphology is altered, changes that could underlie the decrease in LTP in the Rac1 cKO mice. Finally, we find that treating Rac1 cKO mice with diazepam in early postnatal life can reverse changes in dendritic morphology observed in non-treated Rac1 cKO mice. Therefore, our data show that disruption in GABAergic inhibition alters glutamatergic function in the adult PFC, an effect that could be reversed by enhancement of GABAergic function during an early postnatal period.

  10. Gray matter decrease of the anterior cingulate cortex in anorexia nervosa.

    PubMed

    Mühlau, Mark; Gaser, Christian; Ilg, Rüdiger; Conrad, Bastian; Leibl, Carl; Cebulla, Marian H; Backmund, Herbert; Gerlinghoff, Monika; Lommer, Peter; Schnebel, Andreas; Wohlschläger, Afra M; Zimmer, Claus; Nunnemann, Sabine

    2007-12-01

    The brain regions that are critically involved in the pathophysiology of anorexia nervosa have not been clearly elucidated. Moreover, decrease in cerebral tissue during extreme malnutrition has been demonstrated repeatedly in anorexia nervosa, but data regarding the reversibility of this cerebral tissue decrease are conflicting. The authors examined region-specific gray matter changes and global cerebral volumes in recovered patients with anorexia nervosa. High-resolution, T1-weighted magnetic resonance imaging (MRI) and voxel-based morphometry were performed in 22 recovered women with anorexia nervosa and in 37 healthy comparison women. Recovery was defined as a body mass index above 17.0 kg/m(2) and regular menses for at least 6 months. The global volumes of gray matter (but not white matter) were decreased in patients with anorexia nervosa by approximately 1%. Analyses of region-specific gray matter changes revealed a gray matter decrease bilaterally in the anterior cingulate cortex of approximately 5%, which remained significant after correction for global effects. This gray matter decrease correlated significantly with the lowest body mass index of lifetime but not with other clinical variables. In anorexia nervosa, part of the global gray matter loss persists over the long run. Region-specific gray matter loss in the anterior cingulate cortex is directly related to the severity of anorexia nervosa, indicating an important role of this area in the pathophysiology of the disorder. Further research is warranted to determine the cause, specificity, and functional consequences of this structural brain change in anorexia nervosa.

  11. Prenatal Protein Malnutrition Decreases KCNJ3 and 2DG Activity in Rat Prefrontal Cortex

    PubMed Central

    Amaral, A.C.; Jakovcevski, M.; McGaughy, J.A.; Calderwood, S.K.; Mokler, D.J.; Rushmore, R.J.; Galler, J.R.; Akbarian, S.A.; Rosene, D.L.

    2014-01-01

    Prenatal protein malnutrition (PPM) in rats causes enduring changes in brain and behavior including increased cognitive rigidity and decreased inhibitory control. A preliminary gene microarray screen of PPM rat prefrontal cortex (PFC) identified alterations in KCNJ3 (GIRK1/Kir3.1), a gene important for regulating neuronal excitability. Follow-up with polymerase chain reaction and Western blot showed decreased KCNJ3 expression in PFC, but not hippocampus or brainstem. To verify localization of the effect to the PFC, baseline regional brain activity was assessed with 14C-2-deoxyglucose. Results showed decreased activation in PFC but not hippocampus. Together these findings point to the unique vulnerability of the PFC to the nutritional insult during early brain development, with enduring effects in adulthood on KCNJ3 expression and baseline metabolic activity. PMID:25446346

  12. Prenatal protein malnutrition decreases KCNJ3 and 2DG activity in rat prefrontal cortex.

    PubMed

    Amaral, A C; Jakovcevski, M; McGaughy, J A; Calderwood, S K; Mokler, D J; Rushmore, R J; Galler, J R; Akbarian, S A; Rosene, D L

    2015-02-12

    Prenatal protein malnutrition (PPM) in rats causes enduring changes in brain and behavior including increased cognitive rigidity and decreased inhibitory control. A preliminary gene microarray screen of PPM rat prefrontal cortex (PFC) identified alterations in KCNJ3 (GIRK1/Kir3.1), a gene important for regulating neuronal excitability. Follow-up with polymerase chain reaction and Western blot showed decreased KCNJ3 expression in the PFC, but not hippocampus or brainstem. To verify localization of the effect to the PFC, baseline regional brain activity was assessed with (14)C-2-deoxyglucose. Results showed decreased activation in the PFC but not hippocampus. Together these findings point to the unique vulnerability of the PFC to the nutritional insult during early brain development, with enduring effects in adulthood on KCNJ3 expression and baseline metabolic activity.

  13. Capturing Pain in the Cortex during General Anesthesia: Near Infrared Spectroscopy Measures in Patients Undergoing Catheter Ablation of Arrhythmias

    PubMed Central

    Yücel, Meryem A.; Steele, Sarah C.; Alexander, Mark E.; Boas, David A.; Borsook, David; Becerra, Lino

    2016-01-01

    The predictability of pain makes surgery an ideal model for the study of pain and the development of strategies for analgesia and reduction of perioperative pain. As functional near-infrared spectroscopy reproduces the known functional magnetic resonance imaging activations in response to a painful stimulus, we evaluated the feasibility of functional near-infrared spectroscopy to measure cortical responses to noxious stimulation during general anesthesia. A multichannel continuous wave near-infrared imager was used to measure somatosensory and frontal cortical activation in patients undergoing catheter ablation of arrhythmias under general anesthesia. Anesthetic technique was standardized and intraoperative NIRS signals recorded continuously with markers placed in the data set for the timing and duration of each cardiac ablation event. Frontal cortical signals only were suitable for analysis in five of eight patients studied (mean age 14 ± 1 years, weight 66.7 ± 17.6 kg, 2 males). Thirty ablative lesions were recorded for the five patients. Radiofrequency or cryoablation was temporally associated with a hemodynamic response function in the frontal cortex characterized by a significant decrease in oxyhemoglobin concentration (paired t-test, p<0.05) with the nadir occurring in the period 4 to 6 seconds after application of the ablative lesion. Cortical signals produced by catheter ablation of arrhythmias in patients under general anesthesia mirrored those seen with noxious stimulation in awake, healthy volunteers, during sedation for colonoscopy, and functional Magnetic Resonance Imaging activations in response to pain. This study demonstrates the feasibility and potential utility of functional near-infrared spectroscopy as an objective measure of cortical activation under general anesthesia. PMID:27415436

  14. Decreased synaptic and mitochondrial density in the postmortem anterior cingulate cortex in schizophrenia

    PubMed Central

    Roberts, RC; Barksdale, KA; Roche, JK; Lahti, AC

    2015-01-01

    Schizophrenia (SZ) is a mental illness characterized by psychosis, negative symptoms, and cognitive deficits. The anterior cingulate cortex (ACC), a structurally and functionally diverse region, is one of several brain regions that is abnormal in SZ. The present study compared synaptic organization and mitochondrial number and morphology in postmortem ACC in SZ versus normal control (NC). Total synaptic density in the combined ACC was decreased in SZ, to 72% of normal controls (NCs), due to selective decreases in axospinous synapses, both asymmetric (excitatory) and symmetric (inhibitory). These changes were present in layers 3 and 5/6. The density of mitochondria in all axon terminals combined in SZ was decreased to 64% of NC. In layer 3, mitochondrial density was decreased only in terminals forming asymmetric synapses with spines, while in layers 5/6 mitochondrial density was decreased in terminals forming symmetric synapses with spines and dendrites. The proportion of terminals making symmetric synapses that contained mitochondria was significantly lower in SZ than in NCs, especially for symmetric axospinous synapses. The number of mitochondria per neuronal somata was decreased in the ACC in SZ compared to NCs; this finding was present in layers 5-6. The size of mitochondria in neuronal somata and throughout the neuropil was similar in SZ and NCs. Our results, though preliminary, are well supported by the literature, and support an anatomical substrate for some of the altered executive functions found in SZ. PMID:26210550

  15. Neurotensin decreases high affinity [3H]-ouabain binding to cerebral cortex membranes.

    PubMed

    Rosin, Carina; Ordieres, María Graciela López; Arnaiz, Georgina Rodríguez de Lores

    2011-12-10

    Previous work from this laboratory showed the ability of neurotensin to inhibit synaptosomal membrane Na(+), K(+)-ATPase activity, the effect being blocked by SR 48692, a non-peptidic antagonist for high affinity neurotensin receptor (NTS1) [López Ordieres and Rodríguez de Lores Arnaiz 2000; 2001]. To further study neurotensin interaction with Na(+), K(+)-ATPase, peptide effect on high affinity [(3)H]-ouabain binding was studied in cerebral cortex membranes. It was observed that neurotensin modified binding in a dose-dependent manner, leading to 80% decrease with 1 × 10(-4)M concentration. On the other hand, the single addition of 1 × 10(-6)M, 1 × 10(-5)M and 1 × 10(-4)M SR 48692 (Sanofi-Aventis, U.S., Inc.) decreased [(3)H]-ouabain binding (in %) to 87 ± 16; 74 ± 16 and 34 ± 17, respectively. Simultaneous addition of neurotensin and SR 48692 led to additive or synergic effects. Partial NTS2 agonist levocabastine inhibited [(3)H]-ouabain binding likewise. Saturation assays followed by Scatchard analyses showed that neurotensin increased K(d) value whereas failed to modify B(max) value, indicating a competitive type interaction of the peptide at Na(+), K(+)-ATPase ouabain site. At variance, SR 48692 decreased B(max) value whereas it did not modify K(d) value. [(3)H]-ouabain binding was also studied in cerebral cortex membranes obtained from rats injected i. p. 30 min earlier with 100 μg and 250 μg/kg SR 48692. It was observed that the 250 μg/kg SR 48692 dose led to 19% decrease in basal [(3)H]-ouabain binding. After SR 48692 treatments, addition of 1 × 10(-6)M led to additive or synergic effect. Results suggested that [(3)H]-ouabain binding inhibition by neurotensin hardly involves NTS1 receptor.

  16. 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.

  17. Decreased parvalbumin immunoreactivity in the cortex and striatum of mice lacking the CB1 receptor

    PubMed Central

    Fitzgerald, Megan L.; Lupica, Carl R.; Pickel, Virginia M.

    2011-01-01

    Cortical and striatal regions of the brain contain high levels of the cannabinoid-1 (CB1) receptor, the central neuronal mediator of activity-dependent synaptic plasticity evoked by endocannabinoids. The expression levels of parvalbumin, a calcium-binding protein found in fast-spiking interneurons of both regions, may be controlled in part by synaptic activity during critical periods of development. However, there is presently no evidence that CB1 receptor expression affects parvalbumin levels in either cortical or striatal interneurons. To assess this possibility, we examined parvalbumin immunoreactivity in the dorsolateral striatum, primary motor cortex (M1), and prefrontal cortex (PFC) of CB1 knockout and wild-type C57/BL6 mice. Quantitative densitometry showed a significant decrease in parvalbumin immunoreactivity within individual neurons in each of these regions of CB1 knockout mice relative to the controls. A significantly lower density (number of cells per unit area) of parvalbumin-labeled neurons was observed in the striatum, but not the cortical regions of CB1 knockout mice. These findings suggest that CB1 receptor deletion may elicit a compensatory mechanism for network homeostasis affecting parvalbumin-containing cortical and striatal interneurons. PMID:21445945

  18. Dopaminergic reward signals selectively decrease fMRI activity in primate visual cortex

    PubMed Central

    Arsenault, J.T.; Nelissen, K.; Jarraya, B.; Vanduffel, W.

    2013-01-01

    Summary Stimulus-reward coupling without attention can induce highly specific perceptual learning effects, suggesting that rewards trigger selective plasticity within visual cortex. Additionally, dopamine-releasing events - temporally-surrounding stimulus-reward associations - selectively enhance memory. These forms of plasticity may be evoked by selective modulation of stimulus representations during dopamine-inducing events. However, it remains to be shown whether dopaminergic signals can selectively modulate visual cortical activity. We measured fMRI activity in monkey visual cortex during reward-only trials apart from intermixed cue-reward trials. Rewards without visual stimulation selectively decreased fMRI activity within the cue representations that had been paired with rewards during other trials. Behavioral tests indicated that these same uncued reward trials strengthened cue-reward associations. Furthermore, such spatially-specific activity modulations depended on prediction error, as shown by manipulations of reward magnitude, cue-reward probability, cue-reward familiarity, and dopamine signaling. This cue-selective negative reward signal offers a mechanism for selectively gating sensory cortical plasticity. PMID:23522051

  19. Decreased GABAA receptors and benzodiazepine binding sites in the anterior cingulate cortex in autism

    PubMed Central

    Oblak, A.; Gibbs, T.T.; Blatt, G.J.

    2009-01-01

    The anterior cingulate cortex (ACC; BA 24) via its extensive limbic and high order association cortical connectivity to prefrontal cortex is a key part of an important circuitry participating in executive function, affect, and socio-emotional behavior. Multiple lines of evidence, including genetic and imaging studies, suggest that the ACC and GABA system may be affected in autism. The benzodiazepine binding site on the GABAA receptor complex is an important target for pharmacotherapy and has important clinical implications. The present multiple-concentration ligand-binding study utilized 3H-muscimol and 3H-flunitrazepam to determine the number (Bmax), binding affinity (Kd), and distribution of GABAA receptors and benzodiazepine binding sites, respectively, in the ACC in adult autistic and control cases. Compared to controls, the autistic group had significant decreases in the mean density of GABAA receptors in the supragranular (46.8%) and infragranular (20.2%) layers of the ACC and in the density of benzodiazepine binding sites in the supragranular (28.9%) and infragranular (16.4 %) lamina. In addition, a trend for a decrease in for the density of benzodiazepine sites was found in the infragranular layers (17.1%) in the autism group. These findings suggest that in the autistic group this downregulation of both benzodiazepine sites and GABAA receptors in the ACC may be the result of increased GABA innervation and/or release disturbing the delicate excitation/inhibition balance of principal neurons as well as their output to key limbic cortical targets. Such disturbances likely underlie the core alterations in socio-emotional behaviors in autism. PMID:19650112

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

    PubMed

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

    2017-09-01

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

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

    PubMed

    McCarthy, Deirdre M; Bhide, Pradeep G

    2012-01-01

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

  2. Knife cuts of entorhinal cortex: effects on development of amygdaloid kindling and seizure-induced decrease of muscarinic cholinergic receptors

    SciTech Connect

    Savage, D.D.; Rigsbee, L.C.; McNamara, J.O.

    1985-02-01

    This report examines the effect of transection of the entorhinal hippocampal projection on amygdaloid kindling. We found that: bilateral knife cuts of entorhinal cortex but not of dorsal neocortex antagonize the development of amygdaloid kindling; and bilateral knife cuts of entorhinal cortex eliminate the seizure-induced decrease in number of muscarinic receptors of dentate granule cells. We suggest the following interpretations of these data: the hippocampal formation circuitry facilitates the development of amygdaloid kindling; and the decline of muscarinic receptors after kindled seizures is due to excessive activation of granule cells by axons from entorhinal cortex, a noncholinergic afferent.

  3. Cannabinoids Occlude the HIV-1 Tat-Induced Decrease in GABAergic Neurotransmission in Prefrontal Cortex Slices.

    PubMed

    Xu, Changqing; Hermes, Douglas J; Mackie, Ken; Lichtman, Aron H; Ignatowska-Jankowska, Bogna M; Fitting, Sylvia

    2016-06-01

    In the era of combined antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) is now considered a chronic disease that specifically targets the brain and causes HIV-1-associated neurocognitive disorders (HAND). Endocannabinoids exhibit neuroprotective and anti-inflammatory properties in several central nervous system (CNS) disease models, but their effects in HAND are poorly understood. To address this issue, whole-cell recordings were performed on young (14-24 day old) C57BL/6J mice. We investigated the actions of the synthetic cannabinoid WIN55,212-2 (1 μM) and the endocannabinoid N-arachidonoyl ethanolamine (anandamide; AEA, 1 μM) in the presence of HIV-1 Tat on GABAergic neurotransmission in mouse prefrontal cortex (PFC) slices. We found a Tat concentration-dependent (5-50 nM) decrease in the frequency and amplitude of miniature inhibitory postsynaptic currents (mIPSCs). The cannabinoid 1 receptor (CB1R) antagonist rimonabant (1 μM) and zero extracellular calcium prevented the significant Tat-induced decrease in mIPSCs. Further, bath-applied WIN55,212-2 or AEA by itself, significantly decreased the frequency, but not amplitude of mIPSCs and/or spontaneous IPSCs (sIPSCs), and occluded a further downregulation of IPSCs by Tat. Pretreatment with rimonabant but not the CB2R antagonist AM630 (1 μM) prevented the WIN55,212-2- and AEA-induced decrease in IPSCs frequency without any further Tat effect. Results indicated a Tat-induced decrease in GABAergic neurotransmission, which was occluded by cannabinoids via a CB1R-related mechanism. Understanding the relationship between Tat toxicity and endocannabinoid signaling has the potential to identify novel therapeutic interventions to benefit individuals suffering from HAND and other cognitive impairments.

  4. Cannabinoids occlude the HIV-1 Tat-induced decrease in GABAergic neurotransmission in prefrontal cortex slices

    PubMed Central

    Xu, Changqing; Hermes, Douglas J; Mackie, Ken; Lichtman, Aron H; Ignatowska-Jankowska, Bogna M; Fitting, Sylvia

    2016-01-01

    In the era of combined antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) is now considered a chronic disease that specifically targets the brain and causes HIV-1-associated neurocognitive disorders (HAND). Endocannabinoids exhibit neuroprotective and anti-inflammatory properties in several central nervous system (CNS) disease models, but their effects in HAND are poorly understood. To address this issue, whole-cell recordings were performed on young (14 – 21 day old) C57BL/6J mice. We investigated the actions of the synthetic cannabinoid WIN55,212-2 (1 μM) and the endocannabinoid N-arachidonoyl ethanolamine (anandamide; AEA, 1 μM) in the presence of HIV-1 Tat on GABAergic neurotransmission in mouse prefrontal cortex (PFC) slices. We found a Tat concentration dependent (5 – 50 nM) decrease in the frequency and amplitude of miniature inhibitory postsynaptic currents (mIPSCs). The cannabinoid 1 receptor (CB1R) antagonist rimonabant (1 μM) and zero extracellular calcium prevented the significant Tat-induced decrease in mIPSCs. Further, bath-applied WIN55,212-2 or AEA by itself, significantly decreased the frequency, but not amplitude of mIPSCs and/or spontaneous IPSCs (sIPSCs), and occluded a further down-regulation of IPSCs by Tat. Pretreatment with rimonabant but not the CB2R antagonist AM630 (1 μM) prevented the WIN55,212-2- and AEA-induced decrease in IPSCs frequency without any further Tat effect. Results indicated a Tat-induced decrease in GABAergic neurotransmission, which was occluded by cannabinoids via a CB1R-related mechanism. Understanding the relationship between Tat toxicity and endocannabinoid signaling has the potential to identify novel therapeutic interventions to benefit individuals suffering from HAND and other cognitive impairments. PMID:26993829

  5. Exercise-induced decrease in insular cortex rCBF during postexercise hypotension.

    PubMed

    Lamb, Kala; Gallagher, Kevin; McColl, Roderick; Mathews, Dana; Querry, Ross; Williamson, Jon W

    2007-04-01

    The insular cortex (IC), a region of the brain involved in blood pressure (BP) modulation, shows decreases in regional cerebral blood flow (rCBF) during postexercise hypotension (PEH). To determine whether changes in IC neural activity were caused by prior exercise or by changes in BP, this investigation compared patterns of rCBF during periods of hypotension, which was induced by prior exercise (i.e., PEH) and sodium nitroprusside (SNP) infusion and a cold pressor (CP), to restore BP. Ten subjects were studied on three different days with randomly assigned conditions: i) resting baseline; ii) PEH; and iii) SNP-induced hypotension (matched to the PEH BP decrease). Data were collected for heart rate (HR) and mean BP, and rCBF was assessed using single-photon emission computed tomography (SPECT) as an index of brain activation. Using ANOVA across conditions, there were differences (P<0.05; mean +/- SD) from baseline during PEH for HR (+12 +/- 3 bpm) and mean BP (-8 +/- 2 mm Hg) and during SNP-induced hypotension (HR = +15 +/- 4 bpm; MBP = -9 +/- 2 mm Hg), with no differences between PEH and SNP. After exercise, there were decreases (P<0.05) in the leg sensorimotor area, anterior cingulate, and the right and left inferior thalamus, right inferior insula, and left anterior insular regions. During SNP-induced hypotension, there were significant increases in the right and left inferior thalamus and the right and left inferior anterior IC. CP during PEH increased BP and IC activity. Data show that reductions in IC neural activity are not caused by acute BP decreases. Findings suggest that exercise can lead to a temporary decrease in IC neural activity, which may be a significant neural factor contributing to PEH.

  6. Decreased Cingulate Cortex activation during cognitive control processing in bipolar disorder.

    PubMed

    Gruber, Staci A; Dahlgren, M Kathryn; Sagar, Kelly A; Gonenc, Atilla; Norris, Lesley; Cohen, Bruce M; Ongur, Dost; Lewandowski, Kathryn E

    2017-04-15

    Cognitive deficits are well-documented in patients with bipolar disorder (BPD) and may impact the efficacy of psychotherapy. Cognitive control, a form of executive functioning, is often used therapeutically to shift patients' thoughts and behaviors from automatic, maladaptive responses to adaptive coping strategies. This study examined cognitive control processing in patients with BPD using the Multi-Source Interference Task (MSIT). Twenty-nine patients diagnosed with BPD and 21 healthy control (HC) subjects completed the MSIT with concurrent functional magnetic resonance imaging (fMRI). Patients with BPD generally performed worse on the MSIT relative to HC participants; the BPD group had significantly lower performance accuracy and made more omission errors. Further, fMRI analyses revealed differential patterns of activation between the groups during the MSIT. Region of interest (ROI) analyses revealed that relative to HC participants, patients with BPD activated significantly fewer voxels within the cingulate cortex (CC) and more voxels within prefrontal cortex (PFC), although the PFC findings did not survive more stringent significance thresholds. Patients and HCs were not matched for age, sex, and premorbid verbal IQ, however, these variables were controlled for statistically. Medication usage in the BPD group may have possibly impacted the results. Given a priori hypotheses, ROI analyses were utilized. Decreased CC activation and increased PFC activation may be associated with impaired cognitive control, demonstrated by BPD patients when completing the MSIT. Identifying the neural mechanisms which underlie key cognitive abnormalities in BPD may aid in clarifying the pathophysiology of this disorder and inform selection of potential targets for cognition remediation in BPD. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  7. DCX-expressing neurons decrease in the retrosplenial cortex after global brain ischemia.

    PubMed

    Kutsuna, Nobuo; Murata, Yoshihiro; Eriguchi, Takashi; Takada, Yoshiyuki; Oshima, Hideki; Sakatani, Kaoru; Katayama, Yoichi

    2013-01-01

    Many studies have demonstrated cognitive function disorders including space learning disorders after global brain ischemia (GBI). Previous research on space perception and learning has indicated that the retrosplenial cortex (RS) is strongly involved. We performed immunostaining with doublecortin (DCX) for neurons with plasticity potential in the RS and investigated the neuronal numbers to assess the changes of plasticity in the RS following GBI. We employed male Sprague-Dawley rats and carried out bilateral carotid arterial occlusion for 10 min as a GBI model (control, n = 5; GBI model, n = 5). We counted the right and left hemispheres separately on two serial sections, for a total of four regions per animal to examine the differences in expression related to GBI. Additionally, we performed Fluoro-Jade B (FJB) staining to investigate the cause of any DCX-expressing neuron decrease. The total number of DCX-expressing neurons was 1,652 and 912 in the controls and GBI model, respectively. The mean number of DCX-expressing neurons per unit area was significantly lower in the GBI model than in the controls. FJB positive neurons were not found in the RS, while many were present in the -hippocampus CA1 after GBI. The decrease of DCX-expressing neurons in the RS indicated a plasticity decrease following GBI. The lack of FJB positive neurons in the RS after GBI suggested that the decrease of DCX-expressing neurons in the RS was not due to neuronal cell death in contrast to the hippocampus CA1, while the FJB positive neurons in the hippocampus indicated a delayed neuronal cell death as observed in many previous studies.

  8. Ventromedial Prefrontal Cortex Damage Is Associated with Decreased Ventral Striatum Volume and Response to Reward

    PubMed Central

    Pujara, Maia S.; Philippi, Carissa L.; Motzkin, Julian C.; Baskaya, Mustafa K.

    2016-01-01

    The ventral striatum and ventromedial prefrontal cortex (vmPFC) are two central nodes of the “reward circuit” of the brain. Human neuroimaging studies have demonstrated coincident activation and functional connectivity between these brain regions, and animal studies have demonstrated that the vmPFC modulates ventral striatum activity. However, there have been no comparable data in humans to address whether the vmPFC may be critical for the reward-related response properties of the ventral striatum. In this study, we used fMRI in five neurosurgical patients with focal vmPFC lesions to test the hypothesis that the vmPFC is necessary for enhancing ventral striatum responses to the anticipation of reward. In support of this hypothesis, we found that, compared with age- and gender-matched neurologically healthy subjects, the vmPFC-lesioned patients had reduced ventral striatal activity during the anticipation of reward. Furthermore, we observed that the vmPFC-lesioned patients had decreased volumes of the accumbens subregion of the ventral striatum. Together, these functional and structural neuroimaging data provide novel evidence for a critical role for the vmPFC in contributing to reward-related activity of the ventral striatum. These results offer new insight into the functional and structural interactions between key components of the brain circuitry underlying human affective function and decision-making. SIGNIFICANCE STATEMENT Maladaptive decision-making is a common problem across multiple mental health disorders. Developing new pathophysiologically based strategies for diagnosis and treatment thus requires a better understanding of the brain circuits responsible for adaptive decision-making and related psychological subprocesses (e.g., reward valuation, anticipation, and motivation). Animal studies provide evidence that these functions are mediated through direct interactions between two key nodes of a posited “reward circuit,” the ventral striatum and

  9. Subjective feeling of psychological fatigue is related to decreased reactivity in ventrolateral prefrontal cortex.

    PubMed

    Suda, Masashi; Fukuda, Masato; Sato, Toshimasa; Iwata, Shinya; Song, Mingqiao; Kameyama, Masaki; Mikuni, Masahiko

    2009-02-03

    The purpose of this study is to examine the relationship between subjective fatigue and brain function. Twenty-three healthy young volunteers participated in this study. Relationships were investigated between subjective fatigue assessed using visual-analogue scale (VAS) score and sleep duration, and cerebral cortex reactivity during a verbal fluency task by 52-channel near-infrared spectroscopy (NIRS). The VAS score negatively correlated with oxygenated hemoglobin concentration ([oxy-Hb]) increases in the bilateral channels over the regions from the ventrolateral part of the frontal lobe to the upper part of the temporal lobe during the verbal fluency task. Sleep duration in the previous night positively correlated with [oxy-Hb] increases in the bilateral channels over the dorsolateral prefrontal lobe also during the verbal fluency task. No significant correlations between the VAS score and sleep duration in the previous night with [oxy-Hb] increases were found during a control task, the left-finger-tapping task. The subjective feeling of psychological fatigue is related to decreased reactivities in the lateral frontal and superior temporal cortices and is unrelated to sleep duration in the previous night, which is reflected in the reactivity in the dorsolateral prefrontal cortices. These results suggest that transient hypofunction and persistent dysfunction in the lateral prefrontal and temporal lobes are among the brain substrates of fatigue. These also demonstrate the advantage of NIRS for investigating brain function during subjective phenomena such as fatigue because it enables examination in a natural setting.

  10. Toluene decreases Purkinje cell output by enhancing inhibitory synaptic transmission in the cerebellar cortex.

    PubMed

    Gmaz, Jimmie M; McKay, Bruce E

    2014-02-07

    Toluene belongs to a class of psychoactive drugs known as inhalants. Found in common household products such as adhesives, paint products, and aerosols, toluene is inhaled for its intoxicating and euphoric properties. Additionally, exposure to toluene disrupts motor behaviors in a manner consistent with impairments to cerebellar function. Previous work has suggested a role of GABA in mediating toluene's neurobehavioral effects, but how this manifests in the cerebellar cortex is not yet understood. In the present study, we examined the effects of toluene on cerebellar Purkinje cell action potential output and inhibitory synaptic transmission onto Purkinje cells using patch clamp electrophysiology in acute rat cerebellar slices. Toluene (1mM) reduced the frequency of Purkinje cell action potential output without affecting input resistance. Furthermore, toluene dose-dependently enhanced inhibitory synaptic transmission onto Purkinje cells, increasing the amplitude and frequency of inhibitory postsynaptic currents; no change in the frequency of action potentials from molecular layer interneurons was noted. The observed decreases in Purkinje cell action potential output could contribute to toluene-evoked impairments in cerebellar and motor functions. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. Music improves verbal memory encoding while decreasing prefrontal cortex activity: an fNIRS study.

    PubMed

    Ferreri, Laura; Aucouturier, Jean-Julien; Muthalib, Makii; Bigand, Emmanuel; Bugaiska, Aurelia

    2013-01-01

    Listening to music engages the whole brain, thus stimulating cognitive performance in a range of non-purely musical activities such as language and memory tasks. This article addresses an ongoing debate on the link between music and memory for words. While evidence on healthy and clinical populations suggests that music listening can improve verbal memory in a variety of situations, it is still unclear what specific memory process is affected and how. This study was designed to explore the hypothesis that music specifically benefits the encoding part of verbal memory tasks, by providing a richer context for encoding and therefore less demand on the dorsolateral prefrontal cortex (DLPFC). Twenty-two healthy young adults were subjected to functional near-infrared spectroscopy (fNIRS) imaging of their bilateral DLPFC while encoding words in the presence of either a music or a silent background. Behavioral data confirmed the facilitating effect of music background during encoding on subsequent item recognition. fNIRS results revealed significantly greater activation of the left hemisphere during encoding (in line with the HERA model of memory lateralization) and a sustained, bilateral decrease of activity in the DLPFC in the music condition compared to silence. These findings suggest that music modulates the role played by the DLPFC during verbal encoding, and open perspectives for applications to clinical populations with prefrontal impairments, such as elderly adults or Alzheimer's patients.

  12. Music improves verbal memory encoding while decreasing prefrontal cortex activity: an fNIRS study

    PubMed Central

    Ferreri, Laura; Aucouturier, Jean-Julien; Muthalib, Makii; Bigand, Emmanuel; Bugaiska, Aurelia

    2013-01-01

    Listening to music engages the whole brain, thus stimulating cognitive performance in a range of non-purely musical activities such as language and memory tasks. This article addresses an ongoing debate on the link between music and memory for words. While evidence on healthy and clinical populations suggests that music listening can improve verbal memory in a variety of situations, it is still unclear what specific memory process is affected and how. This study was designed to explore the hypothesis that music specifically benefits the encoding part of verbal memory tasks, by providing a richer context for encoding and therefore less demand on the dorsolateral prefrontal cortex (DLPFC). Twenty-two healthy young adults were subjected to functional near-infrared spectroscopy (fNIRS) imaging of their bilateral DLPFC while encoding words in the presence of either a music or a silent background. Behavioral data confirmed the facilitating effect of music background during encoding on subsequent item recognition. fNIRS results revealed significantly greater activation of the left hemisphere during encoding (in line with the HERA model of memory lateralization) and a sustained, bilateral decrease of activity in the DLPFC in the music condition compared to silence. These findings suggest that music modulates the role played by the DLPFC during verbal encoding, and open perspectives for applications to clinical populations with prefrontal impairments, such as elderly adults or Alzheimer’s patients. PMID:24339807

  13. Decreased expression of nociceptin/orphanin FQ in the dorsal anterior cingulate cortex of suicides.

    PubMed

    Lutz, Pierre-Eric; Zhou, Yi; Labbe, Aurélie; Mechawar, Naguib; Turecki, Gustavo

    2015-11-01

    The nociceptin/orphanin FQ (N/OFQ)-Nociceptin Opiod-like Peptide (NOP) receptor system is a critical mediator of physiological and pathological processes involved in emotional regulation and drug addiction. As such, this system may be an important biological substrate underlying psychiatric conditions that contribute to the risk of suicide. Thus, the goal of the present study was to characterize changes in human N/OFQ and NOP signaling as a function of depression, addiction and suicide. We quantified the expression of N/OFQ and NOP by RT-PCR in the anterior insula, the mediodorsal thalamus, and the dorsal anterior cingulate cortex (dACC) from a large sample of individuals who died by suicide and matched psychiatrically-healthy controls. Suicides displayed an 18% decrease in the expression of N/OFQ in the dACC that was not accounted for by current depressive or substance use disorders at the time of death. Therefore, our results suggest that dysregulation of the N/OFQ-NOP system may contribute to the neurobiology of suicide, a hypothesis that warrants further exploration.

  14. Decreased Expression of Nociceptin/Orphanin FQ in the dorsal Anterior Cingulate Cortex of Suicides

    PubMed Central

    Lutz, Pierre-Eric; Zhou, Yi; Labbe, Aurélie; Mechawar, Naguib; Turecki, Gustavo

    2015-01-01

    The nociceptin/orphanin FQ (N/OFQ) – Nociceptin Opiod-like Peptide (NOP) receptor system is a critical mediator of physiological and pathological processes involved in emotional regulation and drug addiction. As such, this system may be an important biological substrate underlying psychiatric conditions that contribute to the risk of suicide. Thus, the goal of the present study was to characterize changes in human N/OFQ and NOP signaling as a function of depression, addiction and suicide. We quantified the expression of N/OFQ and NOP by RT-PCR in the anterior insula, the mediodorsal thalamus, and the dorsal anterior cingulate cortex (dACC) from a large sample of individuals who died by suicide and matched psychiatrically-healthy controls. Suicides displayed an 18% decrease in the expression of N/OFQ in the dACC that was not accounted for by current depressive or substance use disorders at the time of death. Therefore, our results suggest that dysregulation of the N/OFQ-NOP system may contribute to the neurobiology of suicide, a hypothesis that warrants further exploration. PMID:26349406

  15. Repeated phencyclidine administration alters glutamate release and decreases GABA markers in the prefrontal cortex of rats

    PubMed Central

    Amitai, Nurith; Kuczenski, Ronald; Behrens, M. Margarita; Markou, Athina

    2011-01-01

    Repeated phencyclidine (PCP) administration induces cognitive disruptions resembling those seen in schizophrenia. Alterations in glutamate transmission and γ-aminobutyric acid (GABA) function in the prefrontal cortex (PFC) have been implicated in these PCP-induced deficits, as well as in cognitive symptoms of schizophrenia. PCP-induced cognitive deficits are reversed by chronic treatment with the atypical antipsychotic clozapine in rats. We investigated the effects of a single injection vs. repeated administration of PCP on glutamate levels in the PFC using in vivo microdialysis. Furthermore, we examined how these PCP regimens affect GABA neuronal markers in the PFC. Finally, we investigated the effects of clozapine on disruptions in glutamate levels and GABA neuronal markers induced by repeated PCP administration. Acute PCP administration (2 mg/kg) increased extracellular PFC glutamate; this increase appeared blunted, but was not eliminated, after repeated PCP pretreatment. PCP administration also strongly decreased levels of parvalbumin and glutamic acid decarboxylase-67 (two markers of GABA function) in the PFC, an effect that was maintained after a 10 day drug-free washout period and unaltered by the resumption of repeated PCP injections. All of the observed PCP effects were attenuated by chronic treatment with clozapine, an atypical antipsychotic that has partial effectiveness on cognitive impairment in schizophrenia. These findings suggest that abnormal cortical glutamate transmission, possibly driven by pathological changes in GABA function in parvalbumin-positive fast-spiking interneurons, may underlie some of the cognitive deficits in schizophrenia. A better understanding of glutamate and GABA dysregulation in schizophrenia may uncover new treatment targets for schizophrenia-related cognitive dysfunction. PMID:21238466

  16. Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A

    PubMed Central

    2012-01-01

    Abstact Background Gamma amino butyric acid (GABA), the principal inhibitory neurotransmitter in the cerebral cortex, maintains the inhibitory tones that counter balances neuronal excitation. When this balance is perturbed, seizures may ensue. Methods In the present study, alterations of the general GABA, GABAA and GABAB receptors in the cerebral cortex of the epileptic rat and the therapeutic application of Bacopa monnieri were investigated. Results Scatchard analysis of [3H]GABA, [3H]bicuculline and [3H]baclofen in the cerebral cortex of the epileptic rat showed significant decrease in Bmax (P < 0.001) compared to control. Real Time PCR amplification of GABA receptor subunits such as GABAAά1, GABAAγ, GABAAδ, GABAB and GAD where down regulated (P < 0.001) in epileptic rats. GABAAά5 subunit and Cyclic AMP responsible element binding protein were up regulated. Confocal imaging study confirmed the decreased GABA receptors in epileptic rats. Epileptic rats have deficit in radial arm and Y maze performance. Conclusions Bacopa monnieri and Bacoside-A treatment reverses epilepsy associated changes to near control suggesting that decreased GABA receptors in the cerebral cortex have an important role in epileptic occurrence; Bacopa monnieri and Bacoside-A have therapeutic application in epilepsy management. PMID:22364254

  17. Decreased Premotor Cortex Volume in Victims of Urban Violence with Posttraumatic Stress Disorder

    PubMed Central

    Rocha-Rego, Vanessa; Pereira, Mirtes G.; Oliveira, Leticia; Mendlowicz, Mauro V.; Fiszman, Adriana; Marques-Portella, Carla; Berger, William; Chu, Carlton; Joffily, Mateus; Moll, Jorge; Mari, Jair J.; Figueira, Ivan; Volchan, Eliane

    2012-01-01

    Background Studies addressing posttraumatic stress disorder (PTSD) have demonstrated that PTSD patients exhibit structural abnormalities in brain regions that relate to stress regulation and fear responses, such as the hippocampus, amygdala, anterior cingulate cortex, and ventromedial prefrontal cortex. Premotor cortical areas are involved in preparing to respond to a threatening situation and in representing the peripersonal space. Urban violence is an important and pervasive cause of human suffering, especially in large urban centers in the developing world. Violent events, such as armed robbery, are very frequent in certain cities, and these episodes increase the risk of PTSD. Assaultive trauma is characterized by forceful invasion of the peripersonal space; therefore, could this traumatic event be associated with structural alteration of premotor areas in PTSD? Methodology/Principal Findings Structural magnetic resonance imaging scans were acquired from a sample of individuals that had been exposed to urban violence. This sample consisted of 16 PTSD patients and 16 age- and gender-matched controls. Psychometric questionnaires differentiated PTSD patients from trauma-exposed controls with regard to PTSD symptoms, affective, and resilience predispositions. Voxel-based morphometric analysis revealed that, compared with controls, the PTSD patients presented significant reductions in gray matter volume in the ventral premotor cortex and in the pregenual anterior cingulate cortex. Conclusions Volume reduction in the premotor cortex that is observed in victims of urban violence with PTSD may be associated with a disruption in the dynamical modulation of the safe space around the body. The finding that PTSD patients presented a smaller volume of pregenual anterior cingulate cortex is consistent with the results of other PTSD neuroimaging studies that investigated different types of traumatic events. PMID:22952599

  18. Decreased Anterior Cingulate Cortex γ-Aminobutyric Acid in Youth With Tourette's Disorder.

    PubMed

    Freed, Rachel D; Coffey, Barbara J; Mao, Xiangling; Weiduschat, Nora; Kang, Guoxin; Shungu, Dikoma C; Gabbay, Vilma

    2016-12-01

    γ-Aminobutyric acid has been implicated in the pathophysiology of Tourette's disorder. The present study primarily sought to examine in vivo γ-aminobutyric acid levels in the anterior cingulate cortex in psychotropic medication-free adolescents and young adults. Secondarily, we sought to determine associations between γ-aminobutyric acid in the anterior cingulate cortex and measures of tic severity, tic-related impairment, and anxiety and depression symptoms. γ-Aminobutyric acid levels were measured using proton magnetic resonance spectroscopy. Analysis of covariance compared γ-aminobutyric acid levels in 15 youth with Tourette's disorder (mean age = 15.0, S.D. = 2.7) and 36 healthy comparison subjects (mean age = 15.9, S.D. = 2.1). Within the Tourette disorder group, we examined correlations between γ-aminobutyric acid levels and tic severity and tic-related impairment, as well as anxiety and depression severity. Anterior cingulate cortex γ-aminobutyric acid levels were lower in participants with Tourette's disorder compared with control subjects. Within the Tourette disorder group, γ-aminobutyric acid levels did not correlate with any clinical measures. Our findings support a role for γ-aminobutyric acid in Tourette's disorder. Larger prospective studies will further elucidate this role. Copyright © 2016. Published by Elsevier Inc.

  19. Oxygen pre-breathing decreases dysbaric diseases in UW sheep undergoing hyperbaric exposure.

    PubMed

    Sobakin, A S; Wilson, M A; Lehner, C E; Dueland, R T; Gendron-Fitzpatrick, A P

    2008-01-01

    Prolonged exposure of humans and animals to increased pressure as in a disabled submarine (DISSUB) can saturate the body's tissues with dissolved N2 as compressed air is breathed. Decompression-induced bubble formation in the long bone marrow cavity may lead to a bone compartment syndrome resulting in bone ischemia and necrosis. We tested oxygen pre-breathing prior to decompression in sheep to assess the effect upon dysbaric osteonecrosis (DON) induction in a DISSUB simulation experiment. A total of sixteen adult female sheep were used throughout the experiment. Four sheep were used as controls without oxygen pre-breathing. All sheep (99 +/- 14 kg SD) underwent dry chamber air exposure at 60 fsw (2.79 atm abs) (.2827 MPa) for 24 h followed by oxygen (88-92%) pre-breathing (15-min, 1-h, and 2-h and air for control) before "dropout" decompression at 30 fsw/min (0.91 atm/min). 99mTc-methylene diphosphonate (MDP) bone scans of the distal (radii and tibiae) long bones were used to detect "hot spots" of remodeling suggestive of DON lesions. Alizarin complexone fluorochrome was injected to visualize sites of metabolic activity indicating DON repair of both the proximal and distal long bones (radii, tibiae, femora, and humeri). Our findings showed that the amount of alizarin complexone deposition and bone scan uptake was greater in sheep with shorter oxygen pre-breathing times than those undergoing longer pre-breathing dives (p = 0.0056 and p = 0.001, for one and two hour pre-breathes respectively). Proximal limb bones (femur, humerus) displayed less alizarin complexone deposition than the distal radius and tibia (p < 0.0001).

  20. Stimulation of medial prefrontal cortex decreases the responsiveness of central amygdala output neurons.

    PubMed

    Quirk, Gregory J; Likhtik, Ekaterina; Pelletier, Joe Guillaume; Paré, Denis

    2003-09-24

    In extinction of auditory fear conditioning, rats learn that a tone no longer predicts the occurrence of a footshock. Recent lesion and unit recording studies suggest that the medial prefrontal cortex (mPFC) plays an essential role in the inhibition of conditioned fear following extinction. mPFC has robust projections to the amygdala, a structure that is known to mediate the acquisition and expression of conditioned fear. Fear conditioning potentiates the tone responses of neurons in the basolateral amygdala (BLA), which excite neurons in the central nucleus (Ce) of the amygdala. In turn, the Ce projects to the brainstem and hypothalamic areas that mediate fear responses. The present study was undertaken to test the hypothesis that the mPFC inhibits conditioned fear via feedforward inhibition of Ce output neurons. Recording extracellularly from physiologically identified brainstem-projecting Ce neurons, we tested the effect of mPFC prestimulation on Ce responsiveness to synaptic input. In support of our hypothesis, mPFC prestimulation dramatically reduced the responsiveness of Ce output neurons to inputs from the insular cortex and BLA. Thus, our findings support the idea that mPFC gates impulse transmission from the BLA to Ce, perhaps through GABAergic intercalated cells, thereby gating the expression of conditioned fear.

  1. Intraoperative Optimization to Decrease Postoperative PRBC Transfusion in Children Undergoing Craniofacial Reconstruction

    PubMed Central

    Nguyen, Thanh T.; Lam, Humphrey V.; Phillips, Maxie; Edwards, Clasherrol; Austin, Thomas M.

    2014-01-01

    Background Craniofacial reconstructive surgery for craniosynostosis is associated with large blood loss and intraoperative transfusion. This blood loss may continue through the initial postoperative period, potentially resulting in transfusion postoperatively. The purpose of this study is to determine if there is an association between any modifiable intraoperative factors and postoperative blood transfusion in this patient population. Methods A cohort of 55 pediatric patients who underwent primary craniofacial reconstruction at Vanderbilt Children’s Hospital from January 1, 2013 to April 31, 2014 was analyzed. The authors analyzed 20 different demographic and perioperative variables for statistical associations with postoperative PRBC transfusion using multiple logistic regression with optimal models being selected by Bayesian Model Averaging. Results The optimal regression model only included initial PACU Hct as a predictor and showed a significant association between this variable and postoperative PRBC transfusion (odds ratio 0.69, 95%CI 0.55–0.87, P = 0.0016). Based on the average decrease in postoperative hematocrit (Hct) and the postoperative transfusion trigger, an initial PACU Hct threshold of 30 was calculated. In our patient sample, an initial PACU Hct above 30 was associated with a 50% decrease in the absolute risk of receiving a PRBC transfusion postoperatively. Conclusions Based on this retrospective analysis, it may be justifiable to transfuse residual volume from previously exposed intraoperative PRBCs to a Hct above 30 to decrease the likelihood of subsequent blood transfusions from different donors in the postoperative period. PMID:25495602

  2. Severe nutritional risk predicts decreased long-term survival in geriatric patients undergoing pancreaticoduodenectomy for benign disease.

    PubMed

    Sanford, Dominic E; Sanford, Angela M; Fields, Ryan C; Hawkins, William G; Strasberg, Steven M; Linehan, David C

    2014-12-01

    Weight loss and malnutrition are poorly tolerated by geriatric patients, and pancreaticoduodenectomy (PD) can result in chronic malabsorption and weight loss. We sought to determine how preoperative severe nutritional risk (SNR), as defined by the American College of Surgeons National Surgical Quality Improvement Program/American Geriatric Society Best Practice Guidelines, affects long-term survival after PD for benign disease among geriatric and nongeriatric patients. All patients undergoing PD for nonmalignant conditions at a single center between 1995 and 2013 were followed for survival, excluding patients who died within 90 days of surgery. Survival of geriatric (age ≥65 years) and nongeriatric (age <65 years) patients with and without SNR was compared using Kaplan Meier methods. Cox regression was performed. There were 320 patients who underwent PD for benign disease. Over the course of the study, the proportion of geriatric patients undergoing PD for benign conditions increased from 25% to 46%. In addition to being older, geriatric patients undergoing PD for benign disease were significantly more likely to have coronary artery disease (CAD) and hypertension. Geriatric patients with preoperative SNR had significantly decreased long-term survival after PD for benign disease (p < 0.001), with roughly 1 in 3 patients dead at 5 years compared with 1 in 14 patients without SNR. Survival was not significantly different among nongeriatric patients with and without SNR. In geriatric patients, age, CAD, and SNR were significantly associated with decreased survival on both univariate and multivariate analysis. Severe nutritional risk can be a useful predictor of long-term survival in geriatric patients undergoing PD, and could improve patient risk stratification preoperatively. Nonoperative management should be strongly considered in geriatric patients with SNR, when malignancy is not suspected. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc

  3. Decreased GABAB Receptors in the Cingulate Cortex and Fusiform Gyrus in Autism

    PubMed Central

    Gibbs, Terrell T.; Blatt, Gene J.

    2010-01-01

    Autism is a behaviorally defined neurodevelopmental disorder and among its symptoms are disturbances in face and emotional processing. Emerging evidence demonstrates abnormalities in the GABAergic (gamma-aminobutyric acid) system in autism, which likely contributes to these deficits. GABAB receptors play an important role in modulating synapses and maintaining the balance of excitation-inhibition in the brain. The density of GABAB receptors in subjects with autism and matched controls was quantified in the anterior and posterior cingulate cortex, important for socio-emotional and cognitive processing, and the fusiform gyrus, important for identification of faces and facial expressions. Significant reductions in GABAB receptor density were demonstrated in all three regions examined suggesting that alterations in this key inhibitory receptor subtype may contribute to the functional deficits in individuals with autism. Interestingly, the presence of seizure in a subset of autism cases did not have a significant effect on the density of GABAB receptors in any of the three regions. PMID:20557420

  4. Electro-acupuncture decreases postoperative pain and improves recovery in patients undergoing a supratentorial craniotomy.

    PubMed

    An, Li-Xin; Chen, Xue; Ren, Xiu-Jun; Wu, Hai-Feng

    2014-01-01

    We performed this study to examine the effect of electro-acupuncture (EA) on postoperative pain, postoperative nausea and vomiting (PONV) and recovery in patients after a supratentorial tumor resection. Eighty-eight patients requiring a supratentorial tumor resection were anesthetized with sevoflurane and randomly allocated to a no treatment group (Group C) or an EA group (Group A). After anesthesia induction, the patients in Group A received EA at LI4 and SJ5, at BL63 and LR3 and at ST36 and GB40 on the same side as the craniotomy. The stimulation was continued until the end of the operation. Patient-controlled intravenous analgesia (PCIA) was used for the postoperative analgesia. The postoperative pain scores, PONV, the degree of dizziness and appetite were recorded. In the first 6 hours after the operation, the mean total bolus, the effective times of PCIA bolus administrations and the VAS scores were much lower in the EA group (p < 0.05). In the EA group, the incidence of PONV and degree of dizziness and feeling of fullness in the head within the first 24 hours after the operation was much lower than in the control group (p < 0.05). In the EA group, more patients had a better appetite than did the patients in group C (51.2% vs. 27.5%) (p < 0.05). The use of EA in neurosurgery patients improves the quality of postoperative analgesia, promotes appetite recovery and decreases some uncomfortable sensations, such as dizziness and feeling of fullness in the head.

  5. Increases in the right dorsolateral prefrontal cortex and decreases the rostral prefrontal cortex activation after-8 weeks of focused attention based mindfulness meditation.

    PubMed

    Tomasino, Barbara; Fabbro, Franco

    2016-02-01

    Mindfulness meditation is a form of attention control training. The training exercises the ability to repeatedly focus attention. We addressed the activation changes related to an 8-weeks mindfulness-oriented focused attention meditation training on an initially naïve subject cohort. Before and after training participants underwent an fMRI experiment, thus, although not strictly a cross over design, they served as their internal own control. During fMRI they exercised focused attention on breathing and body scan as compared to resting. We found increased and decreased activation in different parts of the prefrontal cortex (PFC) by comparing pre- vs. post-mindfulness training (MT) during breathing and body scan meditation exercises that were compared against their own resting state. In the post-MT (vs. pre-MT) meditation increased activation in the right dorsolateral PFC and in the left caudate/anterior insula and decreased activation in the rostral PFC and right parietal area 3b. Thus a brief mindfulness training caused increased activation in areas involved in sustaining and monitoring the focus of attention (dorsolateral PFC), consistent with the aim of mindfulness that is exercising focused attention mechanisms, and in the left caudate/anterior insula involved in attention and corporeal awareness and decreased activation in areas part of the "default mode" network and is involved in mentalizing (rostral PFC), consistent with the ability trained by mindfulness of reducing spontaneous mind wandering.

  6. High levels of neuroticism are associated with decreased cortical folding of the dorsolateral prefrontal cortex.

    PubMed

    Christoph Schultz, C; Warziniak, Heide; Koch, Kathrin; Schachtzabel, Claudia; Güllmar, Daniel; Reichenbach, Jürgen R; Schlösser, Ralf G; Sauer, Heinrich; Wagner, Gerd

    2017-04-06

    The personality trait neuroticism has been identified as a vulnerability factor for common psychiatric diseases and defining potential neuroanatomical markers for early recognition and prevention strategies is mandatory. Because both personality traits and cortical folding patterns are early imprinted and timely stable there is reason to hypothesize an association between neuroticism and cortical folding. Thus, to identify a putative linkage, we tested whether the degree of neuroticism is associated with local cortical folding in a sample of 109 healthy individuals using a surface-based MRI approach. Based on previous findings we additionally tested for a potential association with cortical thickness. We found a highly significant negative correlation between the degree of neuroticism and local cortical folding of the left dorsolateral prefrontal cortex (DLPFC), i.e., high levels of neuroticism were associated with low cortical folding of the left DLPFC. No association was found with cortical thickness. The present study is the first to describe a linkage between the extent of local cortical folding and the individual degree of neuroticism in healthy subjects. Because neuroticism is a vulnerability factor for common psychiatric diseases such as depression our finding indicates that alterations of DLPFC might constitute a neurobiological marker elevating risk for psychiatric burden.

  7. Decreased norepinephrine (NE) uptake in cerebral cortex and inferior colliculus of genetically epilepsy prone (GEP) rats

    SciTech Connect

    Browning, R.A.; Rigler-Daugherty, S.K.; Long, G.; Jobe, P.C.; Wade, D.R.

    1986-03-01

    GEP rats are characterized by an enhanced susceptibility to seizures caused by a variety of stimuli, most notably sound. Pharmacological treatments that reduce the synaptic concentration of NE increase seizure severity in GEP rats while elevations in NE have the opposite effect. GEP rats also display a widespread deficit in brain NE concentration suggesting that their increased seizure susceptibility is related to a deficit in noradrenergic transmission. The authors have compared the kinetics of /sup 3/H-NE uptake in the P/sub 2/ synaptosomal fraction isolated from the cerebral cortex of normal and GEP-rats. Although the apparent Kms were not significantly different (Normal +/- SEM:0.37 +/- 0.13..mu..M; GEP +/- SEM: 0.29 +/- 0.07..mu..M), the Vmax for GEP rats was 48% lower than that of normal rats (Normal +/- SEM: 474 +/- 45 fmole/mg/4min; GEP +/- SEM: 248 +/- 16 fmole/mg/4min). Because of the possible role of the inferior colliculus (IC) in the initiation of sound-induced seizures in GEP rats, the authors measured synaptosomal NE uptake in the IC using a NE concentration of 50 nM. The IC synaptosomal NE uptake was found to be 35% lower in GEP than in normal rats. These findings are consistent with the hypothesis that a deficit in noradrenergic transmission is related to the increased seizure susceptibility of GEP rats.

  8. Ketamine is effective in decreasing the incidence of emergence agitation in children undergoing dental repair under sevoflurane general anesthesia.

    PubMed

    Abu-Shahwan, Ibrahim; Chowdary, Khalid

    2007-09-01

    Emergence agitation or delirium is a known phenomenon that may occur in children undergoing general anesthesia with inhaled agents. Our aim was to test the hypothesis that the addition of a small dose of ketamine at the end of sevoflurane anesthesia will result in a decrease in the incidence and severity of such phenomenon. We performed a randomized double blind study involving 85 premedicated children 4-7 years old undergoing dental repair. Children were premedicated with acetaminophen and midazolam. Anesthesia was induced and maintained with sevoflurane in N2O/O2. Group K received ketamine 0.25 mg.kg (-1) and Group S received saline. We evaluated recovery characteristics upon awakening and during the first 30 min using the Pediatric Anesthesia Emergence Delirium scale. Eighty of the 85 enrolled children completed the study. There were 42 children in Group I. Emergence agitation was diagnosed in seven children in the ketamine group (16.6%) and in 13 children in the placebo group (34.2%). There was no difference in time to meet recovery room discharge criteria between the two groups. We conclude that the addition of ketamine 0.25 mg.kg(-1) can decrease the incidence of emergence agitation in children after sevoflurane general anesthesia.

  9. 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

  10. Age-Dependent Decrease and Alternative Splicing of Methionine Synthase mRNA in Human Cerebral Cortex and an Accelerated Decrease in Autism

    PubMed Central

    Muratore, Christina R.; Hodgson, Nathaniel W.; Trivedi, Malav S.; Abdolmaleky, Hamid M.; Persico, Antonio M.; Lintas, Carla; De La Monte, Suzanne; Deth, Richard C.

    2013-01-01

    The folate and vitamin B12-dependent enzyme methionine synthase (MS) is highly sensitive to cellular oxidative status, and lower MS activity increases production of the antioxidant glutathione, while simultaneously decreasing more than 200 methylation reactions, broadly affecting metabolic activity. MS mRNA levels in postmortem human cortex from subjects across the lifespan were measured and a dramatic progressive biphasic decrease of more than 400-fold from 28 weeks of gestation to 84 years was observed. Further analysis revealed alternative splicing of MS mRNA, including deletion of folate-binding domain exons and age-dependent deletion of exons from the cap domain, which protects vitamin B12 (cobalamin) from oxidation. Although three species of MS were evident at the protein level, corresponding to full-length and alternatively spliced mRNA transcripts, decreasing mRNA levels across the lifespan were not associated with significant changes in MS protein or methionine levels. MS mRNA levels were significantly lower in autistic subjects, especially at younger ages, and this decrease was replicated in cultured human neuronal cells by treatment with TNF-α, whose CSF levels are elevated in autism. These novel findings suggest that rather than serving as a housekeeping enzyme, MS has a broad and dynamic role in coordinating metabolism in the brain during development and aging. Factors adversely affecting MS activity, such as oxidative stress, can be a source of risk for neurological disorders across the lifespan via their impact on methylation reactions, including epigenetic regulation of gene expression. PMID:23437274

  11. Transcranial magnetic stimulation of early visual cortex suppresses conscious representations in a dichotomous manner without gradually decreasing their precision.

    PubMed

    Koivisto, Mika; Harjuniemi, Inari; Railo, Henry; Salminen-Vaparanta, Niina; Revonsuo, Antti

    2017-09-01

    Transcranial magnetic stimulation (TMS) of early visual cortex can suppresses visual perception at early stages of processing. The suppression can be measured both with objective forced-choice tasks and with subjective ratings of visual awareness, but there is lack of objective evidence on how and whether the TMS influences the quality of representations. Does TMS decrease the precision of representations in graded manner, or does it lead to dichotomous, "all-or-nothing" suppression. We resolved this question by using a continuous measure of the perceptual error: the observers had to perceive the orientation of a target (Landort-C) and to adjust the orientation of a probe to match that of the target. Mixture modeling was applied to estimate the probability of guess trials and the standard deviation of the non-guess trials. TMS delivered 60-150 ms after stimulus-onset influenced only the guessing rate, whereas the standard deviation (i.e., precision) was not affected. This suggests that TMS suppressed representations dichotomously without affecting their precision. The guessing probability correlated with subjective visibility ratings, suggesting that it measured visual awareness. In a control experiment, manipulation of the stimulus contrast affected the standard deviation of the errors, indicating that contrast has a gradual influence on the precision of representations. The findings suggest that TMS of early visual cortex suppresses perception in dichotomous manner by decreasing the signal-to-noise ratio by increasing the noise level, whereas reduction of the signal level (i.e., contrast) decreases the precision of representations. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Decreasing predictability of visual motion enhances feed-forward processing in visual cortex when stimuli are behaviorally relevant.

    PubMed

    Kellermann, Thilo; Scholle, Ruben; Schneider, Frank; Habel, Ute

    2017-03-01

    Recent views of information processing in the (human) brain emphasize the hierarchical structure of the central nervous system, which is assumed to form the basis of a functional hierarchy. Hierarchical predictive processing refers to the notion that higher levels try to predict activity in lower areas, while lower levels transmit a prediction error up the hierarchy whenever the predictions fail. The present study aims at testing hypothetical modulatory effects of unpredictable visual motion on forward connectivities within the visual cortex. Functional magnetic resonance imaging was acquired from 35 healthy volunteers while viewing a moving ball under three different levels of predictability. In two different runs subjects were asked to attend to direction changes in the ball's motion, where a button-press was required in one of these runs only. Dynamic causal modeling was applied to a network comprising V1, V5 and posterior parietal cortex in the right hemisphere. The winning model of a Bayesian model selection indicated an enhanced strength in the forward connection from V1 to V5 with decreasing predictability for the run requiring motor response. These results support the notion of hierarchical predictive processing in the sense of an augmented bottom-up transmission of prediction error with increasing uncertainty about motion direction. This finding may be of importance for promoting our understanding of trait characteristics in psychiatric disorders, as an increased forward propagation of prediction error is assumed to underlie schizophrenia and may be observable at early stages of the disease.

  13. Parafascicular thalamic nucleus deep brain stimulation decreases NMDA receptor GluN1 subunit gene expression in the prefrontal cortex.

    PubMed

    Fernández-Cabrera, Mónica R; Selvas, Abraham; Miguéns, Miguel; Higuera-Matas, Alejandro; Vale-Martínez, Anna; Ambrosio, Emilio; Martí-Nicolovius, Margarita; Guillazo-Blanch, Gemma

    2017-04-21

    The rodent parafascicular nucleus (PFn) or the centromedian-parafascicular complex of primates is a posterior intralaminar nucleus of the thalamus related to cortical activation and maintenance of states of consciousness underlying attention, learning and memory. Deep brain stimulation (DBS) of the PFn has been proved to restore arousal and consciousness in humans and to enhance performance in learning and memory tasks in rats. The primary expected effect of PFn DBS is to induce plastic changes in target neurons of brain areas associated with cognitive function. In this study, Wistar rats were stimulated for 20mins in the PFn following a DBS protocol that had previously facilitated memory in rats. NMDA and GABAB receptor binding, and gene expression of the GluN1subunit of the NMDA receptor (NMDAR) were assessed in regions related to cognitive functions, such as the prefrontal cortex and hippocampus. The results showed that PFn DBS induced a decrease in NMDAR GluN1 subunit gene expression in the cingulate and prelimbic cortices, but no significant statistical differences were found in the density of NMDA or GABAB receptors in any of the analyzed regions. Taken together, our findings suggest a possible role for the NMDAR GluN1 subunit in the prefrontal cortex in the procognitive actions of the PFn DBS.

  14. Decreased 16:0/20:4-phosphatidylinositol level in the post-mortem prefrontal cortex of elderly patients with schizophrenia

    PubMed Central

    Matsumoto, Junya; Nakanishi, Hiroki; Kunii, Yasuto; Sugiura, Yuki; Yuki, Dai; Wada, Akira; Hino, Mizuki; Niwa, Shin-Ichi; Kondo, Takeshi; Waki, Michihiko; Hayasaka, Takahiro; Masaki, Noritaka; Akatsu, Hiroyasu; Hashizume, Yoshio; Yamamoto, Sakon; Sato, Shinji; Sasaki, Takehiko; Setou, Mitsutoshi; Yabe, Hirooki

    2017-01-01

    The etiology of schizophrenia includes phospholipid abnormalities. Phospholipids are bioactive substances essential for brain function. To analyze differences in the quantity and types of phospholipids present in the brain tissue of patients with schizophrenia, we performed a global analysis of phospholipids in multiple brain samples using liquid chromatography electrospray ionization mass/mass spectrometry (LC-ESI/MS/MS) and imaging mass spectrometry (IMS). We found significantly decreased 16:0/20:4-phosphatidylinositol (PI) levels in the prefrontal cortex (PFC) in the brains from patients with schizophrenia in the LC-ESI/MS/MS, and that the 16:0/20:4-PI in grey matter was most prominently diminished according to the IMS experiments. Previous reports investigating PI pathology of schizophrenia did not identify differences in the sn-1 and sn-2 fatty acyl chains. This study is the first to clear the fatty acid composition of PI in brains from patients with schizophrenia. Alteration in the characteristic fatty acid composition of PI may also affect neuronal function, and could play a role in the etiology of schizophrenia. Although further studies are necessary to understand the role of reduced 16:0/20:4-PI levels within the prefrontal cortex in the etiology of schizophrenia, our results provide insight into the development of a novel therapy for the clinical treatment of schizophrenia. PMID:28332626

  15. Decreased 16:0/20:4-phosphatidylinositol level in the post-mortem prefrontal cortex of elderly patients with schizophrenia.

    PubMed

    Matsumoto, Junya; Nakanishi, Hiroki; Kunii, Yasuto; Sugiura, Yuki; Yuki, Dai; Wada, Akira; Hino, Mizuki; Niwa, Shin-Ichi; Kondo, Takeshi; Waki, Michihiko; Hayasaka, Takahiro; Masaki, Noritaka; Akatsu, Hiroyasu; Hashizume, Yoshio; Yamamoto, Sakon; Sato, Shinji; Sasaki, Takehiko; Setou, Mitsutoshi; Yabe, Hirooki

    2017-03-23

    The etiology of schizophrenia includes phospholipid abnormalities. Phospholipids are bioactive substances essential for brain function. To analyze differences in the quantity and types of phospholipids present in the brain tissue of patients with schizophrenia, we performed a global analysis of phospholipids in multiple brain samples using liquid chromatography electrospray ionization mass/mass spectrometry (LC-ESI/MS/MS) and imaging mass spectrometry (IMS). We found significantly decreased 16:0/20:4-phosphatidylinositol (PI) levels in the prefrontal cortex (PFC) in the brains from patients with schizophrenia in the LC-ESI/MS/MS, and that the 16:0/20:4-PI in grey matter was most prominently diminished according to the IMS experiments. Previous reports investigating PI pathology of schizophrenia did not identify differences in the sn-1 and sn-2 fatty acyl chains. This study is the first to clear the fatty acid composition of PI in brains from patients with schizophrenia. Alteration in the characteristic fatty acid composition of PI may also affect neuronal function, and could play a role in the etiology of schizophrenia. Although further studies are necessary to understand the role of reduced 16:0/20:4-PI levels within the prefrontal cortex in the etiology of schizophrenia, our results provide insight into the development of a novel therapy for the clinical treatment of schizophrenia.

  16. COMPARISON OF INTRAOPERATIVE KETAMINE VS. FENTANYL USE DECREASES POSTOPERATIVE OPIOID REQUIREMENTS IN TRAUMA PATIENTS UNDERGOING CERVICAL SPINE SURGERY.

    PubMed

    Berkowitz, Aviva C; Ginsburg, Aryeh M; Pesso, Raymond M; Angus, George L D; Kang, Amiee; Ginsburg, Dov B

    2016-02-01

    Postoperative airway compromise following cervical spine surgery is a potentially serious adverse event. Residual effects of anesthesia and perioperative opioids that can cause both sedation and respiratory depression further increase this risk. Ketamine is an N-methyl-d-aspartate (NMDA) receptor antagonist that provides potent analgesia without noticeable respiratory depression. We investigated whether intraoperative ketamine administration could decrease perioperative opioid requirements in trauma patients undergoing cervical spine surgery. We retrospectively reviewed anesthesia records identifying cervical spine surgeries performed between March 2014 and February 2015. All patients received a balanced anesthetic technique utilizing sevoflurane 0.5 minimum alveolar concentration (MAC) and propofol infusion (50-100 mcg/kg/min). For intraoperative analgesia, one group of patients received ketamine (N=25) and a second group received fentanyl (N=27). Cumulative opioid doses in the recovery room and until 24 hours postoperatively were recorded. Fewer patients in the ketamine group (11/25 [44%] vs. 20/27 [74%], respectively; p = 0.03) required analgesics in the recovery room. Additionally, the total cumulative opioid requirements in the ketamine group decreased postoperatively at both 3 and 6 hours (p = 0.01). Ketamine use during cervical spine surgery decreased opioid requirements in both the recovery room and in the first 6 hours postoperatively. This may have the potential to minimize opioid induced respiratory depression in a population at increased risk of airway complications related to the surgical procedure.

  17. Sustained decrease in oxygenated hemoglobin during video games in the dorsal prefrontal cortex: a NIRS study of children.

    PubMed

    Matsuda, Goh; Hiraki, Kazuo

    2006-02-01

    Traditional neuroimaging studies have mainly focused on brain activity derived from a simple stimulus and task. Therefore, little is known about brain activity during daily operations. In this study, we investigated hemodynamic changes in the dorsal prefrontal cortex (DPFC) during video games as one of daily amusements, using near infrared spectroscopy technique. It was previously reported that oxygenated hemoglobin (oxyHb) in adults' DPFC decreased during prolonged game playing time. In the present study, we examined whether similar changes were observed in children. Twenty children (7-14 years old) participated in our study, but only 13 of them were eventually subject to analysis. They played one or two commercially available video games; namely a fighting and a puzzle game, for 5 min. We used changes in concentration of oxyHb as an indicator of brain activity and consequently, most of the children exhibited a sustained game-related oxyHb decrease in DPFC. Decrease patterns of oxyHb in children during video game playing time did not differ from those in adults. There was no significant correlation between ages or game performances and changes in oxyHb. These findings suggest that game-related oxyHb decrease in DPFC is a common phenomenon to adults and children at least older than 7 years old, and we suggest that this probably results from attention demand from the video games rather than from subject's age and performance.

  18. Continuous theta burst stimulation over the left dorsolateral prefrontal cortex decreases medium load working memory performance in healthy humans.

    PubMed

    Schicktanz, Nathalie; Fastenrath, Matthias; Milnik, Annette; Spalek, Klara; Auschra, Bianca; Nyffeler, Thomas; Papassotiropoulos, Andreas; de Quervain, Dominique J-F; Schwegler, Kyrill

    2015-01-01

    The dorsolateral prefrontal cortex (DLPFC) plays a key role in working memory. Evidence indicates that transcranial magnetic stimulation (TMS) over the DLPFC can interfere with working memory performance. Here we investigated for how long continuous theta-burst stimulation (cTBS) over the DLPFC decreases working memory performance and whether the effect of cTBS on performance depends on working memory load. Forty healthy young subjects received either cTBS over the left DLPFC or sham stimulation before performing a 2-, and 3-back working memory letter task. An additional 0-back condition served as a non-memory-related control, measuring general attention. cTBS over the left DLPFC significantly impaired 2-back working memory performance for about 15 min, whereas 3-back and 0-back performances were not significantly affected. Our results indicate that the effect of left DLPFC cTBS on working memory performance lasts for roughly 15 min and depends on working memory load.

  19. Attending multiple items decreases the selectivity of population responses in human primary visual cortex.

    PubMed

    Anderson, David E; Ester, Edward F; Serences, John T; Awh, Edward

    2013-05-29

    Multiple studies have documented an inverse relationship between the number of to-be-attended or remembered items in a display ("set size") and task performance. The neural source of this decline in cognitive performance is currently under debate. Here, we used a combination of fMRI and a forward encoding model of orientation selectivity to generate population tuning functions for each of two stimuli while human observers attended either one or both items. We observed (1) clear population tuning functions for the attended item(s) that peaked at the stimulus orientation and decreased monotonically as the angular distance from this orientation increased, (2) a set-size-dependent decline in the relative precision of orientation-specific population responses, such that attending two items yielded a decline in selectivity of the population tuning function for each item, and (3) that the magnitude of the loss of precision in population tuning functions predicted individual differences in the behavioral cost of attending an additional item. These findings demonstrate that attending multiple items degrades the precision of perceptual representations for the target items and provides a straightforward account for the associated impairments in visually guided behavior.

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

    PubMed

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

    2016-12-20

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

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

    PubMed Central

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

    2017-01-01

    Abstract Previous research suggests that people show increased self-referential processing when they provide criticism to others, and that this self-referential processing can have negative effects on interpersonal perceptions and behavior. The current research hypothesized that adopting a self-distanced perspective (i.e. thinking about a situation from a non-first person point of view), as compared with a typical self-immersed perspective (i.e. thinking about a situation from a first-person point of view), would reduce self-referential processing during the provision of criticism, and in turn improve interpersonal perceptions and behavior. We tested this hypothesis in an interracial context since research suggests that self-referential processing plays a role in damaging interracial relations. White participants prepared for mentorship from a self-immersed or self-distanced perspective. They then conveyed negative and positive evaluations to a Black mentee while electroencephalogram (EEG) was recorded. Source analysis revealed that priming a self-distanced (vs self-immersed) perspective predicted decreased activity in regions linked to self-referential processing (medial prefrontal cortex; MPFC) when providing negative evaluations. This decreased MPFC activity during negative evaluations, in turn, predicted verbal feedback that was perceived to be more positive, warm and helpful. Results suggest that self-distancing can improve interpersonal perceptions and behavior by decreasing self-referential processing during the provision of criticism. PMID:27998998

  2. The activity of the primary motor cortex ipsilateral to the exercising hand decreases during repetitive handgrip exercise.

    PubMed

    Shibuya, Kenichi

    2011-12-01

    The brain function controlling muscle force production is not yet fully understood. The purpose of this study was to examine bilateral primary motor cortex (M1) oxygenation during static-handgrip exercises performed with the right hand (60% maximal voluntary contraction; 10 s exercise/75 s rest; five sets). Twelve healthy, right-handed male subjects participated in this study. Near-infrared spectroscopy probes were positioned over the bilateral M1 to measure cortical oxygenation during handgrip exercises. The maximum values of the changes in concentrations of oxyhemoglobin (HbO(2)) and deoxyhemoglobin (Hb) across the trials (i) did not change significantly during the contralateral M1 activation (p > 0.05), whereas (ii) in the case of the ipsilateral M1 activation a significant (p < 0.05) decrease in HbO(2) and a significant (p < 0.01) decrease in Hb could be measured. The activation in ipsilateral M1 at the fifth trial was significantly decreased compared with that in the first trial (HbO(2): p < 0.001; Hb: p < 0.001). The present results suggest that the ipsilateral M1 is recruited during the motor task in compensation for the contralateral M1 and the habituation to motor task might alter the efficiency for interaction of the ipsilateral M1 to the contralateral M1. The interhemispheric interaction might change due to habituation to motor task.

  3. Somatosensory and visual deprivation each decrease the density of parvalbumin neurons and their synapse terminals in the prefrontal cortex and hippocampus of mice.

    PubMed

    Ueno, Hiroshi; Shoshi, Chikafumi; Suemitsu, Shunsuke; Usui, Shinichi; Sujiura, Hiroko; Okamoto, Motoi

    2013-01-01

    In the phenomenon known as cross-modal plasticity, the loss of one sensory system is followed by improved functioning of other intact sensory systems. MRI and functional MRI studies suggested a role of the prefrontal cortex and the temporal lobe in cross-modal plasticity. We used a mouse model to examine the effects of sensory deprivation achieved by whisker trimming and visual deprivation achieved by dark rearing in neonatal mice on the appearance of parvalbumin (PV) neurons and the formation of glutamic acid decarboxylase 67 (GAD67)-positive puncta around pyramidal neurons in the prefrontal cortex and hippocampus. Whisker trimming, but not dark rearing, decreased the density of PV neurons in the hippocampus at postnatal day 28 (P28). In the prefrontal cortex, whisker trimming and dark rearing decreased the density of PV neurons in layer 5/6 (L5/6) at P28 and in L2/3 at P56, respectively, whereas dark rearing increased the density of PV neurons in L5/6 at P56. Whisker trimming decreased the density of GAD67-positive puncta in CA1 of the hippocampus at both P28 and P56 and in L5/6 of the prefrontal cortex at P28. Dark rearing decreased the density of GAD67-positive puncta in CA1 of the hippocampus and in both L2/3 and L5/6 of the prefrontal cortex at P28, and in L2/3 of the prefrontal cortex at P56. These results demonstrate that somatosensory or visual deprivation causes changes in the PV-interneuronal network in the mouse prefrontal cortex and hippocampus. The results also suggest that the alteration of the PV-interneuronal network, especially in the prefrontal cortex, may contribute to cross-modal plasticity.

  4. Disruption of Akt signaling decreases dopamine sensitivity in modulation of inhibitory synaptic transmission in rat prefrontal cortex.

    PubMed

    Li, Yan-Chun; Yang, Sha-Sha; Gao, Wen-Jun

    2016-09-01

    Akt is a serine/threonine kinase, which is dramatically reduced in the prefrontal cortex (PFC) of patients with schizophrenia, and a deficiency in Akt1 results in PFC function abnormalities. Although the importance of Akt in dopamine (DA) transmission is well established, how impaired Akt signaling affects the DA modulation of synaptic transmission in the PFC has not been characterized. Here we show that Akt inhibitors significantly decreased receptor sensitivity to DA by shifting DA modulation of GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) in prefrontal cortical neurons. Akt inhibition caused a significant decrease in synaptic dopamine D2 receptor (D2R) levels with high-dose DA exposure. In addition, Akt inhibition failed to affect DA modulation of IPSCs after blockade of β-arrestin 2. β-arrestin 2-mediated interaction of clathrin with D2R was enhanced by co-application of a Akt inhibitor and DA. Taken together, the reduced response in DA modulation of inhibitory transmission mainly involved β-arrestin 2-dependent D2R desensitization. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Microglial numbers attain adult levels after undergoing a rapid decrease in cell number in the third postnatal week.

    PubMed

    Nikodemova, Maria; Kimyon, Rebecca S; De, Ishani; Small, Alissa L; Collier, Lara S; Watters, Jyoti J

    2015-01-15

    During postnatal development, microglia, CNS resident innate immune cells, are essential for synaptic pruning, neuronal apoptosis and remodeling. During this period microglia undergo morphological and phenotypic transformations; however, little is known about how microglial number and density is regulated during postnatal CNS development. We found that after an initial increase during the first 14 postnatal days, microglial numbers in mouse brain began declining in the third postnatal week and were reduced by 50% by 6weeks of age; these "adult" levels were maintained until at least 9months of age. Microglial CD11b levels increased, whereas CD45 and ER-MP58 declined between P10 and adulthood, consistent with a maturing microglial phenotype. Our data indicate that both increased microglial apoptosis and a decreased proliferative capacity contribute to the developmental reduction in microglial numbers. We found no correlation between developmental reductions in microglial numbers and brain mRNA levels of Cd200, Cx3Cl1, M-Csf or Il-34. We tested the ability of M-Csf-overexpression, a key growth factor promoting microglial proliferation and survival, to prevent microglial loss in the third postnatal week. Mice overexpressing M-Csf in astrocytes had higher numbers of microglia at all ages tested. However, the developmental decline in microglial numbers still occurred, suggesting that chronically elevated M-CSF is unable to overcome the developmental decrease in microglial numbers. Whereas the identity of the factor(s) regulating microglial number and density during development remains to be determined, it is likely that microglia respond to a "maturation" signal since the reduction in microglial numbers coincides with CNS maturation. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Decreased insulin-like growth factor-I and its receptor expression in the hippocampus and somatosensory cortex of the aged mouse.

    PubMed

    Lee, Choong Hyun; Ahn, Ji Hyeon; Park, Joon Ha; Yan, Bing Chun; Kim, In Hye; Lee, Dae Hwan; Cho, Jeong-Hwi; Chen, Bai Hui; Lee, Jae-Chul; Cho, Jun Hwi; Lee, Yun Lyul; Won, Moo-Ho; Kang, Il-Jun

    2014-04-01

    Insulin-like growth factor-I (IGF-I) is a multifunctional polypeptide and has diverse effects on brain functions. In the present study, we compared IGF-I and IGF-I receptor (IGF-IR) immunoreactivity and their protein levels between the adult (postnatal month 6) and aged (postnatal month 24) mouse hippocampus and somatosensory cortex. In the adult hippocampus, IGF-I immunoreactivity was easily observed in the pyramidal cells of the stratum pyramidale in the hippocampus proper and in the granule cells of the granule cell layer of the dentate gyrus. In the adult somatosensory cortex, IGF-I immunoreactivity was easily found in the pyramidal cells of layer V. In the aged groups, IGF-I expression was dramatically decreased in the cells. Like the change of IGF-I immunoreactivity, IGF-IR immunoreactivity in the pyramidal and granule cells of the hippocampus and in the pyramidal cells of the somatosensory cortex was also markedly decreased in the aged group. In addition, both IGF-I and IGF-IR protein levels were significantly decreased in the aged hippocampus and somatosensory cortex. These results indicate that the apparent decrease of IGF-I and IGF-IR expression in the aged mouse hippocampus and somatosensory cortex may be related to age-related changes in the aged brain.

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

    PubMed

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

    2016-03-15

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

  8. Decreased prefrontal cortex dopamine activity following adolescent social defeat in male rats: role of dopamine D2 receptors

    PubMed Central

    Watt, Michael J.; Roberts, Christina L.; Scholl, Jamie L.; Meyer, Danielle L.; Miiller, Leah C.; Barr, Jeffrey L.; Novick, Andrew M.; Renner, Kenneth J.; Forster, Gina L.

    2014-01-01

    Rationale Adverse social experience in adolescence causes reduced medial prefrontal cortex (mPFC) dopamine (DA) and associated behavioral deficits in early adulthood. Objective To determine whether mPFC DA hypofunction following social stress is specific to adolescent experience, and if this results from stress-induced DA D2 receptor activation. Materials and Methods Male rats exposed to repeated social defeat during adolescence or adulthood had mPFC DA activity sampled 17 days later. Separate experiments used freely-moving microdialysis to measure mPFC DA release in response to adolescent defeat exposure. At P40, 49 and 56 mPFC DA turnover was assessed to identify when DA activity decreased in relation to the adolescent defeat experience. Finally, non-defeated adolescent rats received repeated intra-mPFC infusions of the D2 receptor agonist quinpirole, while another adolescent group received intra-mPFC infusions of the D2 antagonist amisulpride before defeat exposure. Results Long-term decreases or increases in mPFC DA turnover were observed following adolescent or adult defeat, respectively. Adolescent defeat exposure elicits sustained increases in mPFC DA release, and DA turnover remains elevated beyond the stress experience before declining to levels below normal at P56. Activation of mPFC D2 receptors in non-defeated adolescents decreases DA activity in a similar manner to that caused by adolescent defeat, while defeat-induced reductions in mPFC DA activity are prevented by D2 receptor blockade. Conclusions Both the developing and mature PFC DA systems are vulnerable to social stress, but only adolescent defeat causes DA hypofunction. This appears to result in part from stress-induced activation of mPFC D2 autoreceptors. PMID:24271009

  9. Decreased cholinergic function in the cerebral cortex of hypoxic neonatal rats: role of glucose, oxygen and epinephrine resuscitation.

    PubMed

    Anju, T R; Smijin, S; Chinthu, R; Paulose, C S

    2012-01-15

    Molecular processes regulating cholinergic functions play an important role in the control of respiration under hypoxia. Cholinergic alterations and its further complications in learning and memory due to hypoxic insult in neonatal rats and the effect of glucose, oxygen and epinephrine resuscitation was evaluated in the present study. Receptor binding and gene expression studies were done in the cerebral cortex to analyze the changes in total muscarinic receptors, muscarinic M1, M2, M3 receptors and the enzymes involved in acetylcholine metabolism - choline acetyltransferase and acetylcholine esterase. Neonatal hypoxia decreased total muscarinic receptors with reduced muscarinic M1, M2 and M3 receptor genes. The reduction in acetylcholine metabolism is indicated by the down regulated choline acetyltransferase and up regulated acetylcholine esterase expression. These cholinergic disturbances were reversed to near control in glucose resuscitated hypoxic neonates. The adverse effects of immediate oxygenation and epinephrine administration are also reported. This has immense clinical significance in establishing a proper resuscitation for the management of neonatal hypoxia.

  10. Cold or calculating? Reduced activity in the subgenual cingulate cortex reflects decreased emotional aversion to harming in counterintuitive utilitarian judgment

    PubMed Central

    Wiech, Katja; Kahane, Guy; Shackel, Nicholas; Farias, Miguel; Savulescu, Julian; Tracey, Irene

    2013-01-01

    Recent research on moral decision-making has suggested that many common moral judgments are based on immediate intuitions. However, some individuals arrive at highly counterintuitive utilitarian conclusions about when it is permissible to harm other individuals. Such utilitarian judgments have been attributed to effortful reasoning that has overcome our natural emotional aversion to harming others. Recent studies, however, suggest that such utilitarian judgments might also result from a decreased aversion to harming others, due to a deficit in empathic concern and social emotion. The present study investigated the neural basis of such indifference to harming using functional neuroimaging during engagement in moral dilemmas. A tendency to counterintuitive utilitarian judgment was associated both with ‘psychoticism’, a trait associated with a lack of empathic concern and antisocial tendencies, and with ‘need for cognition’, a trait reflecting preference for effortful cognition. Importantly, only psychoticism was also negatively correlated with activation in the subgenual cingulate cortex (SCC), a brain area implicated in empathic concern and social emotions such as guilt, during counterintuitive utilitarian judgments. Our findings suggest that when individuals reach highly counterintuitive utilitarian conclusions, this need not reflect greater engagement in explicit moral deliberation. It may rather reflect a lack of empathic concern, and diminished aversion to harming others. PMID:23280149

  11. Continuous Theta Burst Stimulation over the Left Dorsolateral Prefrontal Cortex Decreases Medium Load Working Memory Performance in Healthy Humans

    PubMed Central

    Schicktanz, Nathalie; Fastenrath, Matthias; Milnik, Annette; Spalek, Klara; Auschra, Bianca; Nyffeler, Thomas; Papassotiropoulos, Andreas; de Quervain, Dominique J.-F.; Schwegler, Kyrill

    2015-01-01

    The dorsolateral prefrontal cortex (DLPFC) plays a key role in working memory. Evidence indicates that transcranial magnetic stimulation (TMS) over the DLPFC can interfere with working memory performance. Here we investigated for how long continuous theta-burst stimulation (cTBS) over the DLPFC decreases working memory performance and whether the effect of cTBS on performance depends on working memory load. Forty healthy young subjects received either cTBS over the left DLPFC or sham stimulation before performing a 2-, and 3-back working memory letter task. An additional 0-back condition served as a non-memory-related control, measuring general attention. cTBS over the left DLPFC significantly impaired 2-back working memory performance for about 15 min, whereas 3-back and 0-back performances were not significantly affected. Our results indicate that the effect of left DLPFC cTBS on working memory performance lasts for roughly 15 min and depends on working memory load. PMID:25781012

  12. Cold or calculating? Reduced activity in the subgenual cingulate cortex reflects decreased emotional aversion to harming in counterintuitive utilitarian judgment.

    PubMed

    Wiech, Katja; Kahane, Guy; Shackel, Nicholas; Farias, Miguel; Savulescu, Julian; Tracey, Irene

    2013-03-01

    Recent research on moral decision-making has suggested that many common moral judgments are based on immediate intuitions. However, some individuals arrive at highly counterintuitive utilitarian conclusions about when it is permissible to harm other individuals. Such utilitarian judgments have been attributed to effortful reasoning that has overcome our natural emotional aversion to harming others. Recent studies, however, suggest that such utilitarian judgments might also result from a decreased aversion to harming others, due to a deficit in empathic concern and social emotion. The present study investigated the neural basis of such indifference to harming using functional neuroimaging during engagement in moral dilemmas. A tendency to counterintuitive utilitarian judgment was associated both with 'psychoticism', a trait associated with a lack of empathic concern and antisocial tendencies, and with 'need for cognition', a trait reflecting preference for effortful cognition. Importantly, only psychoticism was also negatively correlated with activation in the subgenual cingulate cortex (SCC), a brain area implicated in empathic concern and social emotions such as guilt, during counterintuitive utilitarian judgments. Our findings suggest that when individuals reach highly counterintuitive utilitarian conclusions, this need not reflect greater engagement in explicit moral deliberation. It may rather reflect a lack of empathic concern, and diminished aversion to harming others.

  13. Inefficiency in Self-organized Attentional Switching in the Normal Aging Population is Associated with Decreased Activity in the Ventrolateral Prefrontal Cortex

    PubMed Central

    Hampshire, Adam; Gruszka, Aleksandra; Fallon, Sean J.; Owen, Adrian M.

    2010-01-01

    Studies of the aging brain have demonstrated that areas of the frontal cortex, along with their associated top–down executive control processes, are particularly prone to the neurodegenerative effects of age. Here, we investigate the effects of aging on brain and behavior using a novel task, which allows us to examine separate components of an individual's chosen strategy during routine problem solving. Our findings reveal that, contrary to previous suggestions of a specific decrease in cognitive flexibility, older participants show no increased level of perseveration to either the recently rewarded object or the recently relevant object category. In line with this lack of perseveration, lateral and medial regions of the orbito-frontal cortex, which are associated with inhibitory control and reward processing, appear to be functionally intact. Instead, a general loss of efficient problem-solving strategy is apparent with a concomitant decrease in neural activity in the ventrolateral prefrontal cortex and the posterior parietal cortex. The dorsolateral prefrontal cortex is also affected during problem solving, but age-related decline within this region appears to occur at a later stage. PMID:18345987

  14. Transcranial magnetic stimulation of the left dorsolateral prefrontal cortex decreases cue-induced nicotine craving and EEG delta power.

    PubMed

    Pripfl, Jürgen; Tomova, Livia; Riecansky, Igor; Lamm, Claus

    2014-01-01

    TMS has high potential as smoking cessation treatment. However, the neural mechanisms underlying TMS induced reduction of tobacco craving remain unclear. Electroencephalographic (EEG) delta frequency has been associated with the activity of the dopaminergic brain reward system, which is crucial for nicotine induced effects, and decreases after nicotine admission in smokers. The aim of this study was to investigate EEG delta power changes induced by hf rTMS of the left dorsolateral prefrontal cortex (DLPFC) in nicotine deprived smokers and it's relation to cue-induced nicotine craving. Fourteen healthy smokers meeting ICD-10 criteria for tobacco addiction participated in this within-subject sham controlled study. Participants had to abstain from smoking 6 h before the experiment. Effects of high-frequency repetitive TMS (hf rTMS) (10 Hz) for verum (left DLPFC) and sham (vertex) stimulations on cue-induced nicotine craving and resting state EEG delta power were assessed before and three times within 40 min after rTMS. Both craving (P = 0.046) and EEG delta power (P = 0.048) were significantly lower after verum stimulation compared to sham stimulation across the whole post stimulation time period assessed. However, changes of craving ratings and delta power did not correlate. Hf rTMS applied to the left DLPFC reduces nicotine craving in short-term abstinent smokers. Changes in delta activity support the idea that stimulation induced effects are mediated by the dopaminergic brain reward system, which presumably plays a prominent, but probably not exclusive, role in this stimulation induced behavioral modulation, making this method a promising smoking cessation treatment candidate. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Decreased density of GABA-A receptors in the left sensorimotor cortex in akinetic catatonia: investigation of in vivo benzodiazepine receptor binding

    PubMed Central

    Northoff, G.; Steinke, R.; Czcervenka, C.; Krause, R.; Ulrich, S.; Danos, P.; Kropf, D.; Otto, H.; Bogerts, B.

    1999-01-01

    OBJECTIVES—Catatonia is a psychomotor syndrome with concomittant akinesia and anxiety which both respond almost immediately to benzodiazepines such as lorazepam. The benzodiazepine receptor distribution was therefore investigated in akinetic catatonia with single photon emission tomography (SPECT) using iodine-123-iomazenil (123 I Iomazenil).
METHODS—Ten akinetic catatonic patients, 10 psychiatric controls (similar age, sex, medication, and underlying psychiatric diagnosis but without catatonic syndrome), and 20 healthy controls were investigated with SPECT 2 hours after injection of 123 I Iomazenil. To exclude potential effects of cerebral perfusion (r-CBF) r-CBF was additionally investigated with Tc-99mECD SPECT.
RESULTS—Catatonic patients showed significantly lower iomazenil binding and altered right-left relations in the left sensorimotor cortex compared with psychiatric (p<0.001) and healthy (p<0.001) controls. In addition, there was significantly lower r-CBF in the right lower prefrontal and parietal cortex in catatonia whereas in the left sensorimotor cortex no differences in r-CBF between groups were found. Catatonic motor and affective symptoms showed significant correlations (p<0.05) with benzodiazepine binding in the left sensorimotor cortex as well as with right parietal r-CBF.
CONCLUSIONS—Reduced iomazenil binding suggests decreased density of GABA-A receptors in the left sensorimotor cortex in akinetic catatonia. In addition to reduced GABA-A receptor density in the left sensorimotor cortex the parietal cortex seems to be involved in pathophysiology of catatonic symptoms. It is concluded that, considering results from correlation analyses, both emotional and motor symptoms in catatonia seem to be closely related to left sensorimotor and right parietal alterations.

 PMID:10486389

  16. Environmental enrichment and working memory tasks decrease hippocampal cell proliferation after wheel running--A role for the prefrontal cortex in hippocampal plasticity?

    PubMed

    Schaefers, Andrea T U

    2015-10-22

    Despite an increasing amount of evidence about the regulation of adult hippocampal neurogenesis on the local level, less attention has been paid to its systemic embedding in wider brain circuits. The aim of the present study was to obtain evidence for a potential role of the prefrontal cortex in the regulation of adult hippocampal neurogenesis. We hypothesised that activation of the prefrontal cortex by environmental enrichment or a working-memory task would decrease previously enhanced cell proliferation rates. Wheel running was applied as a common stimulator of cell proliferation in CD1 mice reared under deprivation of natural environmental stimulation. Next, the animals were assigned to four groups for different treatments in the following three days: housing under continued deprivation, environmental enrichment, a spatial-delayed alternation task in an automated T-maze that activates the prefrontal cortex by working-memory requirements or a control task in the automated T-maze differing only in the single parameter working-memory-associated delay. Both the environmental enrichment and spatial-delayed alternation tasks decreased cell proliferation rates in the dentate gyrus compared to deprived housing and the control task in the T-maze. As the control animals underwent the same procedures and stressors and differed only in the single parameter working-memory-associated delay, the working-memory requirement seems to be the crucial factor for decreasing cell proliferation rates. Taken together, these results suggest that the prefrontal cortex may play a role in the regulation of hippocampal cell proliferation.

  17. Fluoride and Arsenic Exposure Impairs Learning and Memory and Decreases mGluR5 Expression in the Hippocampus and Cortex in Rats

    PubMed Central

    Jiang, Shoufang; Su, Jing; Yao, Sanqiao; Zhang, Yanshu; Cao, Fuyuan; Wang, Fei; Wang, Huihui; Li, Jun; Xi, Shuhua

    2014-01-01

    Fluoride and arsenic are two common inorganic contaminants in drinking water that are associated with impairment in child development and retarded intelligence. The present study was conducted to explore the effects on spatial learning, memory, glutamate levels, and group I metabotropic glutamate receptors (mGluRs) expression in the hippocampus and cortex after subchronic exposure to fluoride, arsenic, and a fluoride and arsenic combination in rats. Weaned male Sprague-Dawley rats were assigned to four groups. The control rats drank tap water. Rats in the three exposure groups drank water with sodium fluoride (120 mg/L), sodium arsenite (70 mg/L), and a sodium fluoride (120 mg/L) and sodium arsenite (70 mg/L) combination for 3 months. Spatial learning and memory was measured in Morris water maze. mGluR1 and mGluR5 mRNA and protein expression in the hippocampus and cortex was detected using RT-PCR and Western blot, respectively. Compared with controls, learning and memory ability declined in rats that were exposed to fluoride and arsenic both alone and combined. Combined fluoride and arsenic exposure did not have a more pronounced effect on spatial learning and memory compared with arsenic and fluoride exposure alone. Compared with controls, glutamate levels decreased in the hippocampus and cortex of rats exposed to fluoride and combined fluoride and arsenic, and in cortex of arsenic-exposed rats. mGluR5 mRNA and protein expressions in the hippocampus and mGluR5 protein expression in the cortex decreased in rats exposed to arsenic alone. Interestingly, compared with fluoride and arsenic exposure alone, fluoride and arsenic combination decreased mGluR5 mRNA expression in the cortex and protein expression in the hippocampus, suggesting a synergistic effect of fluoride and arsenic. These data indicate that fluoride and arsenic, either alone or combined, can decrease learning and memory ability in rats. The mechanism may be associated with changes of glutamate level and

  18. 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.

  19. Gender-specific decrease in NUDR and 5-HT1A receptor proteins in the prefrontal cortex of subjects with major depressive disorder.

    PubMed

    Szewczyk, Bernadeta; Albert, Paul R; Burns, Ariel M; Czesak, Margaret; Overholser, James C; Jurjus, George J; Meltzer, Herbert Y; Konick, Lisa C; Dieter, Lesa; Herbst, Nicole; May, Warren; Rajkowska, Grazyna; Stockmeier, Craig A; Austin, Mark C

    2009-03-01

    A variety of studies have documented alterations in 5-HT1A receptor binding sites in the brain of subjects with major depressive disorder (MDD). The recently identified transcription factor, nuclear deformed epidermal autoregulatory factor (NUDR/Deaf-1) has been shown to function as a transcriptional modulator of the human 5-HT1A receptor gene. The present study was undertaken to document the regional and cellular localization of NUDR in the human prefrontal cortex and to examine the levels of NUDR and 5-HT1A receptor protein in prefrontal cortex of female and male depressed and control subjects. NUDR immunoreactivity was present in neurons and glia across cortical layers and was co-localized with 5-HT1A receptor immunoreactive neurons. NUDR immunoreactivity as measured by Western blot was significantly decreased in the prefrontal cortex of female depressed subjects (42%, p=0.02) and unchanged in male depressed subjects relative to gender-matched control subjects. Similarly, 5-HT1A receptor protein level was significantly reduced in the prefrontal cortex of female depressed subjects (46%, p=0.03) and unchanged in male depressed subjects compared to gender-matched control subjects. Reduced protein expression of NUDR in the prefrontal cortex of female subjects with MDD may reflect a functional alteration in this transcription factor, which may contribute to the decrease in 5-HT1A receptors observed in the same female subjects with MDD. In addition, the gender-specific alterations in cortical NUDR and 5-HT1A receptor proteins could represent an underlying biological mechanism associated with the higher incidence of depression in women.

  20. Decreased [(3)H]spiperone binding in the anterior cingulate cortex of schizophrenia patients: an autoradiographic study.

    PubMed

    Zavitsanou, K; Huang, X F

    2002-01-01

    Abnormalities in the anterior cingulate cortex have been reported in patients with schizophrenia, and have been implicated in the pathophysiology of this disorder. In the present study, we have examined antipsychotic-sensitive binding sites in the left anterior cingulate cortex of schizophrenia patients and controls. Using quantitative autoradiography and [(3)H]spiperone as a ligand, both saturation and competition experiments were performed in post-mortem brain tissue obtained from six schizophrenia and six control cases. Saturation experiments revealed that the maximum number of [(3)H]spiperone binding sites was significantly reduced by 31% in the schizophrenia group as compared to the control group (65.3+/-5.6 fmol/mg tissue versus 94.2+/-7.3 fmol/mg tissue). Increased dissociation constant was also observed in the schizophrenia group (2.2+/-0.4 nM versus 1.3+/-0.2 nM), but was not statistically significant (P=0.07). Competition experiments were performed in order to examine the pharmacological profile of [(3)H]spiperone binding, and revealed that: (i) displacement of [(3)H]spiperone binding by clozapine and mianserin was significantly reduced in the schizophrenia group as compared to the control group (-26% and -16% respectively); (ii) the order of displacement potency of the drugs tested was: haloperidol>mianserin>butaclamol approximately risperidone>clozapine>2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene. Our results suggest a reduction of antipsychotic-sensitive binding sites in the anterior cingulate cortex of patients with schizophrenia. Such abnormality could lead to an imbalance in neurotransmitter regulation in the anterior cingulate cortex which may contribute to the emergence of some symptoms of schizophrenia.

  1. A Dipeptidyl Peptidase-4 Inhibitor, Teneligliptin, Decreases Plasma Triglyceride-Rich Lipoprotein Remnants in Diabetic Patients with Chronic Kidney Disease Undergoing Hemodialysis.

    PubMed

    Homma, Koichiro; Yoshizawa, Joe; Shiina, Yutaka; Ozawa, Hideki; Igarashi, Muneki; Matsuoka, Tadashi; Sasaki, Junichi; Yoshizawa, Mamoru; Homma, Yasuhiko

    2017-06-02

    A high plasma level of remnant-like particle cholesterol (RLP-C), which is equivalent to triglyceride-rich lipoprotein remnant, is an important coronary risk marker. RLP-C level is high, independent of other plasma lipids, in patients with chronic kidney disease (CKD) undergoing hemodialysis. The effect of teneligliptin, a dipeptidyl peptidase (DPP)-4 inhibitor, on plasma levels of RLP-C in patients with diabetes mellitus and CKD under hemodialysis was studied. Teneligliptin 20 mg/day was administered to 15 patients with diabetes and CKD undergoing hemodialysis for 12 weeks. Ten patients with diabetes and CKD undergoing hemodialysis were allocated to the control group. Blood was sampled following a 12-h fast. Fasting plasma glucose (FPG), C-peptide, triglyceride, low-density lipoprotein (LDL)-cholesterol (C), high-density lipoprotein (HDL)-C, RLP-C, apolipoprotein (apo) B, oxidized LDL, lipoprotein lipase, and glycated hemoglobin (HbA1c) were measured. HbA1c decreased in the teneligliptin group but significantly increased in the control group. FPG and RLP-C significantly decreased in the teneligliptin group. Plasma lipoprotein-related parameters except RLP-C were not affected by teneligliptin treatment. Teneligliptin treatment significantly reduced plasma levels of RLP-C, FPG, and HbA1c in patients with diabetes with CKD who are undergoing hemodialysis.

  2. Acute administration of nicotine into the higher order auditory Te2 cortex specifically decreases the fear-related charge of remote emotional memories.

    PubMed

    Cambiaghi, Marco; Grosso, Anna; Renna, Annamaria; Concina, Giulia; Sacchetti, Benedetto

    2015-12-01

    Nicotine elicits several behavioural effects on mood as well as on stress and anxiety processes. Recently, it was found that the higher order components of the sensory cortex, such as the secondary auditory cortex Te2, are essential for the long-term storage of remote fear memories. Therefore, in the present study, we examined the effects of acute nicotine injection into the higher order auditory cortex Te2, on the remote emotional memories of either threat or incentive experiences in rats. We found that intra-Te2 nicotine injection decreased the fear-evoked responses to a tone previously paired with footshock. This effect was cue- and dose-specific and was not due to any interference with auditory stimuli processing, innate anxiety and fear processes, or with motor responses. Nicotine acts acutely in the presence of threat stimuli but it did not determine the permanent degradation of the fear-memory trace, since memories tested one week after nicotine injection were unaffected. Remarkably, nicotine did not affect the memory of a similar tone that was paired to incentive stimuli. We conclude from our results that nicotine, when acting acutely in the auditory cortex, relieves the fear charge embedded by learned stimuli. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. 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.

  4. Perceived Occupational Stress is associated with Decreased Cortical Activity of the Prefrontal Cortex: A Multichannel Near-infrared Spectroscopy Study

    PubMed Central

    Chou, Po-Han; Lin, Wei-Hao; Hung, Chao-An; Chang, Chiung-Chih; Li, Wan-Rung; Lan, Tsuo-Hung; Huang, Min-Wei

    2016-01-01

    Despite an increasing number of reports on the associations between chronic occupational stress and structural and functional changes of the brain, the underlying neural correlates of perceived occupational stress is still not clear. Perceived stress reflects the extents to which situations are appraised as stressful at a given point in one’s life. Using near-infrared spectroscopy, we investigated the associations between perceived occupational stress and cortical activity over the bilateral frontotemporal regions during a verbal fluency test. Sixty-eight participants (17 men, 51 women), 20–62 years of age were recruited. Perceived occupational stress was measured using the Chinese version of Job Content Questionnaire, and the Chinese version of the Copenhagen Burnout Inventory. We found statistically significant negative associations between occupational burnout and brain cortical activity over the fronto-polar and dorsolateral prefrontal cortex during the VFT (r = −0.343 to −0.464). In conclusion, our research demonstrated a possible neural basis of perceived occupational stress that are distributed across the prefrontal cortex. PMID:27958364

  5. Light-Emitting Diode (LED) therapy improves occipital cortex damage by decreasing apoptosis and increasing BDNF-expressing cells in methanol-induced toxicity in rats.

    PubMed

    Ghanbari, Amir; Ghareghani, Majid; Zibara, Kazem; Delaviz, Hamdallah; Ebadi, Elham; Jahantab, Mohammad Hossein

    2017-03-17

    Methanol-induced retinal toxicity, frequently associated with elevated free radicals and cell edema, is characterized by progressive retinal ganglion cell (RGC) death and vision loss. Previous studies investigated the effect of photomodulation on RGCs, but not the visual cortex. In this study, the effect of 670nm Light-Emitting Diode (LED) therapy on RGCs and visual cortex recovery was investigated in a seven-day methanol-induced retinal toxicity protocol in rats. Methanol administration showed a reduction in the number of RGCs, loss of neurons (neuronal nuclear antigen, NeuN+), activation of glial fibrillary acidic protein (GFAP+) expressing cells, suppression of brain-derived neurotrophic factor (BDNF+) positive cells, increase in apoptosis (caspase 3+) and enhancement of nitric oxide (NO) release in serum and brain. On the other hand, LED therapy significantly reduced RGC death, in comparison to the methanol group. In addition, the number of BDNF positive cells was significantly higher in the visual cortex of LED-treated group, in comparison to methanol-intoxicated and control groups. Moreover, LED therapy caused a significant decrease in cell death (caspase 3+ cells) and a significant reduction in the NO levels, both in serum and brain tissue, in comparison to methanol-intoxicated rats. Overall, LED therapy demonstrated a number of beneficial effects in decreasing oxidative stress and in functional recovery of RGCs and visual cortex. Our data suggest that LED therapy could be a potential condidate as a non-invasive approach for treatment of retinal damage, which needs further clinicl studies.

  6. Decreased IDE and IGF2 expression but increased Aβ40 in the cerebral cortex of mouse pups by early life lead exposure.

    PubMed

    Li, Ning; Yang, Guojun; Wang, Yueying; Qiao, Mingwu; Zhang, Pingan; Shao, Jianfeng; Yang, Guoyu

    2016-03-01

    As the abbreviation of plumbum and a chemical symbol for lead, Pb produces neurotoxic effects, which result into an impairment of learning and memory and other neurological dysfunctions. However, the mechanism of neurotoxicity of Pb exposure is unclear. The present study was undertaken to investigate the effects of maternal lead exposure on expression of insulin-degrading enzyme (IDE),insulin-like growth factor 2 (IGF2) and beta amyloid protein 40 (Aβ40) in the cerebral cortex of mice offspring. Lead exposure initiated from beginning of gestation to weaning. Lead acetate administered in drinking solutions was dissolved in distilled deionized water at the concentrations of 0.1%, 0.2% and 0.5% groups respectively. On the 21st postnatal day, On the PND21, the learning and memory ability were tested by water maze test and the Pb levels were also determined by graphite furnace atomic absorption spectrometry. The expression of IDE, IGF2 and Aβ40 in cerebral cortex was examined by immunohistochemistry, immunofluorescence and western blotting. The lead levels in blood and cerebral cortex of all lead exposure groups were significantly higher than that of the control group (P<0.05). In water maze test, the performances of 0.5% and 1% lead exposure groups were worse than that of the control group (P<0.05).The expression of IDE and IGF2 was decreased, but Aβ40 was increased in lead exposed groups than that of the control group (P<0.05). The decreased expression of IDE and IGF2 and increased expression of Aβ40 in the cerebral cortex of pups may contribute to the neurotoxicity associated with maternal Pb exposure.

  7. Decrease of ERK/MAPK overactivation in prefrontal cortex reverses early memory deficit in a mouse model of Alzheimer's disease.

    PubMed

    Feld, Mariana; Krawczyk, María C; Sol Fustiñana, M; Blake, Mariano G; Baratti, Carlos M; Romano, Arturo; Boccia, Mariano M

    2014-01-01

    Alzheimer's disease (AD) can be considered as a disease of memory in its initial clinical stages. Amyloid-β (Aβ) peptide accumulation is central to the disease initiation leading later to intracellular neurofibrillary tangles (NFTs) of cytoskeletal tau protein formation. It is under discussion whether different Aβ levels of aggregation, concentration, brain area, and/or time of exposure might be critical to the disease progression, as well as which intracellular pathways it activates. The aim of the present work was to study memory-related early molecular and behavioral alterations in a mouse model of AD, in which a subtle deregulation of the physiologic function of Aβ can be inferred. For this purpose we used triple-transgenic (3xTg) mice, which develop Aβ and tau pathology resembling the disease progression in humans. Memory impairment in novel object recognition task was evident by 5 months of age in 3xTg mice. Hippocampus and prefrontal cortex extra-nuclear protein extracts developed differential patterns of Aβ aggregation. ERK1/MAPK showed higher levels of cytosolic activity at 3 months and higher levels of nuclear activity at 6 months in the prefrontal cortex. No significant differences were found in JNK and NF-κB activity and in calcineurin protein levels. Finally, intra-PFC administration of a MEK inhibitor in 6-month-old 3xTg mice was able to reverse memory impairment, suggesting that ERK pathway alterations might at least partially explain memory deficits observed in this model, likely as a consequence of memory trace disruption.

  8. 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

  9. Gelatine matrix with human thrombin decreases blood loss in adolescents undergoing posterior spinal fusion for idiopathic scoliosis: a multicentre, randomised clinical trial.

    PubMed

    Helenius, I; Keskinen, H; Syvänen, J; Lukkarinen, H; Mattila, M; Välipakka, J; Pajulo, O

    2016-03-01

    In a multicentre, randomised study of adolescents undergoing posterior spinal fusion for idiopathic scoliosis, we investigated the effect of adding gelatine matrix with human thrombin to the standard surgical methods of controlling blood loss. Patients in the intervention group (n = 30) were randomised to receive a minimum of two and a maximum of four units of gelatine matrix with thrombin in addition to conventional surgical methods of achieving haemostasis. Only conventional surgical methods were used in the control group (n = 30). We measured the intra-operative and total blood loss (intra-operative blood loss plus post-operative drain output). Each additional hour of operating time increased the intra-operative blood loss by 356.9 ml (p < 0.001) and the total blood loss by 430.5 ml (p < 0.001). Multiple linear regression analysis showed that the intervention significantly decreased the intra-operative (-171 ml, p = 0.025) and total blood loss (-177 ml, p = 0.027). The decrease in haemoglobin concentration from the day before the operation to the second post-operative day was significantly smaller in the intervention group (-6 g/l, p = 0.013) than in the control group. The addition of gelatine matrix with human thrombin to conventional methods of achieving haemostasis reduces both the intra-operative blood loss and the decrease in haemoglobin concentration post-operatively in adolescents undergoing posterior spinal fusion for idiopathic scoliosis. A randomised clinical trial showed that gelatine matrix with human thrombin decreases intra-operative blood loss by 30% when added to traditional surgical haemostatic methods in adolescents undergoing posterior spinal fusion for idiopathic scoliosis. ©2016 The British Editorial Society of Bone & Joint Surgery.

  10. Effectiveness of aromatherapy in decreasing maternal anxiety for a sick child undergoing infusion in a paediatric clinic.

    PubMed

    Ueki, Shingo; Niinomi, Kazuteru; Takashima, Yuko; Kimura, Ryoko; Komai, Kazuyo; Murakami, Kiyotaka; Fujiwara, Chieko

    2014-12-01

    We examined whether aromatherapy involving inhalation of yuzu (Citrus ichangensis×Citrus reticulata) oil was effective in decreasing mothers' anxiety for her sick child receiving an infusion at a paediatric clinic. Controlled clinical trial. Mothers of sick children who arrived at the hospital were asked to complete an anonymous questionnaire. After a doctor examined the child and confirmed the necessity for infusion, the mothers who agreed to participate in our study were allocated to an aromatherapy or a control group. A diffuser was filled with yuzu oil before the subjects entered the aromatherapy room. The mother was shown how to use the aromatherapy diffuser while the child was receiving an infusion in the same room. Fifteen minutes after entering the room, the mothers were asked to complete an another questionnaire. We measured the mother's anxiety with the state anxiety score from the State-Trait Anxiety Inventory. There were 60 subjects in the aromatherapy group and 61 in the control group. Both groups were well balanced in terms of demographic characteristics. Using analysis of variance, we demonstrated a significant difference in two-factor interactions between the control and aromatherapy groups. Maternal state anxiety was significantly lower in the aromatherapy than in the control group. Inhalation of yuzu oil was shown to decrease maternal anxiety for a sick child. A multicentre randomized controlled trial or double-blind study is necessary to obtain objective evidence of this benefit of aromatherapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Dry skin (xerosis) in patients undergoing maintenance haemodialysis: the role of decreased sweating of the eccrine sweat gland.

    PubMed

    Park, T H; Park, C H; Ha, S K; Lee, S H; Song, K S; Lee, H Y; Han, D S

    1995-12-01

    The aetiology and the pathophysiological mechanisms underlying the development of dry skin in uraemia are still unclear, but the hydration status of stratum corneum clearly influences the appearance of skin. The xerotic skin texture is often referred to as 'dry skin' and has been suggested as a cause of uraemic pruritus. To understand the aetiology of dry skin in uraemia we measured the status of skin surface hydration of uraemic patients with the corneometer and skin surface hydrometer, the functional capacity and the urea concentration of stratum corneum and the response of eccrine sweat gland to sudorific agent (0.05% pilocarpine HCL) in 18 age-matched haemodialysis patients and 10 healthy volunteers. We also performed the water sorption-desorption test to uraemic and control subjects after application of urea in various concentrations. Uraemic patient's skin showed decreased water content compared to control subjects. However, we found no correlation between dry skin and pruritus. Although the urea concentration of the horny layer in uraemic patients was elevated compared to control subjects (28.2 microgram/cm2 vs 5.04 micrograms/cm2, P < 0.05), its moisturizing effect to relieve pruritus is questionable because its artificial application revealed no improvement of the functional capacity of horny layer in concentration 5 times higher than the physiological concentration. Uraemic patients showed decreased sweating response to sudorific agent. In conclusion, the functional abnormalities of eccrine sweat glands may be account for dry skin in uraemic patients at least in part, but there is no correlation between xerosis and pruritus.

  12. 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.

  13. Blockade of NMDA receptors in postnatal period decreased density of tyrosine hydroxylase immunoreactive axonal arbors in the medial prefrontal cortex of adult rats.

    PubMed

    Wedzony, K; Fijał, K; Chocyk, A

    2005-06-01

    Malfunction of glutamatergic neurotransmission in postnatal period is considered to be a risk factor for development of schizophrenia. Thus, the present study investigates the impact of NMDA receptor blockade in the postnatal period on the density of tyrosine hydroxylase immunoreactive axonal arbors in the rat medial prefrontal cortex. Behavioral experiments revealed that adult rats (60 days old) treated in the postnatal period with a competitive antagonist of NMDA receptors, CGP 40116 (1.25 mg/kg on days 1, 3, 6, 9; 2.5 mg/kg on days 12, 15, 18; and finally 5 mg/kg on day 21, all injections s.c.), showed enhancement of the locomotor activity stimulated by quinpirole (0.3 mg/kg s.c.) and amphetamine (0.5 mg/kg s.c.), which suggests development of functional supersensitivity of dopaminergic systems. It has been found that CGP 40116, given in postnatal period decreased the density of tyrosine hydroxylase immunoreactive axonal arbors in the medial prefrontal cortex of adult animals. The decrease was observed in superficial (II/III) and deep (V/VI) layers of the medial prefrontal cortex, while the average length of tyrosine hydroxylase immunoreactive axonal arbors was increased in both superficial and deep cortical layers. Changes in the density of tyrosine hydroxylase immunoreactive axonal arbors have not been followed by a significant decrease in the content of tyrosine hydroxylase protein measured by Western blot. Thus, NMDA receptor blockade in the early period of life evokes changes in architecture of tyrosine hydroxylase immunoreactive axonal arbors and that malfunction of glutamatergic neurotransmission, in early period of life may produce anatomical changes which resemble those observed in the brains of schizophrenics.

  14. Decreasing Ventromedial Prefrontal Cortex Activity During Sequential Risk-Taking: An fMRI Investigation of the Balloon Analog Risk Task

    PubMed Central

    Schonberg, Tom; Fox, Craig R.; Mumford, Jeanette A.; Congdon, Eliza; Trepel, Christopher; Poldrack, Russell A.

    2012-01-01

    Functional imaging studies examining the neural correlates of risk have mainly relied on paradigms involving exposure to simple chance gambles and an economic definition of risk as variance in the probability distribution over possible outcomes. However, there is little evidence that choices made during gambling tasks predict naturalistic risk-taking behaviors such as drug use, extreme sports, or even equity investing. To better understand the neural basis of naturalistic risk-taking, we scanned participants using fMRI while they completed the Balloon Analog Risk Task, an experimental measure that includes an active decision/choice component and that has been found to correlate with a number of naturalistic risk-taking behaviors. In the task, as in many naturalistic settings, escalating risk-taking occurs under uncertainty and might be experienced either as the accumulation of greater potential rewards, or as exposure to increasing possible losses (and decreasing expected value). We found that areas previously linked to risk and risk-taking (bilateral anterior insula, anterior cingulate cortex, and right dorsolateral prefrontal cortex) were activated as participants continued to inflate balloons. Interestingly, we found that ventromedial prefrontal cortex (vmPFC) activity decreased as participants further expanded balloons. In light of previous findings implicating the vmPFC in value calculation, this result suggests that escalating risk-taking in the task might be perceived as exposure to increasing possible losses (and decreasing expected value) rather than the increasing potential total reward relative to the starting point of the trial. A better understanding of how neural activity changes with risk-taking behavior in the task offers insight into the potential neural mechanisms driving naturalistic risk-taking. PMID:22675289

  15. Motor overflow in children with attention-deficit/hyperactivity disorder is associated with decreased extent of neural activation in the motor cortex.

    PubMed

    Gaddis, Andrew; Rosch, Keri S; Dirlikov, Benjamin; Crocetti, Deana; MacNeil, Lindsey; Barber, Anita D; Muschelli, John; Caffo, Brian; Pekar, James J; Mostofsky, Stewart H

    2015-09-30

    Motor overflow is a developmental phenomenon that typically disappears by late childhood. Abnormal persistence of motor overflow is often present in children with attention-deficit/hyperactivity disorder (ADHD). This study employed functional magnetic resonance imaging (fMRI) during a finger-sequencing task to examine whether excessive motor overflow in children with ADHD is associated with decreased extent of motor circuit activation. Thirty-four right-handed children (18 typically developing controls, 16 ADHD) completed fMRI while performing a finger-sequencing task. Motor overflow was evaluated during a finger-sequencing task and a motor examination (the PANESS) performed outside the scanner. Diagnostic differences in behavioral measures of overflow and extent of activation in the contralateral and ipsilateral motor network ROIs were examined, along with correlations between overflow and extent of activation. Children with ADHD demonstrated greater overflow and lesser extent of activation in left primary motor cortex (BA4) and bilateral premotor cortex (BA6) and supplementary motor area (SMA) during right-hand finger-sequencing compared to controls. Decreased extent of primary motor and premotor activation correlated with increased hand-related overflow movements in children with ADHD but not controls. These findings suggest that overflow movements in children with ADHD may reflect decreased recruitment of neural circuitry involved in active inhibition of homologous motor circuitry unnecessary to task execution. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Early Decrease in Respiration and Uncoupling Event Independent of Cytochrome c Release in PC12 Cells Undergoing Apoptosis

    PubMed Central

    Berghella, Libera; Ferraro, Elisabetta

    2012-01-01

    Cytochrome c is a key molecule in mitochondria-mediated apoptosis. It also plays a pivotal role in cell respiration. The switch between these two functions occurs at the moment of its release from mitochondria. This process is therefore extremely relevant for the fate of the cell. Since cytochrome c mediates respiration, we studied the changes in respiratory chain activity during the early stages of apoptosis in order to contribute to unravel the mechanisms of cytochrome c release. We found that, during staurosporine (STS)- induced apoptosis in PC12 cells, respiration is affected before the release of cytochrome c, as shown by a decrease in the endogenous uncoupled respiration and an uncoupling event, both occurring independently of cytochrome c release. The decline in the uncoupled respiration occurs also upon Bcl-2 overexpression (which inhibits cytochrome c release), while the uncoupling event is inhibited by Bcl-2. We also observed that the first stage of nuclear condensation during STS-induced apoptosis does not depend on the release of cytochrome c into the cytosol and is a reversibile event. These findings may contribute to understand the mechanisms affecting mitochondria during the early stages of apoptosis and priming them for the release of apoptogenic factors. PMID:22666257

  17. Decreased Functional Connectivity of Insular Cortex in Drug Naïve First Episode Schizophrenia: In Relation to Symptom Severity

    PubMed Central

    Pang, Lijuan; Kennedy, David; Wei, Qinling; Lv, Luxian; Gao, Jinsong; Li, Hong; Quan, Meina; Li, Xue; Yang, Yongfeng; Fan, Xiaoduo; Song, Xueqin

    2017-01-01

    Background This study was to examine the insular cortical functional connectivity in drug naïve patients with first episode schizophrenia and to explore the relationship between the connectivity and the severity of clinical symptoms. Methods Thirty-seven drug naïve patients with schizophrenia and 25 healthy controls were enrolled in this study. A seed-based approach was used to analyze the resting-state functional imaging data. Insular cortical connectivity maps were bilaterally extracted for group comparison and validated by voxel-based morphometry (VBM) analysis. Clinical symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). Results There were significant reductions in the right insular cortical connectivity with the Heschl’s gyrus, anterior cingulate cortex (ACC), and caudate (p’s<0.001) in the patient group compared with the healthy control (HC) group. Reduced right insular cortical connectivity with the Heschl’s gyrus was further confirmed in the VBM analysis (FDR corrected p<0.05). Within the patient group, there was a significant positive relationship between the right insula-Heschl’s connectivity and PANSS general psychopathology scores (r = 0.384, p = 0.019). Conclusion Reduced insula-Heschl’s functional connectivity is present in drug naïve patients with first episode schizophrenia, which might be related to the manifestation of clinical symptoms. PMID:28107346

  18. Imipramine-induced c-Fos expression in the medial prefrontal cortex is decreased in the ACTH-treated rats.

    PubMed

    Li, Bingjin; Suemaru, Katsuya; Kitamura, Yoshihisa; Gomita, Yutaka; Araki, Hiroaki; Cui, Ranji

    2013-11-01

    Previous studies have shown that the antidepressive-like effect of tricyclic antidepressants is blocked by repeated treatments with adrenocorticotropic hormone (ACTH). However, little is known about the neuroanatomy underlying the mechanism of the imipramine treatment-resistant depression model. In the present study, first experimental evidence showed no significant difference of the serum imipramine concentrations between the saline and ACTH-treated rats. In further study, imipramine produced significant increases in the c-Fos expression in the medial prefrontal cortex (mPFC), the dentate gyrus of the hippocampus (DGH), and the central nucleus of the amygdala (CeA), in rats repeatedly treated with saline. The imipramine-increased c-Fos immunoreactivity was suppressed in the mPFC of rats repeatedly treated with ACTH. However, there was no significant difference in c-Fos expression in the DGH and CeA between ACTH- and saline-treated rats. These results suggest that the mPFC is maybe involved in effects of the imipramine in the ACTH-treated rats.

  19. GABAB receptor GTP-binding is decreased in the prefrontal cortex but not the hippocampus of aged rats

    PubMed Central

    McQuail, Joseph A.; Bañuelos, Cristina; LaSarge, Candi L.; Nicolle, Michelle M.; Bizon, Jennifer L.

    2011-01-01

    GABAB receptors (GABABRs) have been linked to a wide range of physiological and cognitive processes and are of interest for treating a number of neurodegenerative and psychiatric disorders. As many of these diseases are associated with advanced age, it is important to understand how the normal aging process impacts GABABR expression and signaling. Thus, we investigated GABABR expression and function in the prefrontal cortex (PFC) and hippocampus of young and aged rats characterized in a spatial learning task. Baclofen-stimulated GTP-binding and GABABR1 and GABABR2 proteins were reduced in the PFC of aged rats but these reductions were not associated with spatial learning abilities. In contrast, hippocampal GTP-binding was comparable between young and aged rats but reduced hippocampal GABABR1 expression was observed in aged rats with spatial learning impairment. These data demonstrate marked regional differences in GABABR complexes in the adult and aged brain and could have implications for both understanding the role of GABAergic processes in normal brain function and the development of putative interventions that target this system. PMID:22169202

  20. Arterial protocol including prophylactic distal perfusion catheter decreases limb ischemia complications in patients undergoing extracorporeal membrane oxygenation.

    PubMed

    Lamb, Kathleen M; DiMuzio, Paul J; Johnson, Adam; Batista, Philip; Moudgill, Neil; McCullough, Megan; Eisenberg, Joshua A; Hirose, Hitoshi; Cavarocchi, Nicholas C

    2017-04-01

    %. Limb ischemia complications from ECMO may be decreased by prophylactic placement of an antegrade DPC. Without DPC, continuous monitoring using NIRS may identify limb ischemia, which can be treated subsequently with DPC and or fasciotomy. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  1. Coronary Arterioles in Type 2 Diabetic (db/db) Mice Undergo a Distinct Pattern of Remodeling Associated with Decreased Vessel Stiffness

    PubMed Central

    Katz, Paige S.; Trask, Aaron J.; Souza-Smith, Flavia M.; Hutchinson, Kirk R.; Galantowicz, Maarten L.; Lord, Kevin C.; Stewart, James A.; Cismowski, Mary J.; Varner, Kurt J.; Lucchesi, Pamela A.

    2011-01-01

    Background Little is known about the impact of type 2 diabetes mellitus (DM) on coronary arteriole remodeling. The aim of this study was to determine the mechanisms that underlie coronary arteriole structural remodeling in type 2 diabetic (db/db) mice. Methods and Results Passive structural properties of septal coronary arterioles isolated from 12- and 16-wk-old diabetic db/db and control mice were assessed by pressure myography. Coronary arterioles from 12-wk-old db/db mice were structurally similar to age-matched controls. By 16-wks of age, coronary wall thickness was increased in db/db arterioles (p < 0.01), while luminal diameter was reduced (Control: 118±5μm; db/db: 102±4μm, p < 0.05), augmenting the wall-to-lumen ratio by 58% (Control: 5.9±0.6; db/db: 9.5±0.4, p < 0.001). Inward hypertrophic remodeling was accompanied by a 56% decrease in elastic modulus (p < 0.05, indicating decreased vessel coronary wall stiffness) and a ~30% reduction in coronary flow reserve in diabetic mice. Interestingly, aortic pulse wave velocity and femoral artery incremental modulus were increased (p < 0.05) in db/db mice, indicating macrovascular stiffness. Molecular tissue analysis revealed increased elastin-to-collagen ratio in diabetic coronaries when compared to control and a decrease in the same ratio in the diabetic aortas. Conclusions These data show that coronary arterioles isolated from type 2 diabetic mice undergo inward hypertrophic remodeling associated with decreased stiffness and increased elastin-to-collagen ratio which results in a decreased coronary flow reserve. This study suggests that coronary microvessels undergo a different pattern of remodeling from macrovessels in type 2 DM. PMID:21744279

  2. 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.

  3. Behavioral differences in an elevated plus-maze: correlation between anxiety and decreased number of GABA and benzodiazepine receptors in mouse cerebral cortex.

    PubMed

    Rägo, L; Kiivet, R A; Harro, J; Pŏld, M

    1988-06-01

    In an elevated plus-maze model of anxiety mice treated with the benzodiazepine inverse agonist DMCM (0.5-1.5 mg/kg i.p.) spent significantly less time on the open arms and showed the decreased number of open arm entries. The opposite i.e. increased time spent on the open arms and the higher number of open arm entries was registered after diazepam (1.5 mg/kg). The results are consistent with the results obtained in the other animal tests and support the idea that this procedure is suitable for detecting anxiolytic/anxiogenic effects of benzodiazepine receptor ligands. After testing of 84 mice in an elevated plus-maze substantial differences were detected between the individuals. According to the behavioral response two subgroups of animals with DMCM or diazepam like exploratory activity (as compared to the whole group data) termed as "anxious" or "non-anxious", respectively, were chosen for further binding studies. "Anxious" animals had significantly lower numbers of 3H-flunitrazepam and 3H-muscimol binding sites as compared to "non-anxious" animals in cerebral cortex but not in cerebellum. No differences in the affinity were found between the two groups studied. The results indicate that behavioral anxiety in mice is in correlation with the decreased number of GABA and benzodiazepine receptors in cerebral cortex.

  4. The significance of post-stress decrease in left ventricular ejection fraction in patients undergoing regadenoson stress gated SPECT myocardial perfusion imaging.

    PubMed

    Gomez, Javier; Golzar, Yasmeen; Fughhi, Ibtihaj; Olusanya, Adebayo; Doukky, Rami

    2017-02-08

    The significance of post-stress decrease in left ventricular ejection fraction (LVEF) with regadenoson stress gated SPECT (GSPECT) myocardial perfusion imaging (MPI) has not been studied. Consecutive patients who underwent rest/regadenoson stress GSPECT-MPI followed by coronary angiography within 6 months were analyzed. Change in LVEF by GSPECT-MPI was calculated as stress LVEF minus rest LVEF; a significant decrease was tested at 5% and 10% thresholds. In a diagnostic cohort of 793 subjects, LVEF change was not predictive of severe/extensive coronary artery disease (area under the curve, 0.50; 95% confidence interval, 0.44-0.57; P = 0.946). There was no significant difference in the rates of severe/extensive coronary artery disease in patients with or without a decrease in LVEF, irrespective of MPI findings. In an outcome cohort of the 929 subjects followed for 30 ± 16 months, post-regadenoson stress decrease in LVEF was not associated with increased risk of the composite endpoint of cardiac death or myocardial infarction or in the risk of coronary revascularization. In patients selected to undergo coronary angiography following regadenoson stress GSPECT-MPI, a decrease in LVEF after regadenoson stress is not predictive of severe/extensive CAD or adverse clinical outcomes, irrespective of MPI findings.

  5. Elevated Thyroid Peroxidase Antibody Increases Risk of Post-partum Depression by Decreasing Prefrontal Cortex BDNF and 5-HT Levels in Mice

    PubMed Central

    Zhou, Yingying; Wang, Xinyi; Zhao, Yuhang; Liu, Aihua; Zhao, Tong; Zhang, Yuanyuan; Shan, Zhongyan; Teng, Weiping

    2017-01-01

    Post-partum depression (PPD) is a common mental disease in the perinatal period that profoundly affects mothers and their offspring. Some clinical studies have found that PPD is related to thyroid peroxidase antibodies (TPOAbs); however, the mechanism underlying this relationship is unclear. Female C57BL/6 mice immunized with adenovirus encoding the cDNA of the full-length mTPO (mTPO-Ad) were used to establish the isolated TPOAb-positive mouse model in the present study. Maternal depressive-like behaviors were assessed using the forced swimming test (FST), sucrose preference test (SPT), and tail suspension test (TST) post-partum. The serum TPOAb titer was measured by enzyme-linked immunosorbent assay (ELISA) before pregnancy and post-partum. Furthermore, in the prefrontal cortex, the mRNA and protein expression levels of brain-derived neurotrophic factor (BDNF) were measured, serotonin (5-HT) levels were measured by ultra-high-performance liquid chromatography–tandem mass-spectrometry (UHPLC–MS/MS), and total thyroxine (TT4) levels were determined by ELISA. Compared with the controls, the mice immunized with mTPO-Ad displayed depressive behaviors, with a significantly lower sucrose preference (SP) at the 12-h time point and a longer immobility time in the FST and TST, which were accompanied by a lower expression of BDNF and 5-HT but no change in the TT4 concentration in the prefrontal cortex. Together, these findings suggest that elevated TPOAb may increase the risk of subsequent PPD and decrease the concentration of BDNF and 5-HT in the prefrontal cortex. PMID:28119573

  6. Decreased response of interneurons in the medial prefrontal cortex to 5-HT₁A receptor activation in the rat 6-hydroxydopamine Parkinson model.

    PubMed

    Zhang, Qiaojun; Wang, Shuang; Zhang, Lina; Zhang, Huan; Qiao, Hongfei; Niu, Xiaolin; Liu, Jian

    2014-08-01

    This study examined the response of interneurons in the medial prefrontal cortex (mPFC) to 5-HT1A receptor agonist 8-OH-DPAT and change in expression of 5-HT1A receptor on glutamate decarboxylase 67 (GAD67)-positive neurons in rats with 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (SNc). Systemic administration of 5-HT1A receptor agonist 8-OH-DPAT dose-dependently inhibited the firing rate of the interneurons at all doses tested in sham-operated rats. In 6-OHDA-lesioned rats, 8-OH-DPAT, at the same doses, also inhibited the firing rate of the interneurons, whereas the inhibition was significant only at a high cumulative dose. Furthermore, injection of 8-OH-DPAT into the mPFC inhibited the interneurons in sham-operated rats, while having no effect on firing rate of the interneurons in 6-OHDA-lesioned rats. In contrast to sham-operated rats, SNc lesion reduced the expression of 5-HT1A receptor on GAD67-positive neurons in the prelimbic cortex, a sub-region of the mPFC. Our results indicate that degeneration of the nigrostriatal pathway leads to decreased response of mPFC interneurons to 5-HT1A receptor activation, which attributes to the down-regulation of 5-HT1A receptor expression in these interneurons.

  7. 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

  8. 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.

  9. The high-affinity niacin receptor HM74A is decreased in the anterior cingulate cortex of individuals with schizophrenia.

    PubMed

    Miller, Christine L; Dulay, Jeannette R

    2008-09-05

    The pathway for de novo synthesis of the suite of niacin congeners, the kynurenine pathway, has been shown to be upregulated in prior studies of postmortem brain tissue from individuals with schizophrenia. The cause of the upregulation is unknown, but one factor may be a defect in feedback regulation via receptors responsive to niacin. A high-affinity and low-affinity receptor for niacin have been identified, HM74A and HM74, respectively. We used RT-QPCR and Western blots to quantify expression of HM74A and HM74 receptors in brain tissue obtained postmortem from patients with schizophrenia (N=12) or bipolar disorder (N=14) and from normal controls (N=14). Although the protein for the HM74 receptor was unchanged, the protein for HM74A was significantly decreased in the schizophrenia group, both when normalized to GAPDH protein or to HM74 as an internal control for degradation and gel-loading error (0.56-fold+/-0.36, p=0.016 and 0.58-fold+/-0.19 the mean control value, p=0.001, respectively). In contrast, the transcript for HM74A was significantly increased, revealing a striking dysregulation between gene transcription and final protein product. No significant differences in HM74A were found for the bipolar group relative to controls. These results are consistent with the blunted niacin flush response reported for individuals with schizophrenia and may be relevant to different rates of comorbid disease.

  10. Volitional Reduction of Anterior Cingulate Cortex Activity Produces Decreased Cue Craving in Smoking Cessation: A Preliminary Real-Time fMRI Study

    PubMed Central

    Li, Xingbao; Hartwell, Karen J.; Borckardt, Jeffery; Prisciandaro, James J.; Saladin, Michael E.; Morgan, Paul S.; Johnson, Kevin A.; LeMatty, Todd; Brady, Kathleen T.; George, Mark S.

    2012-01-01

    Numerous research groups are now using analysis of blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI) results and relaying back information about regional activity in their brains to participants in the scanner in “real time”. In this study, we explored the feasibility of self-regulation of frontal cortical activation using real time fMRI (rtfMRI) neurofeedback in nicotine-dependent cigarette smokers during exposure to smoking cues. Ten cigarette smokers were shown smoking-related visual cues in a 3 Tesla MRI scanner to induce their nicotine craving. Participants were instructed to modify their craving using rtfMRI feedback with two different approaches. In a “reduce craving” paradigm, participants were instructed to “reduce” their craving, and decrease the anterior cingulate cortex (ACC) activity. In a separate “increase resistance” paradigm, participants were asked to increase their resistance to craving and to increase middle prefrontal cortex (mPFC) activity. We found that participants were able to significantly reduce the BOLD signal in the ACC during the “reduce craving” task (p=0.028). There was a significant correlation between decreased ACC activation and reduced craving ratings during the “reduce craving” session (p=0.011). In contrast, there was no modulation of the BOLD signal in mPFC during the “increase resistance” session. These preliminary results suggest that some smokers may be able to use neurofeedback via rtfMRI to voluntarily regulate ACC activation and temporarily reduce smoking cue-induced craving. Further research is needed to determine the optimal parameters of neurofeedback rtfMRI, and whether it might eventually become a therapeutic tool for nicotine dependence. PMID:22458676

  11. Activation of the anti-inflammatory reflex blocks lipopolysaccharide-induced decrease in synaptic inhibition in the temporal cortex of the rat.

    PubMed

    Garcia-Oscos, Francisco; Peña, David; Housini, Mohammad; Cheng, Derek; Lopez, Diego; Cuevas-Olguin, Roberto; Saderi, Nadia; Salgado Delgado, Roberto; Galindo Charles, Luis; Salgado Burgos, Humberto; Rose-John, Stefan; Flores, Gonzalo; Kilgard, Michael P; Atzori, Marco

    2015-06-01

    Stress is a potential trigger for a number of neuropsychiatric conditions, including anxiety syndromes and schizophrenic psychoses. The temporal neocortex is a stress-sensitive area involved in the development of such conditions. We have recently shown that aseptic inflammation and mild electric shock shift the balance between synaptic excitation and synaptic inhibition in favor of the former in this brain area (Garcia-Oscos et al., 2012), as well as in the prefrontal cortex (Garcia-Oscos et al., 2014). Given the potential clinical importance of this phenomenon in the etiology of hyperexcitable neuropsychiatric illness, this study investigates whether inactivation of the peripheral immune system by the "anti-inflammatory reflex" would reduce the central response to aseptic inflammation. For a model of aseptic inflammation, this study used i.p. injections of the bacterial toxin lipopolysaccharide (LPS; 5 µM) and activated the anti-inflammatory reflex either pharmacologically by i.p. injections of the nicotinic α7 receptor agonist PHA543613 or physiologically through electrical stimulation of the left vagal nerve (VNS). Patch-clamp recording was used to monitor synaptic function. Recordings from LPS-injected Sprague Dawley rats show that activation of the anti-inflammatory reflex either pharmacologically or by VNS blocks or greatly reduces the LPS-induced decrease of the synaptic inhibitory-to-excitatory ratio and the saturation level of inhibitory current input-output curves. Given the ample variety of pharmacologically available α7 nicotinic receptor agonists as well as the relative safety of clinical VNS already approved by the FDA for the treatment of epilepsy and depression, our findings suggest a new therapeutic avenue in the treatment of stress-induced hyperexcitable conditions mediated by a decrease in synaptic inhibition in the temporal cortex. © 2015 Wiley Periodicals, Inc.

  12. Volitional reduction of anterior cingulate cortex activity produces decreased cue craving in smoking cessation: a preliminary real-time fMRI study.

    PubMed

    Li, Xingbao; Hartwell, Karen J; Borckardt, Jeffery; Prisciandaro, James J; Saladin, Michael E; Morgan, Paul S; Johnson, Kevin A; Lematty, Todd; Brady, Kathleen T; George, Mark S

    2013-07-01

    Numerous research groups are now using analysis of blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) results and relaying back information about regional activity in their brains to participants in the scanner in 'real time'. In this study, we explored the feasibility of self-regulation of frontal cortical activation using real-time fMRI (rtfMRI) neurofeedback in nicotine-dependent cigarette smokers during exposure to smoking cues. Ten cigarette smokers were shown smoking-related visual cues in a 3 Tesla MRI scanner to induce their nicotine craving. Participants were instructed to modify their craving using rtfMRI feedback with two different approaches. In a 'reduce craving' paradigm, participants were instructed to 'reduce' their craving, and decrease the anterior cingulate cortex (ACC) activity. In a separate 'increase resistance' paradigm, participants were asked to increase their resistance to craving and to increase middle prefrontal cortex (mPFC) activity. We found that participants were able to significantly reduce the BOLD signal in the ACC during the 'reduce craving' task (P=0.028). There was a significant correlation between decreased ACC activation and reduced craving ratings during the 'reduce craving' session (P=0.011). In contrast, there was no modulation of the BOLD signal in mPFC during the 'increase resistance' session. These preliminary results suggest that some smokers may be able to use neurofeedback via rtfMRI to voluntarily regulate ACC activation and temporarily reduce smoking cue-induced craving. Further research is needed to determine the optimal parameters of neurofeedback rtfMRI, and whether it might eventually become a therapeutic tool for nicotine dependence.

  13. Isolation rearing impairs wound healing and is associated with increased locomotion and decreased immediate early gene expression in the medial prefrontal cortex of juvenile rats.

    PubMed

    Levine, J B; Leeder, A D; Parekkadan, B; Berdichevsky, Y; Rauch, S L; Smoller, J W; Konradi, C; Berthiaume, F; Yarmush, M L

    2008-01-24

    In addition to its maladaptive effects on psychiatric function, psychosocial deprivation impairs recovery from physical illness. Previously, we found that psychosocial deprivation, modeled by isolation rearing, depressed immediate early gene (IEG) expression in the medial prefrontal cortex (mPFC) and increased locomotion in the open field test [Levine JB, Youngs RM, et al. (2007) Isolation rearing and hyperlocomotion are associated with reduced immediate early gene expression levels in the medial prefrontal cortex. Neuroscience 145(1):42-55]. In the present study, we examined whether similar changes in behavior and gene expression are associated with the maladaptive effects of psychosocial deprivation on physical injury healing. After weaning, anesthetized rats were subjected to a 20% total body surface area third degree burn injury and were subsequently either group or isolation reared. After 4 weeks of either isolation or group rearing (a period that encompasses post-wearing and early adolescence), rats were killed, and their healing and gene expression in the mPFC were assessed. Locomotion in the open field test was examined at 3 weeks post-burn injury. We found that: 1) gross wound healing was significantly impaired in isolation-reared rats compared with group-reared rats, 2) locomotion was increased and IEG expression was suppressed for isolation-reared rats during burn injury healing, 3) the decreased activity in the open field and increased IEG expression was greater for burn injury healing group-reared rats than for uninjured group-reared rats, 4) the degree of hyperactivity and IEG suppression was relatively similar between isolation-reared rats during burn injury compared with uninjured isolation-reared rats. Thus, in the mPFC, behavioral hyperactivity to novelty (the open field test) along with IEG suppression may constitute a detectable biomarker of isolation rearing during traumatic physical injury. Implications of the findings for understanding

  14. Repeated administration of Yokukansan inhibits DOI-induced head-twitch response and decreases expression of 5-hydroxytryptamine (5-HT)2A receptors in the prefrontal cortex.

    PubMed

    Egashira, Nobuaki; Iwasaki, Katsunori; Ishibashi, Ayumi; Hayakawa, Kazuhide; Okuno, Ryoko; Abe, Moe; Uchida, Naoki; Mishima, Kenichi; Takasaki, Kotaro; Nishimura, Ryoji; Oishi, Ryozo; Fujiwara, Michihiro

    2008-08-01

    Behavioral and psychological symptoms of dementia (BPSD) are commonly seen in patients with Alzheimer's disease (AD) and other forms of senile dementia. BPSD have a serious impact on the quality of life of dementia patients, as well as their caregivers. However, an effective drug therapy for BPSD has not been established. Recently, the traditional Japanese medicine Yokukansan (YKS, Yi-gan san in Chinese) has been reported to improve BPSD in a randomized, single-blind, placebo-controlled study. Moreover, abnormalities of the serotonin (5-HT) system such as 5-HT2A receptors have been reported to be associated with BPSD of AD patients. In the present study, we investigated the effect of YKS on head-twitch response induced by 2,5-dimethoxy-4-iodoamphetamine (DOI, 5 mg/kg, i.p.) in mice, a behavioral response that is mediated, in part, by 5-HT2A receptors. Acute treatment with YKS (100 and 300 mg/kg, p.o.) had no effect on the DOI-induced head-twitch response, whilst 14 days repeated treatment with YKS (300 mg/kg, p.o.) significantly inhibited this response. Moreover, repeated treatment with YKS (300 mg/kg, p.o.) decreased expression of 5-HT2A receptors in the prefrontal cortex, which is part of the circuitry mediating the head-twitch response. These findings suggest that the inhibition of DOI-induced head-twitch response by YKS may be mediated, in part, by altered expression of 5-HT2A receptors in the prefrontal cortex, which suggests the involvement of the 5-HT system in psychopharmacological effects of YKS.

  15. Pre-operative antiseptic shower and bath policy decreases the rate of S. aureus and methicillin-resistant S. aureus surgical site infections in patients undergoing joint arthroplasty.

    PubMed

    Colling, Kristin; Statz, Catherine; Glover, James; Banton, Kaysie; Beilman, Greg

    2015-04-01

    Surgical site infection (SSI) following joint arthroplasty increases length of stay, hospital cost, and leads to patient and healthcare provider dissatisfaction. Due to the presence of non-biologic implants (the prosthetic joint) in these procedures, infection is often devastating and treatment of the infection is more difficult. For this reason, prevention of SSI is of crucial importance in this population. Staphylococcus aureus colonizes the nares of approximately 30-40% of the population, is the most common pathogen causing SSI, and is associated with high morbidity and mortality rate. A pre-operative shower or bath with an antiseptic is an inexpensive and effective method of removal of these transient skin pathogens prior to the procedure and may be used to decrease SSI. We hypothesize that a preoperative antiseptic shower or bath will decrease the rate of SSI. A retrospective review was performed at two affiliated hospitals within the same system, one with a hospital-wide policy enforcing pre-operative antiseptic shower or bath and the other with no policy, with cases included from January 2010 to June 2012. International Classification of Disease-Ninth Revision-Clinical Modification (ICD-9-CM) codes and chart review were used to identify patients undergoing joint arthroplasty and to identify those with SSI. Two thousand three-hundred forty-nine arthroplasties were performed at the University of Minnesota Medical Center, a tertiary-care hospital with a pre-operative antiseptic shower or bath policy in place. An additional 1,693 procedures were performed at Fairview Ridges Hospital, a community hospital with no pre-operative policy. There was no difference in the rate of SSI between the two hospitals (1.96% vs. 1.95%; p=1.0). However, the rate of SSI caused by S. aureus was significantly decreased by pre-operative antiseptic shower/bath (17% vs. 61%; p=0.03), as was the rate of methicillin-resistant S. aureus (MRSA) infections (2% vs. 24% p=0.002). A pre

  16. 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.

  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. Systemic administration of two different anxiolytic drugs decreases local field potential theta frequency in the medial entorhinal cortex without affecting grid cell firing fields.

    PubMed

    Monaghan, Caitlin K; Chapman, G William; Hasselmo, Michael E

    2017-09-08

    Neurons coding spatial location (grid cells) are found in medial entorhinal cortex (MEC) and demonstrate increasing size of firing fields and spacing between fields (grid scale) along the dorsoventral axis. This change in grid scale correlates with differences in theta frequency, a 6-10Hz rhythm in the local field potential (LFP) and rhythmic firing of cells. A relationship between theta frequency and grid scale can be found when examining grid cells recorded in different locations along the dorsoventral axis of MEC. When describing the relationship between theta frequency and grid scale, it is important to account for the strong positive correlation between theta frequency and running speed. Plotting LFP theta frequency across running speeds dissociates two components of this relationship: slope and intercept of the linear fit. Change in theta frequency through a change in the slope component has been modeled and shown experimentally to affect grid scale, but the prediction that change in the intercept component would not affect grid scale has not been tested experimentally. This prediction about the relationship of intercept to grid scale is the primary hypothesis tested in the experiments presented here. All known anxiolytic drugs decrease hippocampal theta frequency despite their differing mechanisms of action. Specifically, anxiolytics decrease the intercept of the theta frequency-running speed relationship in the hippocampus. Here we demonstrate that anxiolytics decrease the intercept of the theta frequency-running speed relationship in the MEC, similar to hippocampus, and the decrease in frequency through this change in intercept does not affect grid scale. Copyright © 2017. Published by Elsevier Ltd.

  19. 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.

  20. Depressive-like behaviours and decreased dendritic branching in the medial prefrontal cortex of mice with tumors: A novel validated model of cancer-induced depression.

    PubMed

    Nashed, Mina G; Seidlitz, Eric P; Frey, Benicio N; Singh, Gurmit

    2015-11-01

    Depression is commonly comorbid in cancer patients and has detrimental effects on disease progression. Evidence suggests that biological mechanisms may induce the onset of cancer-induced depression (CID). The present investigation aims to establish a validated preclinical animal model of CID. Female BALB/c mice were allocated to four groups: control (n=12), chronic oral exposure to corticosterone (CORT) (n=12), CORT exposure followed by chronic low dose fluoxetine (FLX) treatment (n=12), and subcutaneous inoculation of 4T1 mammary carcinoma cells (n=13). Anhedonia was evaluated using the sucrose preference test (SPT), and behavioural despair was evaluated using the forced swim test (FST) and tail suspension test (TST). Sholl analyses were used to examine the dendritic morphology of Golgi-Cox impregnated neurons from the medial prefrontal cortex (mPFC). CORT exposure and tumor burden were both associated with decreased sucrose preference, increased FST immobility, and decreased basilar and apical dendritic branching of neurons in the mPFC. CORT-induced behavioural and dendritic morphological changes were reversible by FLX. No differences in TST immobility were observed between groups. On the secondary TST outcome measure, CORT exposure and tumor burden were associated with a trend towards decreased power of movement. CORT exposure induced a positive control model of a depressive-like state, with FLX treatment confirming the predictive validity of the model. This verified the sensitivity of behavioural and histological tests, which were used to assess the CID model. The induction of a depressive-like state in this model represents the first successfully validated animal model of CID.

  1. Decreasing ventromedial prefrontal cortex deactivation in risky decision making after simulated microgravity: effects of −6° head-down tilt bed rest

    PubMed Central

    Rao, Li-Lin; Zhou, Yuan; Liang, Zhu-Yuan; Rao, Henyi; Zheng, Rui; Sun, Yan; Tan, Cheng; Xiao, Yi; Tian, Zhi-Qiang; Chen, Xiao-Ping; Wang, Chun-Hui; Bai, Yan-Qiang; Chen, Shan-Guang; Li, Shu

    2014-01-01

    Space is characterized by risk and uncertainty. As humans play an important role in long-duration space missions, the ability to make risky decisions effectively is important for astronauts who spend extended time periods in space. The present study used the Balloon Analog Risk Task to conduct both behavioral and fMRI experiments to evaluate the effects of simulated microgravity on individuals' risk-taking behavior and the neural basis of the effect. The results showed that participants' risk-taking behavior was not affected by bed rest. However, we found that the ventromedial prefrontal cortex (VMPFC) showed less deactivation after bed rest and that the VMPFC activation in the active choice condition showed no significant difference between the win outcome and the loss outcome after bed rest, although its activation was significantly greater in the win outcome than in the loss outcome before bed rest. These results suggested that the participants showed a decreased level of value calculation after the bed rest. Our findings can contribute to a better understanding of the effect of microgravity on individual higher-level cognitive functioning. PMID:24904338

  2. Inhibiting the posterior medial prefrontal cortex by rTMS decreases the discrepancy between self and other in Theory of Mind reasoning.

    PubMed

    Schuwerk, Tobias; Schecklmann, Martin; Langguth, Berthold; Döhnel, Katrin; Sodian, Beate; Sommer, Monika

    2014-11-01

    Switching between one's own and another person's perspective is a cognitive component of Theory of Mind (ToM) reasoning that is essential for successful social interaction. Computing another's divergent belief independently from one's own perspective poses a particular challenge. Neuroimaging has demonstrated the involvement of the posterior medial prefrontal cortex (pMPFC) in establishing this perspective difference. Here, we transiently interfered with pMPFC activity by repetitive transcranial magnetic stimulation (rTMS) in a sample of young healthy adults. Reaction times of belief judgments in an adapted false belief task were measured after 1Hz rTMS applied via a double-cone coil. This procedure decreased the discrepancy in reaction times between judging another's and one's own belief, irrespective of whether they were incongruent or congruent. The current results suggest that pMPFC inhibition impaired the ability to distinguish the other's from one's own perspective and support the pMPFC's causal role in establishing perspective differences, an essential component of ToM reasoning. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Pentylenetetrazol-induced seizures are associated with Na⁺,K⁺-ATPase activity decrease and alpha subunit phosphorylation state in the mice cerebral cortex.

    PubMed

    Marquezan, Bárbara P; Funck, Vinícius R; Oliveira, Clarissa V; Pereira, Letícia M; Araújo, Stífani M; Zarzecki, Micheli S; Royes, Luiz Fernando F; Furian, Ana Flávia; Oliveira, Mauro S

    2013-08-01

    The present study aimed to investigate whether Na(+),K(+)-ATPase activity and phosphorylation state of the catalytic α subunit are altered by pentylenetetrazol (PTZ)-induced seizures. PTZ (30, 45 or 60 g/kg, i.p.) was administered to adult male Swiss mice, and Na(+),K(+)-ATPase activity and phosphorylation state were measured in the cerebral cortex 15 min after PTZ administration. Na(+),K(+)-ATPase activity significantly decreased after PTZ-induced seizures (60 mg/kg). Immunoreactivity of phosphorylated Ser943 at α subunit was increased after PTZ-induced seizures. A significant positive correlation between Na(+),K(+)-ATPase activity and latency to myoclonic jerks and generalized seizures was found. Conversely, a strong negative correlation between Ser943 phosphorylation and latency to generalized seizures was detected. Given the role of Na(+),K(+)-ATPase as a major regulator of brain excitability, Ser943 at Na(+),K(+)-ATPase α subunit may represent a potentially valuable new target for drug development for seizure disorders.

  4. Astrocytes and glutamate homoeostasis in Alzheimer's disease: a decrease in glutamine synthetase, but not in glutamate transporter-1, in the prefrontal cortex

    PubMed Central

    Kulijewicz-Nawrot, Magdalena; Syková, Eva; Chvátal, Alexander; Verkhratsky, Alexei; Rodríguez, José J.

    2013-01-01

    Astrocytes control tissue equilibrium and hence define the homoeostasis and function of the CNS (central nervous system). Being principal homoeostatic cells, astroglia are fundamental for various forms of neuropathology, including AD (Alzheimer's disease). AD is a progressive neurodegenerative disorder characterized by the loss of cognitive functions due to specific lesions in mnesic-associated regions, including the mPFC (medial prefrontal cortex). Here, we analyzed the expression of GS (glutamine synthetase) and GLT-1 (glutamate transporter-1) in astrocytes in the mPFC during the progression of AD in a triple-transgenic mouse model (3xTg-AD). GS is an astrocyte-specific enzyme, responsible for the intracellular conversion of glutamate into glutamine, whereas the removal of glutamate from the extracellular space is accomplished mainly by astroglia-specific GLT-1. We found a significant decrease in the numerical density (Nv, cells/mm3) of GS-positive astrocytes from early to middle ages (1–9 months; at the age of 1 month by 17%, 6 months by 27% and 9 months by 27% when compared with control animals) in parallel with a reduced expression of GS (determined by Western blots), which started at the age of 6 months and was sustained up to 12 months of age. We did not, however, find any changes in the expression of GLT-1, which implies an intact glutamate uptake mechanism. Our results indicate that the decrease in GS expression may underlie a gradual decline in the vital astrocyte-dependent glutamate–glutamine conversion pathway, which in turn may compromise glutamate homoeostasis, leading towards failures in synaptic connectivity with deficient cognition and memory. PMID:24059854

  5. Astrocytes and glutamate homoeostasis in Alzheimer's disease: a decrease in glutamine synthetase, but not in glutamate transporter-1, in the prefrontal cortex.

    PubMed

    Kulijewicz-Nawrot, Magdalena; Syková, Eva; Chvátal, Alexander; Verkhratsky, Alexei; Rodríguez, José J

    2013-10-07

    Astrocytes control tissue equilibrium and hence define the homoeostasis and function of the CNS (central nervous system). Being principal homoeostatic cells, astroglia are fundamental for various forms of neuropathology, including AD (Alzheimer's disease). AD is a progressive neurodegenerative disorder characterized by the loss of cognitive functions due to specific lesions in mnesic-associated regions, including the mPFC (medial prefrontal cortex). Here, we analyzed the expression of GS (glutamine synthetase) and GLT-1 (glutamate transporter-1) in astrocytes in the mPFC during the progression of AD in a triple-transgenic mouse model (3xTg-AD). GS is an astrocyte-specific enzyme, responsible for the intracellular conversion of glutamate into glutamine, whereas the removal of glutamate from the extracellular space is accomplished mainly by astroglia-specific GLT-1. We found a significant decrease in the numerical density (Nv, cells/mm3) of GS-positive astrocytes from early to middle ages (1-9 months; at the age of 1 month by 17%, 6 months by 27% and 9 months by 27% when compared with control animals) in parallel with a reduced expression of GS (determined by Western blots), which started at the age of 6 months and was sustained up to 12 months of age. We did not, however, find any changes in the expression of GLT-1, which implies an intact glutamate uptake mechanism. Our results indicate that the decrease in GS expression may underlie a gradual decline in the vital astrocyte-dependent glutamate-glutamine conversion pathway, which in turn may compromise glutamate homoeostasis, leading towards failures in synaptic connectivity with deficient cognition and memory.

  6. Decreased dendritic spine density of neurons of the prefrontal cortex and nucleus accumbens and enhanced amphetamine sensitivity in postpubertal rats after a neonatal amygdala lesion.

    PubMed

    Solis, Oscar; Vázquez-Roque, Rubén Antonio; Camacho-Abrego, Israel; Gamboa, Citlalli; De La Cruz, Fidel; Zamudio, Sergio; Flores, Gonzalo

    2009-12-01

    A neonatal basolateral-amygdala (nBLA) lesion in rats could be a potential animal model to study the early neurodevelopmental abnormalities associated with the behavioral and morphological brain changes observed in schizophrenia. Morphological alterations in pyramidal neurons from the prefrontal cortex (PFC) have been observed in postmortem schizophrenic brains, mainly because of decreased dendritic arbor and spine density. We assessed the effects of nBLA-lesion on the dendritic morphology of neurons from the PFC and the nucleus accumbens (NAcc) in rats. nBLA lesions were made on postnatal day 7 (PD7), and later, the dendritic morphology was studied by the Golgi-Cox stain procedure followed by Sholl analysis at PD35 (prepubertal) and PD60 (adult) ages. We also evaluated the effects of the nBLA-lesion on locomotor activity caused by a novel environment, apomorphine, and amphetamine. Adult animals with nBLA lesions showed a decreased spine density in pyramidal neurons from the PFC and in medium spiny cells from the NAcc. An increased locomotion in a novel environment and in amphetamine-treated adult animals with an nBLA-lesion was observed. Our results indicate that nBLA-lesion alters the neuronal dendrite morphology of the NAcc and PFC, suggesting a disconnection between these limbic structures. The locomotion paradigms support the idea that dopaminergic transmission is altered in the nBLA lesion model. This could help to understand the consequences of an earlier amygdala dysfunction in schizophrenia. (c) 2009 Wiley-Liss, Inc.

  7. Elevated oxidative stress and decreased antioxidant function in the human hippocampus and frontal cortex with increasing age: implications for neurodegeneration in Alzheimer's disease.

    PubMed

    Venkateshappa, C; Harish, G; Mahadevan, Anita; Srinivas Bharath, M M; Shankar, S K

    2012-08-01

    Oxidative stress and mitochondrial damage are implicated in the evolution of neurodegenerative diseases. Increased oxidative damage in specific brain regions during aging might render the brain susceptible to degeneration. Previously, we demonstrated increased oxidative damage and lowered antioxidant function in substantia nigra during aging making it vulnerable to degeneration associated with Parkinson's disease. To understand whether aging contributes to the vulnerability of brain regions in Alzheimer's disease, we assessed the oxidant and antioxidant markers, glutathione (GSH) metabolic enzymes, glial fibrillary acidic protein (GFAP) expression and mitochondrial complex I (CI) activity in hippocampus (HC) and frontal cortex (FC) compared with cerebellum (CB) in human brains with increasing age (0.01-80 years). We observed significant increase in protein oxidation (HC: p = 0.01; FC: p = 0.0002) and protein nitration (HC: p = 0.001; FC: p = 0.02) and increased GFAP expression (HC: p = 0.03; FC: p = 0.001) with a decreasing trend in CI activity in HC and FC compared to CB with increasing age. These changes were associated with a decrease in antioxidant enzyme activities, such as superoxide dismutase (HC: p = 0.005), catalase (HC: p = 0.02), thioredoxin reductase (FC: p = 0.04), GSH reductase (GR) (HC: p = 0.005), glutathione-s-transferase (HC: p = 0.0001; FC: p = 0.03) and GSH (HC: p = 0.01) with age. However, these parameters were relatively unaltered in CB. We suggest that the regions HC and FC are subjected to widespread oxidative stress, loss of antioxidant function and enhanced GFAP expression during aging which might make them more susceptible to deranged physiology and selective neuronal degeneration.

  8. Cyclic AMP response element-binding protein in post-mortem brain of teenage suicide victims: specific decrease in the prefrontal cortex but not the hippocampus.

    PubMed

    Pandey, Ghanshyam N; Dwivedi, Yogesh; Ren, Xinguo; Rizavi, Hooriyah S; Roberts, Rosalinda C; Conley, Robert R

    2007-10-01

    Abnormalities in both adenylyl cyclase (AC) and phosphoinositide (PI) signalling systems have been observed in the post-mortem brain of suicide victims. Cyclic AMP response element-binding protein (CREB) is a transcription factor that is activated by phosphorylating enzymes such as protein kinase A (PKA) and protein kinase C (PKC), which suggests that both AC and PI signalling systems converge at the level of CREB. CREB is involved in the transcription of many neuronally expressed genes that have been implicated in the pathophysiology of depression and suicide. Since we observed abnormalities of both PKA and PKC in the post-mortem brain of teenage suicide victims, we examined if these abnormalities are also associated with abnormalities of CREB, which is activated by these phosphorylating enzymes. We determined CRE-DNA binding using the gel shift assay, as well as protein expression of CREB using the Western blot technique, and the mRNA expression of CREB using a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) technique in the prefrontal cortex (PFC), and hippocampus obtained from 17 teenage suicide victims and 17 matched normal control subjects. We observed that the CRE-DNA binding and the protein expression of CREB were significantly decreased in the PFC of teenage suicide victims compared with controls. There was also a significant decrease in mRNA expression of CREB in the PFC of teenage suicide victims compared with control subjects. However, there were no significant differences in CRE-DNA binding or the protein and mRNA expression of CREB in the hippocampus of teenage suicide victims compared with control subjects. These results suggest that the abnormalities of PKA, and of PKC, observed in teenage suicide victims are also associated with abnormalities of the transcription factor CREB, and that this may also cause alterations of important neuronally expressed genes, and provide further support of the signal transduction of abnormalities

  9. Decreased pretreatment lymphocyte/monocyte ratio is associated with poor prognosis in stage Ib1–IIa cervical cancer patients who undergo radical surgery

    PubMed Central

    Chen, Liang; Zhang, Fang; Sheng, Xiu-gui; Zhang, Shi-qian

    2015-01-01

    Background Recently, pretreatment monocyte counts and the lymphocyte/monocyte ratio (LMR) have been proven to be significantly associated with the clinical outcomes of several types of cancer. In this study, we analyzed the prognostic significance of the LMR in stage Ib1–IIa cervical cancer patients who underwent a radical operation. Methods A total of 485 patients with stage Ib1–IIa cervical cancer were included in this retrospective study. We evaluated the prognostic values of the absolute lymphocyte count, absolute monocyte count, and LMR by applying receiver operating characteristic curves. Kaplan–Meier curves and multivariate Cox proportional analyses were used to determine the recurrence-free survival (RFS) and overall survival (OS). Results The area under the curve was 0.640 for the RFS and 0.647 for the OS using the LMR. In the univariate analysis, an elevated preoperative LMR was significantly associated with an increased RFS (hazard ratio [HR], 0.373; 95% confidence interval [CI]: 0.247–0.563; P<0.001), and this result remained significant in the multivariate analysis (HR, 0.439; 95% CI: 0.279–0.693; P<0.001). In the univariate analysis, an elevated LMR was also significantly associated with an increased OS (HR, 0.381; 95% CI: 0.233–0.622; P<0.001), and the significance persisted in the multivariate analysis (HR, 0.417; 95% CI: 0.244–0.714; P=0.001). Conclusion A decreased pretreatment LMR is associated with a poor prognosis in stage Ib1–IIa cervical cancer patients who undergo a radical operation. A prospective study is warranted for further validation of our findings. PMID:26089685

  10. Chronic unpredictable mild stress decreases BDNF and NGF levels and Na(+),K(+)-ATPase activity in the hippocampus and prefrontal cortex of mice: antidepressant effect of chrysin.

    PubMed

    Filho, C B; Jesse, C R; Donato, F; Giacomeli, R; Del Fabbro, L; da Silva Antunes, M; de Gomes, M G; Goes, A T R; Boeira, S P; Prigol, M; Souza, L C

    2015-03-19

    Our working hypothesis is that brain neurotrophins and brain Na(+),K(+)-ATPase may be strongly associated with the occurrence of depression in animals subjected to chronic unpredictable mild stress (CUMS). Still, we believe that chrysin, a natural and bioactive flavonoid found in honey and some plants, can provide satisfactory effects on antidepressant therapy. Thus, we aimed to evaluate the effect of CUMS on brain-derived neurotropic factor (BDNF) and nerve growth factor (NGF) levels as well as the Na(+),K(+)-ATPase activity in the hippocampus and prefrontal cortex of female mice. We also aimed to examine the effect of a 28-day oral treatment with chrysin (5 or 20mg/kg) in female mice subjected to CUMS, comparing to the effect of fluoxetine. Results showed that CUMS applied for 28days induced a decrease in BDNF and NGF levels as well as in the Na(+),K(+)-ATPase activity. CUMS also promoted a depressive status in the swimming forced test (FST), in the sucrose preference test, and in corticosterone levels. Chrysin (20mg/kg) and fluoxetine also occasioned the up-regulation of BDNF and NGF levels in non-stressed mice and in mice subjected to CUMS. CUMS decreased non-protein thiol (NPSH) levels and increased reactive oxygen species (ROS) levels. In response to these changes, the glutathione reductase (GR), glutathione peroxidase (GPx) and catalase (CAT) activities were increased in mice exposed to CUMS. Chrysin and fluoxetine treatments protected against all these alterations, suggesting the involvement of the antioxidant function in the antidepressant effect of chrysin and fluoxetine. In conclusion, CUMS decreased BDNF and NGF levels as well as the Na(+),K(+)-ATPase activity in mice. Chrysin presented antidepressant effect in mice on behavioral, neurotrophic and biochemistry parameters equivalent to fluoxetine. Furthermore, we suggest that the up-regulation of BDNF and NGF levels is a mechanism possibly involved in the antidepressant effect of chrysin in mice

  11. Age-related spatial cognitive impairment is correlated with a decrease in ChAT in the cerebral cortex, hippocampus and forebrain of SAMP8 mice.

    PubMed

    Wang, Feng; Chen, Hong; Sun, Xiaojiang

    2009-05-01

    At present, the mechanisms underlying cognitive disorders remain unclear. The senescence-accelerated mice (SAM) prone/8 (P8) has been proposed as a useful model for the study of aging, and SAM resistant/1 (R1) is its control as a normal aging strain. The purpose of this study was to investigate choline acetyltransferase (ChAT) expression in SAM brain. The age-related decline of learning and memory ability in P8 mice (4, 8 and 12 months old, n=10 for each group) was proved in Morris water maze test (MWM). After the behavioral test, protein and mRNA levels of ChAT were determined in the cerebral cortex, hippocampus and forebrain by means of immunostaining, Western blotting, and real time quantitative PCR (QPCR). Comparing with 4-month-old P8 and R1, 8- and 12-month-old P8 showed age-related cognitive impairment in MWM test. The latencies of the 4-month-old P8 in a hidden platform trial were significantly shorter, and the retention time was significantly longer than that of the older P8 groups. In addition, significantly low level of ChAT protein was observed in older P8 groups. Comparing with the 4-month-old P8, ChAT mRNA in the 12-month-old P8 declined significantly in all three regions of P8 brain. Pearson correlation test showed that the latencies in the MWM were positively correlated with the level of ChAT in P8. Such phenomenon could not be detected in normal aging R1 mice. These findings suggest that the decrease of ChAT in P8 mice was responsible for the age-related learning and memory impairments in some sense.

  12. Morphological and physiological studies of rat kidney cortex slices undergoing isosmotic swelling and its reversal: a possible mechanism for ouabain-resistant control of cell volume.

    PubMed

    Russo, M A; Ernst, S A; Kapoor, S C; van Rossum, G D

    1985-01-01

    Slices of rat kidney cortex were induced to swell by preincubation at 1 degree C in an isotonic Ringer's solution, and their capacity to reverse swelling, by net extrusion of cellular water, was studied during subsequent incubation at 25 degrees C. The recovery from swelling was prevented by the respiratory inhibitor, antimycin A. On the other hand, extrusion of water was little affected by ouabain. The extrusion of water continuing in the presence of ouabain (but not that in its absence) was significantly reduced when furosemide was added or when medium Cl- was replaced by NO-3 or I-. There was substantial variability in the morphological appearance of cells within the cortical slices. Different segments of the nephron showed different structural changes during swelling and its reversal, the proximal tubules being most markedly affected. Proximal tubular cells of swollen slices showed disorganization of brush borders and expansion of their apical surfaces, and contained vesicles in their apical cytoplasm. Upon recovery at 25 degrees C, the apical portions of these cells showed reversal of the expansion, but some apical vesicles remained. These vesicles were much more numerous after recovery in the presence of ouabain, but they were much reduced in numbers, or totally absent, when recovery took place in the presence of furosemide or absence of Cl-, with or without ouabain. The vesicles seen in the presence of ouabain alone appeared to fuse with each other and with infoldings of the basolateral plasma membrane. Rather similar results were obtained with distal tubular cells in the slices. We suggest that volume regulation in the proximal and distal tubular cells proceeds by way of two mechanisms. The first consists of extrusion of water coupled to the ouabain-sensitive transport of Na+ and K+. The other proceeds by way of an ouabain-resistant entry of water into apical cytoplasmic vesicles, following furosemide-sensitive movements of Cl- and Na+; the vesicles then

  13. Prasugrel Results in Higher Decrease in High-Sensitivity C-Reactive Protein Level in Patients Undergoing Percutaneous Coronary Intervention Comparing to Clopidogrel

    PubMed Central

    Hajsadeghi, Shokoufeh; Chitsazan, Mandana; Chitsazan, Mitra; Salehi, Negar; Amin, Ahmad; Bidokhti, Arash Amin; Babaali, Nima; Bordbar, Armin; Hejrati, Maral; Moghadami, Samar

    2016-01-01

    OBJECTIVES A growing body of clinical and laboratory evidence indicates that inflammation plays a crucial role in atherosclerosis. In the present study, we compared the effects of clopidogrel and prasugrel on high-sensitivity C-reactive protein (hs-CRP) in patients undergoing percutaneous coronary intervention (PCI). METHODS The present randomized, double-blind clinical trial included 120 patients who underwent PCI. Eligible patients were randomly assigned 2:1 to one of the two groups: 80 patients in the first group received clopidogrel (Plavix®; loading dose and maintenance dose of 300 and 75 mg daily, respectively) and 40 patients in the second group received prasugrel (Effient®; loading dose and maintenance dose of 60 and 10 mg, respectively) for 12 weeks. The hs-CRP levels between baseline and 12th week were compared. RESULTS Of the 120 patients, 69 patients (57.5%) were male. Pretreatment hs-CRP level was statistically comparable in clopidogrel (median, 15.10 mg/dL; interquartile range [IQR], 9.62–23.75 mg/dL) and prasugrel groups (median, 18 mg/dL; IQR, 14.25–22 mg/dL; P = 0.06). Patients taking clopidogrel showed a significant reduction in hs-CRP level compared with the baseline values (P < 0.001). Prasugrel administration also resulted in a significant reduction in hs-CRP level (P < 0.001). A significant 73% overall reduction in the hs-CRP level was seen with prasugrel compared with 39% overall reduction in hs-CRP level with clopidogrel (P = 0.002). CONCLUSION Prasugrel seems to be superior to clopidogrel in the reduction of hs-CRP in patients undergoing PCI. PMID:27597810

  14. 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.

  15. Proteomic profile of primary isolated rat mesangial cells in high-glucose culture condition and decreased expression of PSMA6 in renal cortex of diabetic rats.

    PubMed

    Li, Zhiguo; Zhang, Haojun; Dong, Xi; Burczynski, Frank J; Choy, Patrick; Yang, Fang; Liu, Hui; Li, Ping; Gong, Yuewen

    2010-08-01

    Diabetic nephropathy (DN) is one of the most important complications of diabetic patients and is characterized histologically by an accumulation of extracellular matrix (ECM) protein in the glomerular mesangium. Therefore, mesangial cells likely play an important role in the development of diabetic nephropathy. Here, we employed proteomic techniques to investigate the protein profile of rat mesangial cells under high-glucose culture conditions. Primary isolated rat glomerular mesangial cells were cultured under different concentrations of glucose (5.4 mmol.L-1 for normal control and 30 mmol.L-1 for high glucose) for 0, 8, 16, and 72 h, as well as for 25 days. Cellular total proteins were isolated from these cells and employed for two-dimensional gel electrophoresis (2-DE). Differentially expressed proteins were identified by matrix-assisted laser desorption - ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and some of these proteins were documented in rat models of diabetes by Western blot. Rat mesangial cells were successfully isolated in the laboratory and their proliferation rates were significantly inhibited by high glucose. Two-dimensional gel electrophoresis analyses revealed 28 differentially expressed protein spots between the normal and high-glucose groups. After MALDI-TOF-MS analysis, all 28 protein spots were successfully identified with the peptide mass fingerprint (PMF) method. Representatively, SOD1, PCBP1 and PSMA6 were validated by Western blot analysis following protein extractions from the normal and high-glucose groups. Abundance of these proteins was consistent with that found in 2-DE. Moreover, expression of SOD1, PCBP1, and PSMA6 in renal cortex was further examined in two rat models of diabetes (streptozotocin-induced and spontaneous OLETF diabetic models). Abundance of SOD1 and PCBP1 proteins did not show any significant difference between normal control and diabetic rats. However, abundance of the PSMA6 protein was significantly

  16. The head-down tilt position decreases vasopressor requirement during hypotension following induction of anaesthesia in patients undergoing elective coronary artery bypass graft and valvular heart surgeries.

    PubMed

    Lim, Tae wan; Kim, Hyun J; Lee, Jung-Man; Kim, Jun H; Hong, Deok M; Jeon, Yunseok; Roh, Young-Jin; Lim, Young J; Bahk, Jae-Hyon

    2011-01-01

    Previous studies have failed to demonstrate that the head-down tilt position confers benefits in hypovolaemic hypotensive patients. The aim of this study was to evaluate the haemodynamic effect and vasopressor use by this position in hypotensive patients after the induction of general anaesthesia. This prospective randomised study involved 98 patients scheduled for elective cardiac surgery and 40 patients (40.1%) developed hypotension after anaesthesia induction. Upon occurrence of hypotension, patients were randomly allocated to the supine (n = 19) or head-down tilt (n = 21) groups (15° head-down tilt position). Blood pressure, heart rate, cardiac index and stroke volume index were recorded at 1-min interval for 10 min from the occurrence of hypotension. Vasopressors were administered to treat hypotension in both groups. No haemodynamic difference was observed between the supine and head-down tilt groups except for SBP changes from baseline at 1 min (-3.98 ± 6.31 vs. 1.84 ± 8.25%, P = 0.004) and 2 min (1.51 ± 14.34 vs. 9.37 ± 10.57%, P = 0.032). The number of vasopressor administrations and percentage of the patients requiring vasopressors in the supine group were greater than that in the head-down tilt group [median 1 (range 1-5) vs. median 0 (range 0-2), P = 0.002, 19/19 (100%) vs. 10/21 (47.6%), P < 0.001]. The head-down tilt position in hypotensive patients following anaesthesia induction reduced vasopressor requirement by almost one third. Minimal haemodynamic effect may be caused by different vasopressor administrations. This result suggests that the head-down tilt position may enable more stable anaesthesia induction in patients undergoing elective coronary artery bypass graft or valvular heart surgeries.

  17. The 5-HT1A/1B-receptor agonist eltoprazine increases both catecholamine release in the prefrontal cortex and dopamine release in the nucleus accumbens and decreases motivation for reward and "waiting" impulsivity, but increases "stopping" impulsivity.

    PubMed

    Korte, S Mechiel; Prins, Jolanda; Van den Bergh, Filip S; Oosting, Ronald S; Dupree, Rudy; Korte-Bouws, Gerdien A H; Westphal, Koen G C; Olivier, Berend; Denys, Damiaan A; Garland, Alexis; Güntürkün, Onur

    2017-01-05

    The 5-HT1A/1B-receptor agonist eltoprazine has a behavioral drug signature that resembles that of a variety of psychostimulant drugs, despite the differences in receptor binding profile. These psychostimulants are effective in treating impulsivity disorders, most likely because they increase norepinephrine (NE) and dopamine (DA) levels in the prefrontal cortex. Both amphetamine and methylphenidate, however, also increase dopamine levels in the nucleus accumbens (NAc), which has a significant role in motivation, pleasure, and reward. How eltoprazine affects monoamine release in the medial prefrontal cortex (mPFC), the orbitofrontal cortex (OFC), and the NAc is unknown. It is also unknown whether eltoprazine affects different forms of impulsivity and brain reward mechanisms. Therefore, in the present study, we investigate the effects of eltoprazine in rats in the following sequence: 1) the activity of the monoaminergic systems using in vivo microdialysis, 2) motivation for reward measured using the intracranial self-stimulation (ICSS) procedure, and finally, 3) "waiting" impulsivity in the delay-aversion task, and the "stopping" impulsivity in the stop-signal task. The microdialysis studies clearly showed that eltoprazine increased DA and NE release in both the mPFC and OFC, but only increased DA concentration in the NAc. In contrast, eltoprazine decreased 5-HT release in the mPFC and NAc (undetectable in the OFC). Remarkably, eltoprazine decreased impulsive choice, but increased impulsive action. Furthermore, brain stimulation was less rewarding following eltoprazine treatment. These results further support the long-standing hypothesis that "waiting" and "stopping" impulsivity are regulated by distinct neural circuits, because 5-HT1A/1B-receptor activation decreases impulsive choice, but increases impulsive action. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Effectiveness of a nursing intervention in decreasing the anxiety levels of family members of patients undergoing cardiac surgery: a randomized clinical trial

    PubMed Central

    Hamester, Letícia; de Souza, Emiliane Nogueira; Cielo, Cibele; Moraes, Maria Antonieta; Pellanda, Lúcia Campos

    2016-01-01

    ABSTRACT Objective: to verify the effectiveness of nursing orientation provided to families of patients in the immediate post-operative following cardiac surgery before the first visit to the post-anesthesia care unit, in decreasing anxiety levels, compared to the unit's routine orientation. Method: open randomized clinical trial addressing family members in the waiting room before the first visit in the immediate post-operative period. The family members assigned to the intervention group received audiovisual orientation concerning the patients' conditions at the time and the control group received the unit's routine orientation. Outcome anxiety was assessed using the STAI-State. Results: 210 individuals were included, 105 in each group, aged 46.4 years old on average (±14.5); 69% were female and 41% were the patients' children. The mean score obtained on the anxiety assessment in the intervention group was 41.3±8.6, while the control group scored 50.6±9.4 (p<0.001). Conclusion: a nursing intervention focused on providing guidance to families before their first visit to patients in the immediate post-operative period of cardiac surgery helps to decrease the levels of anxiety of companions, making them feel better prepared for the moment. ReBEC (Brazilian Clinical Trials Registry) and The Universal Trial Number (UTN), No. U1111-1145-6172. PMID:27533263

  19. Hypergravity exposure decreases gamma-aminobutyric acid immunoreactivity in axon terminals contacting pyramidal cells in the rat somatosensory cortex: a quantitative immunocytochemical image analysis

    NASA Technical Reports Server (NTRS)

    D'Amelio, F.; Wu, L. C.; Fox, R. A.; Daunton, N. G.; Corcoran, M. L.; Polyakov, I.

    1998-01-01

    Quantitative evaluation of gamma-aminobutyric acid immunoreactivity (GABA-IR) in the hindlimb representation of the rat somatosensory cortex after 14 days of exposure to hypergravity (hyper-G) was conducted by using computer-assisted image processing. The area of GABA-IR axosomatic terminals apposed to pyramidal cells of cortical layer V was reduced in rats exposed to hyper-G compared with control rats, which were exposed either to rotation alone or to vivarium conditions. Based on previous immunocytochemical and behavioral studies, we suggest that this reduction is due to changes in sensory feedback information from muscle receptors. Consequently, priorities for muscle recruitment are altered at the cortical level, and a new pattern of muscle activity is thus generated. It is proposed that the reduction observed in GABA-IR of the terminal area around pyramidal neurons is the immunocytochemical expression of changes in the activity of GABAergic cells that participate in reprogramming motor outputs to achieve effective movement control in response to alterations in the afferent information.

  20. Hypergravity exposure decreases gamma-aminobutyric acid immunoreactivity in axon terminals contacting pyramidal cells in the rat somatosensory cortex: a quantitative immunocytochemical image analysis

    NASA Technical Reports Server (NTRS)

    D'Amelio, F.; Wu, L. C.; Fox, R. A.; Daunton, N. G.; Corcoran, M. L.; Polyakov, I.

    1998-01-01

    Quantitative evaluation of gamma-aminobutyric acid immunoreactivity (GABA-IR) in the hindlimb representation of the rat somatosensory cortex after 14 days of exposure to hypergravity (hyper-G) was conducted by using computer-assisted image processing. The area of GABA-IR axosomatic terminals apposed to pyramidal cells of cortical layer V was reduced in rats exposed to hyper-G compared with control rats, which were exposed either to rotation alone or to vivarium conditions. Based on previous immunocytochemical and behavioral studies, we suggest that this reduction is due to changes in sensory feedback information from muscle receptors. Consequently, priorities for muscle recruitment are altered at the cortical level, and a new pattern of muscle activity is thus generated. It is proposed that the reduction observed in GABA-IR of the terminal area around pyramidal neurons is the immunocytochemical expression of changes in the activity of GABAergic cells that participate in reprogramming motor outputs to achieve effective movement control in response to alterations in the afferent information.

  1. Decreased expression of granulocyte-macrophage colony-stimulating factor is associated with adverse clinical outcome in patients with gastric cancer undergoing gastrectomy.

    PubMed

    Liu, Hao; Lin, Chao; Shen, Zhenbin; Zhang, Heng; He, Hongyong; Li, He; Qin, Jing; Qin, Xinyu; Xu, Jiejie; Sun, Yihong

    2017-10-01

    Previous studies have revealed the clinical significance of tumor-associated macrophages (TAMs) in gastric cancer, whereas the role of the cytokines that orchestrate TAM polarization in gastric cancer remains elusive. The present study aimed to evaluate the prognostic value of granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in patients with gastric cancer. Intratumoral GM-CSF expression was investigated by immunohistochemical staining in 408 retrospectively enrolled patients. Kaplan-Meier analysis and Cox regression models were used to evaluate the prognostic value of GM-CSF expression. Predictive nomograms were generated to predict the overall survival and disease-free survival rates of the patients. Decreased intratumoral GM-CSF expression was identified, and indicated a poorer clinical outcome for patients with gastric cancer, particularly in advanced stages. Intratumoral GM-CSF expression may provide an additional risk stratification for the prognosis of patients with gastric cancer based on the Tumor-Node-Metastasis (TNM) staging system. Cox multivariate analysis identified GM-CSF expression as an independent prognostic factor for overall survival and disease-free survival time. The generated nomograms performed well in predicting the 3-and 5-year clinical outcome of patients with gastric cancer. In conclusion, GM-CSF is a potential independent prognostic indicator for patients with gastric cancer, which may be integrated with TNM staging systems to improve the predictive accuracy for clinical outcome, particularly in advanced tumors.

  2. Phase II Randomized Trial of Negative-Pressure Wound Therapy to Decrease Surgical Site Infection in Patients Undergoing Laparotomy for Gastrointestinal, Pancreatic, and Peritoneal Surface Malignancies

    PubMed Central

    Shen, Perry; Blackham, Aaron U; Lewis, Stacey; Clark, Clancy J; Howerton, Russell; Mogal, Harveshp D; Dodson, Rebecca M; Russell, Gregory B; Levine, Edward A

    2017-01-01

    BACKGROUND Surgical site infections (SSIs) remain a major source of morbidity and cost after resection of intra-abdominal malignancies. Negative-pressure wound therapy (NPWT) has been reported to significantly reduce SSIs when applied to the closed laparotomy incision. This article reports the results of a randomized clinical trial examining the effect of NPWT on SSI rates in surgical oncology patients with increased risk for infectious complications. STUDY DESIGN From 2012 to 2016, two hundred and sixty-five patients who underwent open resection of intra-abdominal neoplasms were stratified into 3 groups: gastrointestinal (n = 57), pancreas (n = 73), or peritoneal surface (n = 135) malignancy. They were randomized to receive NPWT or standard surgical dressing (SSD) applied to the incision from postoperative days 1 through 4. Primary outcomes of combined incisional (superficial and deep) SSI rates were assessed up to 30 days after surgery. RESULTS There were no significant differences in superficial SSIs (12.8% vs 12.9%; p > 0.99) or deep SSI (3.0% vs 3.0%; p > 0.99) rates between the SSD and NPWT groups, respectively. When stratified by type of surgery, there were still no differences in combined incisional SSI rates for gastrointestinal (25% vs 24%; p > 0.99), pancreas (22% vs 22%; p > 0.99), and peritoneal surface malignancy (9% vs 9%; p > 0.99) patients. When performing univariate and multivariate logistic regression analysis of demographic and operative factors for the development of combined incisional SSI, the only independent predictors were preoperative albumin (p = 0.0031) and type of operation (p = 0.018). CONCLUSIONS Use of NPWT did not significantly reduce incisional SSI rates in patients having open resection of gastrointestinal, pancreatic, or peritoneal surface malignancies. Based on these results, at this time NPWT cannot be recommended as a therapeutic intervention to decrease infectious complications in these patient populations. PMID:28088597

  3. Glucocorticoid regulates TrkB protein levels via c-Cbl dependent ubiquitination: a decrease in c-Cbl mRNA in the prefrontal cortex of suicide subjects.

    PubMed

    Pandya, Chirayu; Kutiyanawalla, Ammar; Turecki, Gustavo; Pillai, Anilkumar

    2014-07-01

    Brain derived neurotrophic factor (BDNF) signaling through its receptor TrkB plays a crucial role in neurodevelopment and plasticity. Stress and glucocorticoids have been shown to alter TrkB signaling in neurons, and defects in TrkB expression have been reported in the prefrontal cortex of suicide subjects. Glucocorticoid treatment has been shown to induce deleterious effects on the neuronal maturation. However, the mechanisms involved in the regulation of TrkB by glucocorticoid during neurodevelopment are not clear. Here we show that acute corticosterone exposure induced posttranslational upregulation of TrkB in primary cortical neurons (days in vitro 4, DIV4), which was blocked by the proteasome inhibitors. Acute corticosterone-induced increase in TrkB protein levels was dependent on glucocorticoid receptor (GR). At the cellular level, ubiquitin E3 ligase c-Cbl mediates TrkB stabilization and corticosterone-induced TrkB levels. Moreover, the tyrosine kinase binding domain in c-Cbl plays a critical role in corticosterone-induced TrkB levels. Chronic treatment of neurons with corticosterone induced significant decreases in both TrkB and c-Cbl protein levels. Acute corticosterone treatment failed to induce any significant change in TrkB and c-Cbl protein levels in mature neurons (DIV 12), where as chronic corticosterone exposure reduced TrkB levels. Under an in vivo condition, chronic corticosterone exposure induced down-regulation of c-Cbl in mouse frontal cortex and hippocampus. Importantly, we demonstrate for the first time a significant decrease in c-Cbl mRNA levels in the prefrontal cortex of suicide subjects indicating the possible role of c-Cbl in the pathophysiology of suicidal behavior. Thus, ubiquitin-proteasome-mediated TrkB regulation may be an important mechanism for improving BDNF signaling and maintaining neuroplasticity in stress-related neuropsychiatric disorders.

  4. Premonitory urges are associated with decreased grey matter thickness within the insula and sensorimotor cortex in young people with Tourette syndrome.

    PubMed

    Draper, Amelia; Jackson, Georgina M; Morgan, Paul S; Jackson, Stephen R

    2016-03-01

    Tourette syndrome (TS) is a neurological disorder characterized by vocal and motor tics and is associated with cortical-striatal-thalamic-cortical circuit (CSTC) dysfunction and hyperexcitability of cortical limbic and motor regions, which are thought to lead to the occurrence of tics. Importantly, individuals with TS often report that their tics are preceded by 'premonitory sensory phenomena' (PSP) that are described as uncomfortable cognitive or bodily sensations that precede the execution of a tic, and are experienced as a strong urge for motor discharge. While the precise role played by PSP in the occurrence of tics is controversial, PSP are nonetheless of considerable theoretical and clinical importance in TS, not least because they form the core component in many of the behavioural therapies that are currently used in the treatment of tic disorders. In this study, we investigated the brain structure correlates of PSP. Specifically, we conducted a whole-brain analysis of cortical (grey matter) thickness in 29 children and young adults with TS and investigated the association between grey matter thickness and PSP. We demonstrate for the first time that PSP are inversely associated with grey matter thickness measurements within the insula and sensorimotor cortex. We also demonstrate that grey matter thickness is significantly reduced in these areas in individuals with TS relative to a closely age- and gender-matched group of typically developing individuals and that PSP ratings are significantly correlated with tic severity. © 2015 The Authors. Journal of Neuropsychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.

  5. Individual vulnerability to escalated aggressive behavior by a low dose of alcohol: decreased serotonin receptor mRNA in the prefrontal cortex of male mice.

    PubMed

    Chiavegatto, S; Quadros, I M H; Ambar, G; Miczek, K A

    2010-02-01

    Low to moderate doses of alcohol consumption induce heightened aggressive behavior in some, but not all individuals. Individual vulnerability for this nonadaptive behavior may be determined by an interaction of genetic and environmental factors with the sensitivity of alcohol's effects on brain and behavior. We used a previously established protocol for alcohol oral self-administration and characterized alcohol-heightened aggressive (AHA) mice as compared with alcohol non-heightened (ANA) counterparts. A week later, we quantified mRNA steady state levels of several candidate genes in the serotonin [5-hydroxytryptamine (5-HT)] system in different brain areas. We report a regionally selective and significant reduction of all 5-HT receptor subtype transcripts, except for 5-HT(3), in the prefrontal cortex of AHA mice. Comparable gene expression profile was previously observed in aggressive mice induced by social isolation or by an anabolic androgenic steroid. Additional change in the 5-HT(1B) receptor transcripts was seen in the amygdala and hypothalamus of AHA mice. In both these areas, 5-HT(1B) mRNA was elevated when compared with ANA mice. In the hypothalamus, AHA mice also showed increased transcripts for 5-HT(2A) receptor. In the midbrain, 5-HT synthetic enzyme, 5-HT transporter and 5-HT receptors mRNA levels were similar between groups. Our results emphasize a role for postsynaptic over presynaptic 5-HT receptors in mice which showed escalated aggression after the consumption of a moderate dose of alcohol. This gene expression profile of 5-HT neurotransmission components in the brain of mice may suggest a vulnerability trait for alcohol-heightened aggression.

  6. Chloramphenicol decreases CB1 receptor expression in the nucleus accumbens and prefrontal cortex and prevents amphetamine-induced conditioned place preference in rats.

    PubMed

    Amancio-Belmont, Octavio; Pérez-Vázquez, Diego; Ruiz-Contreras, Alejandra E; Pérez de la Mora, Miguel; Rueda-Orozco, Pavel E; Méndez-Díaz, Mónica; Prospero-Garcia, Oscar E

    2017-08-01

    Drug dependence seems to involve a learning and memory process. Since learning and memory depend on protein synthesis, drug dependence may depend on protein synthesis, too. Drug-induced reward is a crucial effect for the development of drug-dependence. We used chloramphenicol (CAP, a protein synthesis inhibitor), to evaluate its effects on amphetamine (amph)-seeking behavior, on CB1R expression and on protein synthesis in general, in specific areas of the brain. Two groups of Wistar adult male rats were subjected to amph-induced conditioned place preference (CPP). Rats in group 1 received amph and were kept in the chamber for 30min. Once this period elapsed, they received a subcutaneous injection of saline (veh) and were returned to their home-cage. Rats in group 2 were also treated with amph but received CAP (150mg/kgsc) instead of saline. Once CPP was evaluated rats were sacrificed and the prefrontal cortex (PFC), the nucleus accumbens (NAcc) and the hippocampus (Hipp) were isolated and prepared for CB1R Western blot analysis. A vivarium reared group of rats was added as a non-experimentally manipulated control group. Results indicate that group 1 developed CPP while increasing CB1R expression in the NAcc. Group 2 did not develop CPP, had lower CB1R expression in the PFC and lacked the CB1R increase in the NAcc observed in the amph+veh group. These results support the notion that among the underlying mechanisms for amph-seeking reward is an increase in CB1R, further supporting an interaction between dopamine/endocannabinoids in CPP learning. Copyright © 2017. Published by Elsevier Inc.

  7. Chronic Inactivation of the Orbitofrontal Cortex Increases Anxiety-Like Behavior and Impulsive Aggression, but Decreases Depression-Like Behavior in Rats

    PubMed Central

    Kuniishi, Hiroshi; Ichisaka, Satoshi; Matsuda, Sae; Futora, Eri; Harada, Riho; Hata, Yoshio

    2017-01-01

    The orbitofrontal cortex (OFC) is involved in emotional processing, and orbitofrontal abnormalities have often been observed in various affective disorders. Thus, chronic dysfunction of the OFC may cause symptoms of affective disorders, such as anxiety, depression and impulsivity. Previous studies have investigated the effect of orbitofrontal dysfunction on anxiety-like behavior and impulsive aggression in rodents, but the results are inconsistent possibly reflecting different methods of OFC inactivation. These studies used either a lesion of the OFC, which may affect other brain regions, or a transient inactivation of the OFC, whose effect may be restored in time and not reflect effects of chronic OFC dysfunction. In addition, there has been no study on the effect of orbitofrontal inactivation on depression-like behavior in rodents. Therefore, the present study examined whether chronic inactivation of the OFC by continuous infusion of a GABAA receptor agonist, muscimol, causes behavioral abnormalities in rats. Muscimol infusion inactivated the ventral and lateral part of the OFC. Following a week of OFC inactivation, the animals showed an increase in anxiety-like behavior in the open field test and light-dark test. Impulsive aggression was also augmented in the chronically OFC-inactivated animals because they showed increased frequency of fighting behavior induced by electric foot shock. On the other hand, chronic OFC inactivation reduced depression-like behavior as evaluated by the forced swim test. Additionally, it did not cause a significant change in corticosterone secretion in response to restraint stress. These data suggest that orbitofrontal neural activity is involved in the regulation of anxiety- and depression-like behaviors and impulsive aggression in rodents. PMID:28167902

  8. 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.

  9. Individual vulnerability to escalated aggressive behavior by a low dose of alcohol: decreased serotonin receptor mRNA in the prefrontal cortex of male mice

    PubMed Central

    Chiavegatto, S; Quadros, IMH; Ambar, G; Miczek, KA

    2009-01-01

    Low to moderate doses of alcohol consumption induce heightened aggressive behavior in some, but not all individuals. Individual vulnerability for this nonadaptive behavior may be determined by an interaction of genetic and environmental factors to the sensitivity of alcohol’s effects on brain and behavior. We used a previously established protocol for alcohol oral self-administration and characterized alcohol-heightened aggressive (AHA) mice as compared to alcohol-non-heightened (ANA) counterparts. A week later, we quantified mRNA steady state levels of several candidate genes in the serotonin (5-HT) system in different brain areas. We report a regionally selective and significant reduction of all 5-HT receptor subtype transcripts, except for 5HT3, in the prefrontal cortex of AHA mice. Comparable gene expression profile was previously observed in aggressive mice induced by social isolation or by an anabolic androgenic steroid. Additional change in the 5-HT1B receptor transcripts was seen in the amygdala and hypothalamus of AHA mice. In both these areas, 5-HT1B mRNA was elevated when compared to ANA mice. In the hypothalamus, AHA mice showed also increased transcripts for 5-HT2A receptor. In the midbrain, 5-HT synthetic enzyme, 5-HT transporter, and 5-HT receptors mRNA levels were similar between groups. Our results emphasize a role for postsynaptic over presynaptic 5-HT receptors in individuals who showed escalated aggression after the consumption of a moderate dose of alcohol. This gene expression profile of 5-HT neurotransmission components in the brain of mice may suggest a vulnerability trait for alcohol-heightened aggression. PMID:20002201

  10. Induction Therapy With Antithymocyte Globulin in Patients Undergoing Cardiac Transplantation Is Associated With Decreased Coronary Plaque Progression as Assessed by Intravascular Ultrasound.

    PubMed

    Azarbal, Babak; Cheng, Richard; Vanichsarn, Christopher; Patel, Jignesh K; Czer, Lawrence S; Chang, David H; Kittleson, Michelle M; Kobashigawa, Jon A

    2016-01-01

    Antithymocyte globulin (ATG) is used as induction therapy after cardiac transplant for enhancing immunosuppression and delaying the initiation of nephrotoxic drugs. It is unknown if ATG induction is associated with decreased coronary plaque progression by intravascular ultrasound (IVUS). Patients transplanted between March 2010 and December 2012 with baseline and 1-year IVUS were included. All patients transplanted were included in a secondary analysis. Change in plaque progression was measured in a blinded fashion on matched coronary segments and contrasted between patients induced with ATG and those who were not. One hundred and three patients were included in IVUS arms. Mean age at transplant was 55.8 ± 12.6 years, and 33.0% were female. Patients induced with ATG were more sensitized (54.3% versus 14.3%). Plaque progression was attenuated in patients who received ATG by changes in maximal intimal area (1.0 ± 1.2 versus 2.3 ± 2.6 mm(2); P = 0.001), maximal percent stenosis (6.3 ± 7.9 versus 12.8 ± 12.3%; = 0.003), maximal intimal thickness (0.2 ± 0.2 versus 0.3 ± 0.3 mm; P = 0.035), and plaque volume (0.5 ± 0.7 versus 1.0 ± 1.3 mm(3)/mm; P = 0.016). Rapid plaque progression by maximal percent stenosis (≥ 20%) occurred less frequently in the ATG arm (4.3% versus 26.3; P = 0.003). Survival (P = 0.242) and any treated rejection (P = 0.166) were not statistically different between groups. Patients receiving ATG had a higher rate of first-year infection (P = 0.003), perhaps related to increased intravenous antibiotic use immediately postoperatively, and a trend toward more biopsy-proven rejection (P = 0.073). Induction therapy with ATG is associated with reduced first-year coronary plaque progression as assessed by IVUS, despite an increased prevalence of sensitized patients with a trend toward more rejection. © 2016 American Heart Association, Inc.

  11. Effectiveness of a nursing intervention in decreasing the anxiety levels of family members of patients undergoing cardiac surgery: a randomized clinical trial.

    PubMed

    Hamester, Letícia; Souza, Emiliane Nogueira de; Cielo, Cibele; Moraes, Maria Antonieta; Pellanda, Lúcia Campos

    2016-08-15

    to verify the effectiveness of nursing orientation provided to families of patients in the immediate post-operative following cardiac surgery before the first visit to the post-anesthesia care unit, in decreasing anxiety levels, compared to the unit's routine orientation. open randomized clinical trial addressing family members in the waiting room before the first visit in the immediate post-operative period. The family members assigned to the intervention group received audiovisual orientation concerning the patients' conditions at the time and the control group received the unit's routine orientation. Outcome anxiety was assessed using the STAI-State. 210 individuals were included, 105 in each group, aged 46.4 years old on average (±14.5); 69% were female and 41% were the patients' children. The mean score obtained on the anxiety assessment in the intervention group was 41.3±8.6, while the control group scored 50.6±9.4 (p<0.001). a nursing intervention focused on providing guidance to families before their first visit to patients in the immediate post-operative period of cardiac surgery helps to decrease the levels of anxiety of companions, making them feel better prepared for the moment. ReBEC (Brazilian Clinical Trials Registry) and The Universal Trial Number (UTN), No. U1111-1145-6172. verificar a efetividade das orientações de enfermagem a familiares de pacientes em pós-operatório imediato de cirurgia cardíaca, antes da primeira visita na sala de recuperação pós-anestésica, nos níveis de ansiedade, comparados com a orientação de rotina da unidade. ensaio clínico randomizado, realizado com familiares abordados na sala de espera, antes da primeira visita no pós-operatório imediato. Familiares alocados no grupo intervenção receberam orientações audiovisuais sobre as condições em que o paciente se encontrava naquele momento, e o grupo controle recebeu as orientações de rotina da unidade. O desfecho ansiedade foi avaliado pelo invent

  12. Does infection by the hepatitis C virus decrease the response of immunization against the hepatitis B virus in individuals undergoing dialysis?

    PubMed

    Ferreira, Tarcila Maria Bonfim; Guimarães, Tácio Giordano Santana; Fontenele, Andrea Martins Melo; Salgado, Natalino; Ferreira, Adalgisa de Souza Paiva; Costa, Alessandra Porto de Macedo

    2017-04-27

    Vaccination is the most effective tool in preventing transmission of Hepatitis B Virus (HBV). The patient with chronic kidney disease (CKD) on dialysis appear to be at greater risk of becoming infected with this virus and does not show the same vaccine response when compared to patients without uremia. To evaluate the results related to the HBV vaccine and identify factors associated with the response in patients with CKD on hemodialysis. Individuals with HBsAG and negative anti-HBC, under hemodialysis were assessed in two units of São Luis, Maranhão and were undergone full vaccination schedule for HBV. They were divided in groups: anti-HBs10 mUI/mL and compared as to age, gender, presence of diabetes mellitus (DM), time on dialysis and anti-HCV status. Logistic regression analysis was performed to identify factors independently associated with the vaccine response. p10mUI/Ml (or = 5.239 IC: 1.279-21.459, p = 0.021). The rate of vaccine response to HBV in patients with CKD on dialysis was 70% and the lack of anti-HCV infection was associated with seroconversion of anti-HBs suggesting that infection by the hepatitis C virus may be a factor that decreases the response of the HBV vaccine in dialysis CKD patients. A vacinação é a medida mais efetiva na prevenção da transmissão do vírus da hepatite B (HBV). O portador de doença renal crônica (DRC) em diálise apresenta maior risco de se contaminar com este vírus e não tem a mesma resposta vacinal quando comparada com indivíduos sem uremia. Avaliar os resultados da vacina para o HBV e identificar fatores associados à resposta, em portadores de DRC em hemodiálise. Foram avaliados indivíduos com HBsAg e anti-HBc negativos, que estavam sob hemodiálise em duas unidades de São Luís, Maranhão e que haviam sido submetidos ao esquema completo de vacinação para o HBV. Foram distribuídos em dois grupos: anti-HBs < 10mUI/mL e anti-HBs ≥ 10mUI/mL e comparados quanto à idade, gênero, presença de diabetes

  13. Unilateral lesion of the nigrostriatal pathway decreases the response of fast-spiking interneurons in the medial prefrontal cortex to 5-HT1A receptor agonist and expression of the receptor in parvalbumin-positive neurons in the rat.

    PubMed

    Gui, Z H; Zhang, Q J; Liu, J; Zhang, L; Ali, U; Hou, C; Fan, L L; Sun, Y N; Wu, Z H; Hui, Y P

    2011-10-01

    5-Hydroxytryptamine(1A) (5-HT(1A)) receptors are expressed in the prefrontal cortical interneurons. Among these interneurons, calcium-binding protein parvalbumin (PV)-positive fast spiking (FS) interneurons play an important role in regulatory function of the prefrontal cortex. In the present study, the response of medial prefrontal cortex (mPFC) FS interneurons to the selective 5-HT(1A) receptor agonist 8-OH-DPAT and change in expression of 5-HT(1A) receptor on PV-positive neurons were examined in rats with 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (SNc) by using extracellular recording and double-labeling immunofluorescence histochemistry. Systemic administration of 8-OH-DPAT (1-243 μg/kg, i.v.) dose-dependently inhibited the mean firing rate of the FS interneurons in sham-operated and the lesioned rats, respectively. The cumulative doses producing inhibition in the lesioned rats (243 μg/kg) was significantly higher than that of sham-operated rats (27 μg/kg). Furthermore, the local application of 8-OH-DPAT (0.01 μg) in the mPFC inhibited the FS interneurons in sham-operated rats, while having no effect on firing rate of the FS interneurons in the lesioned rats. In contrast to sham-operated rats, the lesion of the SNc in rats did not cause the change of PV-positive neurons in the prelimbic prefrontal cortex, a subregion of the mPFC, whereas the lesion of the SNc markedly reduced in percentage of PV-positive neurons expressing 5-HT(1A) receptors. Our results indicate that degeneration of the nigrostriatal pathway results in the decreased response of FS interneurons in the mPFC to 5-HT(1A) receptor stimulation, which attributes to down-regulation of 5-HT(1A) receptor expression in these interneurons.

  14. Cerebral Oedema, Blood-Brain Barrier Breakdown and the Decrease in Na(+),K(+)-ATPase Activity in the Cerebral Cortex and Hippocampus are Prevented by Dexamethasone in an Animal Model of Maple Syrup Urine Disease.

    PubMed

    Rosa, Luciana; Galant, Leticia S; Dall'Igna, Dhébora M; Kolling, Janaina; Siebert, Cassiana; Schuck, Patrícia F; Ferreira, Gustavo C; Wyse, Angela T S; Dal-Pizzol, Felipe; Scaini, Giselli; Streck, Emilio L

    2016-08-01

    Maple syrup urine disease (MSUD) is a rare metabolic disorder associated with acute and chronic brain dysfunction. This condition has been shown to lead to macroscopic cerebral alterations that are visible on imaging studies. Cerebral oedema is widely considered to be detrimental for MSUD patients; however, the mechanisms involved are still poorly understood. Therefore, we investigated whether acute administration of branched-chain amino acids (BCAA) causes cerebral oedema, modifies the Na(+),K(+)-ATPase activity, affects the permeability of the blood-brain barrier (BBB) and alters the levels of cytokines in the hippocampus and cerebral cortex of 10-day-old rats. Additionally, we investigated the influence of concomitant administration of dexamethasone on the alterations caused by BCAA. Our results showed that the animals submitted to the model of MSUD exhibited an increase in the brain water content, both in the cerebral cortex and in the hippocampus. By investigating the mechanism of cerebral oedema, we discovered an association between H-BCAA and the Na(+),K(+)-ATPase activity and the permeability of the BBB to small molecules. Moreover, the H-BCAA administration increases Il-1β, IL-6 and TNF-α levels in the hippocampus and cerebral cortex, whereas IL-10 levels were decreased in the hippocampus. Interestingly, we showed that the administration of dexamethasone successfully reduced cerebral oedema, preventing the inhibition of Na(+),K(+)-ATPase activity, BBB breakdown and the increase in the cytokines levels. In conclusion, these findings suggest that dexamethasone can improve the acute cerebral oedema and brain injury associated with high levels of BCAA, either through a direct effect on brain capillary Na(+),K(+)-ATPase or through a generalized effect on the permeability of the BBB to all compounds.

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

    PubMed

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

    2015-10-15

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

  16. Decreased anxiety-like behavior and locomotor/exploratory activity, and modulation in hypothalamus, hippocampus, and frontal cortex redox profile in sexually receptive female rats after short-term exposure to male chemical cues.

    PubMed

    Behr, Guilherme Antônio; da Motta, Leonardo Lisbôa; de Oliveira, Marcos Roberto; Oliveira, Max William Soares; Hoff, Mariana Leivas Müller; Silvestrin, Roberta Bristot; Moreira, José Cláudio Fonseca

    2009-05-16

    Chemical cues are widely used for intraspecific social communication in a vast majority of living organisms ranging from bacteria to mammals. As an example, mammals release olfactory cues with urine that promote neuroendocrine modulations with changes in behavior and physiology in the receiver. In this work, four-month-old Wistar (regular 4-day cyclic) virgin female rats were utilized in the proestrus-to-estrus phase of the reproductive cycle for experimental exposure. In an isolated room, female rats were exposed for 90 min to male-soiled bedding (MSB). Elevated plus-maze assay, open field test, and light/dark box task were performed to analyze behavioral alterations on females after exposure. For biochemical assays, female rats were killed and the hypothalamus, hippocampus, and frontal cortex were isolated for further analysis. Antioxidant enzyme activities (superoxide dismutase, catalase and glutathione peroxidase), non-enzymatic antioxidant defense measurements (TRAP and TAR), and the oxidative damage parameters (TBARS, Carbonyl and SH content) were analyzed. In behavioral analyses we observe that female rats show decreased anxiety and locomotory/exploratory activities after MSB exposure. In biochemical assays we observed an increase in both enzymatic and non-enzymatic antioxidant defenses in different central nervous system (CNS) structures analyzed 30 and 90 min after MSB exposure. Furthermore, hippocampus and frontal cortex showed diminished free radical oxidative damage at 180 and 240 min after exposure. These results provide the first evidence that oxidative profile of female CNS structures are altered by chemical cues present in the MSB, thus suggesting that pheromonal communication is able to modulate radical oxygen species production and/or clearance in the female brain.

  17. Effectiveness of positive end-expiratory pressure, decreased fraction of inspired oxygen and vital capacity recruitment maneuver in the prevention of pulmonary atelectasis in patients undergoing general anesthesia: a systematic review.

    PubMed

    Martin, Jennifer Bourgeois; Garbee, Deborah; Bonanno, Laura

    2015-09-16

    General anesthesia causes impairment of gas exchange in the lungs that results in decreased oxygenation of the blood; atelectasis is the principle cause of this impaired gas exchange. Anesthesia delivery varies between providers and there is no standard practice to decrease the incidence of postoperative atelectasis. To assess the effectiveness of three identified interventions, either individually or combined, in the development of postoperative pulmonary atelectasis in patients undergoing general anesthesia. The review considered participants over 18 years for inclusion. The American Society of Anesthesiologists classification of subjects was I, II or III. Participants underwent a variety of surgical procedures during which general anesthesia was administered. TYPES OF INTERVENTION(S)/PHENOMENA OF INTEREST: The review focused on the following interventions: positive end-expiratory pressure, decreased fraction of inspired oxygen content, and/or a vital capacity recruitment maneuver during general anesthesia in comparison to general anesthesia performed without the use of these interventions. TYPES OF STUDIES: Randomized controlled trials that evaluated the effectiveness of any of the proposed interventions, individually or in combination, in the prevention of postoperative atelectasis during general anesthesia were considered for inclusion. TYPES OF OUTCOMES: This review considered studies that reported the incidence of postoperative atelectasis. Atelectasis was measured by lung density measurements, in Hounsfield units, with computed tomography scans, decreased PaO2 levels (partial pressure of oxygen dissolved in arterial blood), and pulmonary function tests. A three-step search strategy was utilized in this review. Studies published in English, without date limits, were considered for inclusion. Databases searched were: CINAHL, MEDLINE, ISI Web of Science, EMBASE, ProQuest Theses and Dissertations and ClinicalTrials.gov, (specifically the National Heart, Lung

  18. Preoperative levosimendan decreases mortality and the development of low cardiac output in high-risk patients with severe left ventricular dysfunction undergoing coronary artery bypass grafting with cardiopulmonary bypass

    PubMed Central

    Levin, Ricardo; Degrange, Marcela; Del Mazo, Carlos; Tanus, Eduardo; Porcile, Rafael

    2012-01-01

    BACKGROUND: The calcium sensitizer levosimendan has been used in cardiac surgery for the treatment of postoperative low cardiac output syndrome (LCOS) and difficult weaning from cardiopulmonary bypass (CPB). OBJECTIVES: To evaluate the effects of preoperative treatment with levosimendan on 30-day mortality, the risk of developing LCOS and the requirement for inotropes, vasopressors and intra-aortic balloon pumps in patients with severe left ventricular dysfunction. METHODS: Patient with severe left ventricular dysfunction and an ejection fraction <25% undergoing coronary artery bypass grafting with CPB were admitted 24 h before surgery and were randomly assigned to receive levosimendan (loading dose 10 μg/kg followed by a 23 h continuous infusion of 0.1μg/kg/min) or a placebo. RESULTS: From December 1, 2002 to June 1, 2008, a total of 252 patients were enrolled (127 in the levosimendan group and 125 in the control group). Individuals treated with levosimendan exhibited a lower incidence of complicated weaning from CPB (2.4% versus 9.6%; P<0.05), decreased mortality (3.9% versus 12.8%; P<0.05) and a lower incidence of LCOS (7.1% versus 20.8%; P<0.05) compared with the control group. The levosimendan group also had a lower requirement for inotropes (7.9% versus 58.4%; P<0.05), vasopressors (14.2% versus 45.6%; P<0.05) and intra-aortic balloon pumps (6.3% versus 30.4%; P<0.05). CONCLUSION: Patients with severe left ventricle dysfunction (ejection fraction <25%) undergoing coronary artery bypass grafting with CPB who were pretreated with levosimendan exhibited lower mortality, a decreased risk for developing LCOS and a reduced requirement for inotropes, vasopressors and intra-aortic balloon pumps. Studies with a larger number of patients are required to confirm whether these findings represent a new strategy to reduce the operative risk in this high-risk patient population. PMID:23620700

  19. Evaluation of sexual function outcomes in women undergoing vaginal rejuvenation/vaginoplasty procedures for symptoms of vaginal laxity/decreased vaginal sensation utilizing validated sexual function questionnaire (PISQ-12).

    PubMed

    Moore, Robert D; Miklos, John R; Chinthakanan, Orawee

    2014-03-01

    Sexual function outcomes were analyzed in a group of women (n = 78) presenting for vaginal rejuvenation/vaginoplasty procedure for a chief complaint of vaginal laxity and decreased sensation with intercourse. Outcomes were analyzed utilizing the validated Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12 (PISQ-12) before and at least 6 months after repair with vaginal rejuvenation/vaginoplasty procedure (VR). Mean age was 43.6 ± 7.9 (range 25-62), and 19 patients (24.3%) were found to have prolapse at time of initial exam and underwent vaginal vault suspension in addition to VR. Compared preoperatively and postoperatively, the overall sexual function (Total PISQ-12) statistically improved (30.3 ± 6.6 vs. 38.2 ± 5.2, P < 0.001). All individual scores statistically improved except in 3 categories in which there was no change (Q1-desire, Q5-pain, and Q11- partner premature ejaculation). Overall sexual satisfaction improved as well as subcategories of increased sexual excitement during intercourse and overall increase in intensity of orgasms. Pain with intercourse subscores were found to be no different from preoperatively to postoperatively. Previous studies have shown that sexual function improves with repair of prolapse; however, this is the first study to show improved function using a validated questionnaire in patients undergoing VR for laxity.

  20. Decreased CD95 expression on naive T cells from HIV-infected persons undergoing highly active anti-retroviral therapy (HAART) and the influence of IL-2 low dose administration

    PubMed Central

    Amendola, A; Poccia, F; Martini, F; Gioia, C; Galati, V; Pierdominici, M; Marziali, M; Pandolfi, F; Colizzi, V; Piacentini, M; Girardi, E; D'Offizi, G

    2000-01-01

    The functional recovery of the immune system in HIV-infected persons receiving HAART and the role of adjuvant immune therapy are still matters of intensive investigation. We analysed the effects of HAART combined with cytokines in 22 naive asymptomatic individuals, randomized to receive HAART (n = 6), HAART plus a low dose (1000 000 U/daily) of rIL-2 (n = 8), and HAART plus rIL-2 after previous administration of granulocyte colony-stimulating factor (n = 8). After 3 months of therapy, increased CD4+ T cell counts and diminished viral loads were observed in all patients, independently of cytokine addition. A decreased expression of CD95 (Apo 1/Fas) was evident in all groups when compared with values before therapy. The percentages of peripheral blood mononuclear cells (PBMC) expressing CD95 after therapy decreased by 15%, 22% and 18% in the three treatment groups, respectively (P < 0·05). Analysis of PBMC subsets demonstrated that CD95 expression was significantly reduced on CD45RA+CD62L+ naive T cells (25·3%, 22·4%, and 18·6%, respectively; P < 0·05) in each group, after therapy. Accordingly, all patients showed a reduced rate of in vitro spontaneous apoptosis (P < 0·05). Another effect induced by HAART was a significant increase in IL-2Rα expression on total PBMC (P < 0·05), independently of cytokine addition. Altogether, our results suggest that very low dose administration of rIL-2 (1000 000 U/daily) may be not enough to induce a significant improvement in the immune system as regards HAART alone. The employment of higher doses of recombinant cytokines and/or different administration protocols in clinical trials might however contribute to ameliorate the immune reconstitution in patients undergoing HAART. PMID:10792383

  1. Decreased expression of Freud-1/CC2D1A, a transcriptional repressor of the 5-HT1A receptor, in the prefrontal cortex of subjects with major depression.

    PubMed

    Szewczyk, Bernadeta; Albert, Paul R; Rogaeva, Anastasia; Fitzgibbon, Heidi; May, Warren L; Rajkowska, Grazyna; Miguel-Hidalgo, Jose J; Stockmeier, Craig A; Woolverton, William L; Kyle, Patrick B; Wang, Zhixia; Austin, Mark C

    2010-09-01

    Serotonin1A (5-HT(1A)) receptors are reported altered in the brain of subjects with major depressive disorder (MDD). Recent studies have identified transcriptional regulators of the 5-HT(1A) receptor and have documented gender-specific alterations in 5-HT(1A) transcription factor and 5-HT(1A) receptors in female MDD subjects. The 5' repressor element under dual repression binding protein-1 (Freud-1) is a calcium-regulated repressor that negatively regulates the 5-HT(1A) receptor gene. This study documented the cellular expression of Freud-1 in the human prefrontal cortex (PFC) and quantified Freud-1 protein in the PFC of MDD and control subjects as well as in the PFC of rhesus monkeys chronically treated with fluoxetine. Freud-1 immunoreactivity was present in neurons and glia and was co-localized with 5-HT(1A) receptors. Freud-1 protein level was significantly decreased in the PFC of male MDD subjects (37%, p=0.02) relative to gender-matched control subjects. Freud-1 protein was also reduced in the PFC of female MDD subjects (36%, p=0.18) but was not statistically significant. When the data was combined across genders and analysed by age, the decrease in Freud-1 protein level was greater in the younger MDD subjects (48%, p=0.01) relative to age-matched controls as opposed to older depressed subjects. Similarly, 5-HT(1A) receptor protein was significantly reduced in the PFC of the younger MDD subjects (48%, p=0.01) relative to age-matched controls. Adult male rhesus monkeys administered fluoxetine daily for 39 wk revealed no significant change in cortical Freud-1 or 5-HT(1A) receptor proteins compared to vehicle-treated control monkeys. Reduced protein expression of Freud-1 in MDD subjects may reflect dysregulation of this transcription factor, which may contribute to the altered regulation of 5-HT(1A) receptors observed in subjects with MDD. These data may also suggest that reductions in Freud-1 protein expression in the PFC may be associated with early onset of

  2. Decreased expression of Freud-1/CC2D1A, a transcriptional repressor of the 5-HT1A receptor, in the prefrontal cortex of subjects with major depression

    PubMed Central

    Szewczyk, Bernadeta; Albert, Paul R.; Rogaeva, Anastasia; Fitzgibbon, Heidi; May, Warren L.; Rajkowska, Grazyna; Miguel-Hidalgo, Jose J.; Stockmeier, Craig A.; Woolverton, William L.; Kyle, Patrick B.; Wang, Zhixia; Austin, Mark C.

    2011-01-01

    Serotonin1A (5-HT1A) receptors are reported altered in the brain of subjects with major depressive disorder (MDD). Recent studies have identified transcriptional regulators of the 5-HT1A receptor and have documented gender-specific alterations in 5-HT1A transcription factor and 5-HT1A receptors in female MDD subjects. The 5′ repressor element under dual repression binding protein-1 (Freud-1) is a calcium-regulated repressor that negatively regulates the 5-HT1A receptor gene. This study documented the cellular expression of Freud-1 in the human prefrontal cortex (PFC) and quantified Freud-1 protein in the PFC of MDD and control subjects as well as in the PFC of rhesus monkeys chronically treated with fluoxetine. Freud-1 immunoreactivity was present in neurons and glia and was co-localized with 5-HT1A receptors. Freud-1 protein level was significantly decreased in the PFC of male MDD subjects (37%, p=0.02) relative to gender-matched control subjects. Freud-1 protein was also reduced in the PFC of female MDD subjects (36%, p=0.18) but was not statistically significant. When the data was combined across genders and analysed by age, the decrease in Freud-1 protein level was greater in the younger MDD subjects (48%, p=0.01) relative to age-matched controls as opposed to older depressed subjects. Similarly, 5-HT1A receptor protein was significantly reduced in the PFC of the younger MDD subjects (48%, p=0.01) relative to age-matched controls. Adult male rhesus monkeys administered fluoxetine daily for 39 wk revealed no significant change in cortical Freud-1 or 5-HT1A receptor proteins compared to vehicle-treated control monkeys. Reduced protein expression of Freud-1 in MDD subjects may reflect dysregulation of this transcription factor, which may contribute to the altered regulation of 5-HT1A receptors observed in subjects with MDD. These data may also suggest that reductions in Freud-1 protein expression in the PFC may be associated with early onset of MDD. PMID

  3. Genetic influences on thinning of the cerebral cortex during development.

    PubMed

    van Soelen, I L C; Brouwer, R M; van Baal, G C M; Schnack, H G; Peper, J S; Collins, D L; Evans, A C; Kahn, R S; Boomsma, D I; Hulshoff Pol, H E

    2012-02-15

    During development from childhood to adulthood the human brain undergoes considerable thinning of the cerebral cortex. Whether developmental cortical thinning is influenced by genes and if independent genetic factors influence different parts of the cortex is not known. Magnetic resonance brain imaging was done in twins at age 9 (N = 190) and again at age 12 (N = 125; 113 repeated measures) to assess genetic influences on changes in cortical thinning. We find considerable thinning of the cortex between over this three year interval (on average 0.05 mm; 1.5%), particularly in the frontal poles, and orbitofrontal, paracentral, and occipital cortices. Cortical thinning was highly heritable at age 9 and age 12, and the degree of genetic influence differed for the various areas of the brain. One genetic factor affected left inferior frontal (Broca's area), and left parietal (Wernicke's area) thinning; a second factor influenced left anterior paracentral (sensory-motor) thinning. Two factors influenced cortical thinning in the frontal poles: one of decreasing influence over time, and another independent genetic factor emerging at age 12 in left and right frontal poles. Thus, thinning of the cerebral cortex is heritable in children between the ages 9 and 12. Furthermore, different genetic factors are responsible for variation in cortical thickness at ages 9 and 12, with independent genetic factors acting on cortical thickness across time and between various brain areas during childhood brain development.

  4. Growth and refinement of excitatory synapses in the human auditory cortex.

    PubMed

    Pundir, Arvind Singh; Singh, Utkarsha A; Ahuja, Nikhil; Makhija, Sonal; Dikshit, P C; Radotra, Bishan; Kumar, Praveen; Shankar, S K; Mahadevan, Anita; Roy, T S; Iyengar, Soumya

    2016-09-01

    We had earlier demonstrated a neurofilament-rich plexus of axons in the presumptive human auditory cortex during fetal development which became adult-like during infancy. To elucidate the origin of these axons, we studied the expression of the vesicular glutamate transporters (VGLUT) 1 and 2 in the human auditory cortex at different stages of development. While VGLUT-1 expression predominates in intrinsic and cortico-cortical synapses, VGLUT-2 expression predominates in thalamocortical synapses. Levels of VGLUT-2 mRNA were higher in the auditory cortex before birth compared to postnatal development. In contrast, levels of VGLUT-1 mRNA were low before birth and increased during postnatal development to peak during childhood and then began to decrease in adolescence. Both VGLUT-1 and VGLUT-2 proteins were present in the human auditory cortex as early as 15GW. Further, immunohistochemistry revealed that the supra- and infragranular layers were more immunoreactive for VGLUT-1 compared to that in Layer IV at 34GW and this pattern was maintained until adulthood. As for VGLUT-1 mRNA, VGLUT-1 synapses increased in density between prenatal development and childhood in the human auditory cortex after which they appeared to undergo attrition or pruning. The adult pattern of VGLUT-2 immunoreactivity (a dense band of VGLUT-2-positive terminals in Layer IV) also began to appear in the presumptive Heschl's gyrus at 34GW. The density of VGLUT-2-positive puncta in Layer IV increased between prenatal development and adolescence, followed by a decrease in adulthood, suggesting that thalamic axons which innervate the human auditory cortex undergo pruning comparatively late in development.

  5. Learning in the Rodent Motor Cortex.

    PubMed

    Peters, Andrew J; Liu, Haixin; Komiyama, Takaki

    2017-03-31

    The motor cortex is far from a stable conduit for motor commands and instead undergoes significant changes during learning. An understanding of motor cortex plasticity has been advanced greatly using rodents as experimental animals. Two major focuses of this research have been on the connectivity and activity of the motor cortex. The motor cortex exhibits structural changes in response to learning, and substantial evidence has implicated the local formation and maintenance of new synapses as crucial substrates of motor learning. This synaptic reorganization translates into changes in spiking activity, which appear to result in a modification and refinement of the relationship between motor cortical activity and movement. This review presents the progress that has been made using rodents to establish the motor cortex as an adaptive structure that supports motor learning. Expected final online publication date for the Annual Review of Neuroscience Volume 40 is July 8, 2017. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  6. Vibrissa motor cortex activity suppresses contralateral whisking behavior.

    PubMed

    Ebbesen, Christian Laut; Doron, Guy; Lenschow, Constanze; Brecht, Michael

    2017-01-01

    Anatomical, stimulation and lesion data implicate vibrissa motor cortex in whisker motor control. Work on motor cortex has focused on movement generation, but correlations between vibrissa motor cortex activity and whisking are weak. The exact role of vibrissa motor cortex remains unknown. We recorded vibrissa motor cortex neurons during various forms of vibrissal touch, which were invariably associated with whisker protraction and movement. Free whisking, object palpation and social touch all resulted in decreased cortical activity. To understand this activity decrease, we performed juxtacellular recordings, nanostimulation and in vivo whole-cell recordings. Social touch resulted in decreased spiking activity, decreased cell excitability and membrane hyperpolarization. Activation of vibrissa motor cortex by intracortical microstimulation elicited whisker retraction, as if to abort vibrissal touch. Various vibrissa motor cortex inactivation protocols resulted in contralateral protraction and increased whisker movements. These data collectively point to movement suppression as a prime function of vibrissa motor cortex activity.

  7. High-Dose Statin Pretreatment Decreases Periprocedural Myocardial Infarction and Cardiovascular Events in Patients Undergoing Elective Percutaneous Coronary Intervention: A Meta-Analysis of Twenty-Four Randomized Controlled Trials

    PubMed Central

    Wang, Le; Peng, Pingan; Zhang, Ou; Xu, Xiaohan; Yang, Shiwei; Zhao, Yingxin; Zhou, Yujie

    2014-01-01

    Background Evidence suggests that high-dose statin pretreatment may reduce the risk of periprocedural myocardial infarction (PMI) and major adverse cardiac events (MACE) for certain patients; however, previous analyses have not considered patients with a history of statin maintenance treatment. In this meta-analysis of randomized controlled trials (RCTs), we reevaluated the efficacy of short-term high-dose statin pretreatment to prevent PMI and MACE in an expanded set of patients undergoing elective percutaneous coronary intervention. Methods We searched the PubMed/Medline database for RCTs that compared high-dose statin pretreatment with no statin or low-dose statin pretreatment as a prevention of PMI and MACE. We evaluated the incidence of PMI and MACE, including death, spontaneous myocardial infarction, and target vessel revascularization at the longest follow-up for each study for subgroups stratified by disease classification and prior low-dose statin treatment. Results Twenty-four RCTs with a total of 5,526 patients were identified. High-dose statin pretreatment was associated with 59% relative reduction in PMI (odds ratio [OR]: 0.41; 95% confidence interval [CI]: 0.34–0.49; P<0.00001) and 39% relative reduction in MACE (OR: 0.61; 95% CI: 0.45–0.83; P = 0.002). The benefit of high-dose statin pretreatment on MACE was significant for statin-naive patients (OR: 0.69; 95% CI: 0.50–0.95; P = 0.02) and prior low dose statin-treated patients (OR: 0.28; 95% CI: 0.12–0.65; P = 0.003); and for patients with acute coronary syndrome (OR: 0.52; 95% CI: 0.34–0.79; P = 0.003), but not for patients with stable angina (OR: 0.71; 95% CI 0.45–1.10; P = 0.12). Long-term effects on survival were less obvious. Conclusions High-dose statin pretreatment can result in a significant reduction in PMI and MACE for patients undergoing elective PCI. The positive effect of high-dose statin pretreatment on PMI and MACE is significant for statin

  8. Decrease in NMDA receptor-signalling activity in the anterior cingulate cortex diminishes defensive behaviour and unconditioned fear-induced antinociception elicited by GABAergic tonic inhibition impairment in the posterior hypothalamus.

    PubMed

    Falconi-Sobrinho, Luiz Luciano; Anjos-Garcia, Tayllon Dos; de Oliveira, Ricardo; Coimbra, Norberto Cysne

    2017-09-19

    Acute γ-aminobutyric acid (GABA) disinhibition in the posterior hypothalamus (PH) elicits defensive reactions that are considered anxiety- and panic attack-like behaviour, and these defensive reactions are followed by antinociception. Evidence indicates that the PH connects with the medial prefrontal cortex, particularly the anterior cingulate cortex (ACC), which seems to regulate these unconditioned fear-induced defensive responses. However, few studies have shown the participation of cortical regions in the control of behavioural and antinociceptive responses organised by diencephalic structures. It has been suggested that the glutamatergic system can mediate this cortical influence, as excitatory imbalance is believed to play a role in both defensive mechanisms. Thus, the aim of the present study was to investigate the involvement of ACC glutamatergic connections via blockade of local N-methyl-D-aspartate (NMDA) receptors to elaborate panic-like defensive behaviours and unconditioned fear-induced antinociception organised by PH neurons. Wistar rats were treated with microinjections of 0.9% NaCl or LY235959 (a selective NMDA receptor antagonist) in the ACC at different concentrations (2, 4 and 8 nmol/0.2μL), followed by GABAA receptor blockade in the PH. Defensive reactions were analysed for 20min, and the nociceptive threshold was then measured at 10-min intervals for 60min. Pretreatment of the ACC with LY235959 reduced both panic-like defensive behaviour and fear-induced antinociception evoked by PH GABAergic disinhibition. Our findings suggest that ACC NMDA receptor-signalled glutamatergic inputs play a relevant role in the organisation of anxiety- and panic attack-like behaviours and in fear-induced antinociception. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

  9. Super pharmacological levels of calcitriol (1,25-(OH)2D3) inhibits mineral deposition and decreases cell proliferation in a strain dependent manner in chicken mesenchymal stem cells undergoing osteogenic differentiation in vitro.

    PubMed

    Pande, Vivek V; Chousalkar, Kapil C; Bhanugopan, Marie S; Quinn, Jane C

    2015-11-01

    The biologically active form of vitamin D₃, calcitriol (1,25-(OH)₂D₃), plays a key role in mineral homeostasis and bone formation and dietary vitamin D₃deficiency is a major cause of bone disorders in poultry. Supplementary dietary cholecalciferol (25-hydroxyvitamin D, 25-OH), the precursor of calcitriol, is commonly employed to combat this problem; however, dosage must be carefully determined as excess dietary vitamin D can cause toxicity resulting in a decrease in bone calcification, hypercalcinemia and renal failure. Despite much research on the therapeutic administration of dietary vitamin D in humans, the relative sensitivity of avian species to exogenous vitamin D has not been well defined. In order to determine the effects of exogenous 1,25-(OH)₂D₃during avian osteogenesis, chicken bone marrow-derived mesenchymal stem cells (BM-MSCs) were exposed to varying doses of 1,25-(OH)₂D₃during in vitro osteogenic differentiation and examined for markers of early proliferation and osteogenic induction. Similar to humans and other mammals, poultry BM-MSCs were found to be highly sensitive to exogenous 1,25-(OH)₂D₃with super pharmacological levels exerting significant inhibition of mineralization and loss of cell proliferation in vitro. Strain related differences were apparent, with BM-MCSs derived from layers strains showing a higher level of sensitivity to 1,25-(OH)₂D₃than those from broilers. These data suggest that understanding species and strain specific sensitivities to 1,25-(OH)₂D₃is important for optimizing bone health in the poultry industry and that use of avian BM-MSCs are a useful tool for examining underlying effects of genetic variation in poultry.

  10. Development and function of human cerebral cortex neural networks from pluripotent stem cells in vitro

    PubMed Central

    Kirwan, Peter; Turner-Bridger, Benita; Peter, Manuel; Momoh, Ayiba; Arambepola, Devika; Robinson, Hugh P. C.; Livesey, Frederick J.

    2015-01-01

    A key aspect of nervous system development, including that of the cerebral cortex, is the formation of higher-order neural networks. Developing neural networks undergo several phases with distinct activity patterns in vivo, which are thought to prune and fine-tune network connectivity. We report here that human pluripotent stem cell (hPSC)-derived cerebral cortex neurons form large-scale networks that reflect those found in the developing cerebral cortex in vivo. Synchronised oscillatory networks develop in a highly stereotyped pattern over several weeks in culture. An initial phase of increasing frequency of oscillations is followed by a phase of decreasing frequency, before giving rise to non-synchronous, ordered activity patterns. hPSC-derived cortical neural networks are excitatory, driven by activation of AMPA- and NMDA-type glutamate receptors, and can undergo NMDA-receptor-mediated plasticity. Investigating single neuron connectivity within PSC-derived cultures, using rabies-based trans-synaptic tracing, we found two broad classes of neuronal connectivity: most neurons have small numbers (<10) of presynaptic inputs, whereas a small set of hub-like neurons have large numbers of synaptic connections (>40). These data demonstrate that the formation of hPSC-derived cortical networks mimics in vivo cortical network development and function, demonstrating the utility of in vitro systems for mechanistic studies of human forebrain neural network biology. PMID:26395144

  11. Development and function of human cerebral cortex neural networks from pluripotent stem cells in vitro.

    PubMed

    Kirwan, Peter; Turner-Bridger, Benita; Peter, Manuel; Momoh, Ayiba; Arambepola, Devika; Robinson, Hugh P C; Livesey, Frederick J

    2015-09-15

    A key aspect of nervous system development, including that of the cerebral cortex, is the formation of higher-order neural networks. Developing neural networks undergo several phases with distinct activity patterns in vivo, which are thought to prune and fine-tune network connectivity. We report here that human pluripotent stem cell (hPSC)-derived cerebral cortex neurons form large-scale networks that reflect those found in the developing cerebral cortex in vivo. Synchronised oscillatory networks develop in a highly stereotyped pattern over several weeks in culture. An initial phase of increasing frequency of oscillations is followed by a phase of decreasing frequency, before giving rise to non-synchronous, ordered activity patterns. hPSC-derived cortical neural networks are excitatory, driven by activation of AMPA- and NMDA-type glutamate receptors, and can undergo NMDA-receptor-mediated plasticity. Investigating single neuron connectivity within PSC-derived cultures, using rabies-based trans-synaptic tracing, we found two broad classes of neuronal connectivity: most neurons have small numbers (<10) of presynaptic inputs, whereas a small set of hub-like neurons have large numbers of synaptic connections (>40). These data demonstrate that the formation of hPSC-derived cortical networks mimics in vivo cortical network development and function, demonstrating the utility of in vitro systems for mechanistic studies of human forebrain neural network biology.

  12. Decreased face primary motor cortex (face-M1) excitability induced by noxious stimulation of the rat molar tooth pulp is dependent on the functional integrity of medullary astrocytes.

    PubMed

    Pun, H; Awamleh, L; Lee, J-C; Avivi-Arber, L

    2016-03-01

    We have recently shown that application of the small-fiber excitant and inflammatory irritant mustard oil (MO) to the rat molar tooth pulp can decrease face-M1 excitability, but increase the excitability of trigeminal medullary dorsal horn (MDH) nociceptive neurons and that application of the astrocytic inhibitor methionine sulfoximine (MSO) to the face-M1 or MDH can attenuate the MO-induced changes. The present study aimed to determine whether medullary MSO application could modulate the MO-induced decreased face-M1 excitability. Under ketamine general anesthesia, electromyographic (EMG) electrodes were implanted into the right anterior digastric (RAD, jaw-opening muscle) of adult male Sprague-Dawley rats. A microelectrode was positioned at a low-threshold (≤30 μA) site in the left face-M1. Then MO (n = 16) or control-solution (n = 16) was applied to the previously exposed molar tooth pulp, and intracortical microstimulation threshold intensities for evoking RAD EMG activities were monitored for 15 min. MSO (0.1 mM, n = 8) or phosphate-buffered saline (PBS, n = 8) was then applied to the MDH and RAD thresholds monitored every 15 min for 120 min. Statistics used ANOVA followed by post hoc Bonferroni as appropriate (p < 0.05). As compared to baseline, RAD thresholds significantly increased (i.e., decreased excitability) within 1 min (26.3 ± 7.9%, p = 0.007) and peaked at 15 min following pulpal MO application (49.9 ± 5.7%, p < 0.001) but not following control-solution. Following MSO (but not PBS) application to the medulla, RAD thresholds significantly decreased within 15 min (26.5 ± 3.0%, p = 0.05) and at 60 min approached 6.3 ± 2.4%, of baseline values (p = 0.1). These novel findings suggest that clinically related motor disturbances arising from dental pain may involve decreased face-M1 excitability that is modulated by medullary astrocytes.

  13. Actin cortex architecture regulates cell surface tension.

    PubMed

    Chugh, Priyamvada; Clark, Andrew G; Smith, Matthew B; Cassani, Davide A D; Dierkes, Kai; Ragab, Anan; Roux, Philippe P; Charras, Guillaume; Salbreux, Guillaume; Paluch, Ewa K

    2017-06-01

    Animal cell shape is largely determined by the cortex, a thin actin network underlying the plasma membrane in which myosin-driven stresses generate contractile tension. Tension gradients result in local contractions and drive cell deformations. Previous cortical tension regulation studies have focused on myosin motors. Here, we show that cortical actin network architecture is equally important. First, we observe that actin cortex thickness and tension are inversely correlated during cell-cycle progression. We then show that the actin filament length regulators CFL1, CAPZB and DIAPH1 regulate mitotic cortex thickness and find that both increasing and decreasing thickness decreases tension in mitosis. This suggests that the mitotic cortex is poised close to a tension maximum. Finally, using a computational model, we identify a physical mechanism by which maximum tension is achieved at intermediate actin filament lengths. Our results indicate that actin network architecture, alongside myosin activity, is key to cell surface tension regulation.

  14. Decreased face primary motor cortex (face-M1) excitability induced by noxious stimulation of the rat molar tooth pulp is dependent on the functional integrity of face-M1 astrocytes.

    PubMed

    Awamleh, L; Pun, H; Lee, J-C; Avivi-Arber, L

    2015-04-01

    Acute inflammatory dental pain is a prevalent condition often associated with limited jaw movements. Mustard oil (MO, a small-fiber excitant/inflammatory irritant) application to the rat molar tooth pulp induces increased excitability (i.e., central sensitization) of trigeminal medullary dorsal horn (MDH) nociceptive neurons that can be modulated by MDH application of the astrocytic inhibitor methionine sulfoximine (MSO). The objectives of the study were to determine whether MO application to the rat right maxillary first molar tooth pulp affects left face-M1 excitability manifested as altered intracortical microstimulation thresholds for evoking electromyographic activity in the right anterior digastric (RAD, jaw-opening muscle), and whether MSO application to face-M1 can modulate this MO effect. Under Ketamine general anesthesia, Sprague-Dawley male rats had a microelectrode positioned at a low-threshold (≤30 μA) face-M1 site. Then MO (n = 16) or control solution (n = 16) was applied to the previously exposed tooth pulp, and RAD threshold was monitored for 15 min. MSO (0.1 mM, n = 8) or saline (n = 8) was then applied to the face-M1, and RAD thresholds were monitored every 15 min for 120 min. ANOVA followed by post hoc Bonferroni was used to analyze data (p < 0.05). Within 15 min of MO (but not control) pulp application, RAD thresholds increased significantly (p < 0.001) as compared to baseline. One hour following MSO (but not saline) application to the face-M1, RAD thresholds decreased significantly (p = 0.005) toward baseline. These novel findings suggest that acute inflammatory dental pain is associated with decreased face-M1 excitability that may be dependent on the functional integrity of face-M1 astrocytes and related to mechanisms underlying limited jaw movements in acute orofacial pain conditions.

  15. Hyposalivation after undergoing stapedectomy.

    PubMed

    Mandel, Louis

    2012-01-01

    Treatment for otosclerosis involves patients' undergoing stapedectomy. Inadvertent damage to the chorda tympani nerve's (CTN's) secretory fibers during stapedectomy can result in inadequate secretory stimulation of the submandibular salivary glands (SMSGs) and sublingual salivary glands (SLSGs). Because most saliva originates from these glands, hyposalivation and subjective xerostomia manifest during resting periods when parotid gland secretions are minimal. Stimulation with food increases parotid gland salivation enough to overcome the subjective sense of dryness. The author examined a 52-year-old man who had undergone bilateral stapedectomy because of hearing loss; his rheumatologist referred him to the Salivary Gland Center (New York City) because of a complaint of dry mouth. After the author examined the patient, he concluded that the patient had decreased SMSG and SLSG secretion and recommended that the patient use sugarless chewing gum or sour candy frequently to stimulate his parotid glands and use oral lubricants and sip water as needed. Stimulation of parotid gland secretion is independent of SMSG and SLSG activation. Therefore, the dental practitioner must become aware of the innervation of the salivary glands and each gland's secretory production during periods of oral stimulation and of rest.

  16. Ovarian cortex cryopreservation in pediatric and adolescent medicine

    PubMed

    Revel; Davis; Casper

    2000-05-01

    Background: Increased pediatric/adolescent cancer survivor rates have enhanced awareness of long-term effects of therapy, specifically gonadal failure. Ovarian cortex cryopreservation may hold the promise of fertility for those at risk for ovarian failure due to medical therapy. The object of this study was to determine if an ovarian cryopreservation program is feasible and to define suitable candidates.Method: A MEDLINE search supplemented by bibliographies. The review was limited to English articles on ovarian failure rates following radiation and/or chemotherapy and on ovarian cryopreservation. Investigators in the field were consulted to identify other sources.Results: Approximately one third of postpubertal females exposed to chemotherapy or radiotherapy develop ovarian failure. The risk is mostly significant for patients exposed to pelvic radiotherapy (up to 32% decrease in fertility) and alkylating agent based chemotherapy (infertility in 22%). A ninefold increase in premature ovarian failure results from exposure to combined pelvic radiotherapy and alkylator based chemotherapy. Practically all patients exposed to multiple agent chemotherapy combined with pelvic radiotherapy at doses used in preparation for bone marrow transplant will undergo irreversible loss of ovarian function. Currently human ovarian cortex can be cryopreserved, thawed and stimulated with gonadotrophins to produce follicles when transplanted into immunosuppressed mice, however there has yet to be any human pregnancies. The immunosupressed mouse model could also serve as a test to determine whether the tissue carries metastatic risk prior to reimplantation into the donor.Conclusion: Based on the literature we propose ovarian cortex cryopreservation and banking for postpubertal females prior to chemotherapy and/or radiation therapy that holds a high risk of ovarian failure. In the future this may provide oocytes for reproductive purposes. A protocol is currently under approval by the

  17. Changes in Cerebral Cortex of Children Treated for Medulloblastoma

    SciTech Connect

    Liu, Arthur K. . E-mail: aliu1@partners.org; Marcus, Karen J.; Fischl, Bruce; Grant, P. Ellen; Young Poussaint, Tina; Rivkin, Michael J.; Davis, Peter; Tarbell, Nancy J.; Yock, Torunn I.

    2007-07-15

    Purpose: Children with medulloblastoma undergo surgery, radiotherapy, and chemotherapy. After treatment, these children have numerous structural abnormalities. Using high-resolution magnetic resonance imaging, we measured the thickness of the cerebral cortex in a group of medulloblastoma patients and a group of normally developing children. Methods and Materials: We obtained magnetic resonance imaging scans and measured the cortical thickness in 9 children after treatment of medulloblastoma. The measurements from these children were compared with the measurements from age- and gender-matched normally developing children previously scanned. For additional comparison, the pattern of thickness change was compared with the cortical thickness maps from a larger group of 65 normally developing children. Results: In the left hemisphere, relatively thinner cortex was found in the perirolandic region and the parieto-occipital lobe. In the right hemisphere, relatively thinner cortex was found in the parietal lobe, posterior superior temporal gyrus, and lateral temporal lobe. These regions of cortical thinning overlapped with the regions of cortex that undergo normal age-related thinning. Conclusion: The spatial distribution of cortical thinning suggested that the areas of cortex that are undergoing development are more sensitive to the effects of treatment of medulloblastoma. Such quantitative methods may improve our understanding of the biologic effects that treatment has on the cerebral development and their neuropsychological implications.

  18. Decreased prefrontal cortical dopamine transmission in alcoholism.

    PubMed

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

    2014-08-01

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

  19. Elastic instabilities in a model cerebral cortex

    NASA Astrophysics Data System (ADS)

    Mayett, David; Manyuhina, Oksana; Schwarz, J. M.

    2014-03-01

    Soft and biological systems exhibit elastic instabilities, such as buckling, folding and wrinkling, in the presence of external loads, growth, or both. The modeling of such systems calls for a continuum approach to account for the interplay between local elastic stresses and global growth profiles. It is this interplay that can lead to non-trivial geometries. We propose a model of the cerebral cortex, described as an anisotropic multi-layered material with two basic components (white matter and grey matter) undergoing differential growth. We explore the nature of buckling instabilities, assuming a compatibility between the growth and geometric deformation, by solving a nonlinear variational problem with a free interface. We expect that this simplified approach, based on a combination of geometry and elasticity, could give insight into the formation and splitting of folds observed during the development of the cerebral cortex.

  20. Auditory cortex involvement in emotional learning and memory.

    PubMed

    Grosso, A; Cambiaghi, M; Concina, G; Sacco, T; Sacchetti, B

    2015-07-23

    Emotional memories represent the core of human and animal life and drive future choices and behaviors. Early research involving brain lesion studies in animals lead to the idea that the auditory cortex participates in emotional learning by processing the sensory features of auditory stimuli paired with emotional consequences and by transmitting this information to the amygdala. Nevertheless, electrophysiological and imaging studies revealed that, following emotional experiences, the auditory cortex undergoes learning-induced changes that are highly specific, associative and long lasting. These studies suggested that the role played by the auditory cortex goes beyond stimulus elaboration and transmission. Here, we discuss three major perspectives created by these data. In particular, we analyze the possible roles of the auditory cortex in emotional learning, we examine the recruitment of the auditory cortex during early and late memory trace encoding, and finally we consider the functional interplay between the auditory cortex and subcortical nuclei, such as the amygdala, that process affective information. We conclude that, starting from the early phase of memory encoding, the auditory cortex has a more prominent role in emotional learning, through its connections with subcortical nuclei, than is typically acknowledged. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Neuropsychology of prefrontal cortex

    PubMed Central

    Siddiqui, Shazia Veqar; Chatterjee, Ushri; Kumar, Devvarta; Siddiqui, Aleem; Goyal, Nishant

    2008-01-01

    The history of clinical frontal lobe study is long and rich which provides valuable insights into neuropsychologic determinants of functions of prefrontal cortex (PFC). PFC is often classified as multimodal association cortex as extremely processed information from various sensory modalities is integrated here in a precise fashion to form the physiologic constructs of memory, perception, and diverse cognitive processes. Human neuropsychologic studies also support the notion of different functional operations within the PFC. The specification of the component ‘executive’ processes and their localization to particular regions of PFC have been implicated in a wide variety of psychiatric disorders. PMID:19742233

  2. The Age of Human Cerebral Cortex Neurons

    SciTech Connect

    Bhardwaj, R D; Curtis, M A; Spalding, K L; Buchholz, B A; Fink, D; Bjork-Eriksson, T; Nordborg, C; Gage, F H; Druid, H; Eriksson, P S; Frisen, J

    2006-04-06

    The traditional static view of the adult mammalian brain has been challenged by the realization of continuous generation of neurons from stem cells. Based mainly on studies in experimental animals, adult neurogenesis may contribute to recovery after brain insults and decreased neurogenesis has been implicated in the pathogenesis of neurological and psychiatric diseases in man. The extent of neurogenesis in the adult human brain has, however, been difficult to establish. We have taken advantage of the integration of {sup 14}C, generated by nuclear bomb tests during the Cold War, in DNA to establish the age of neurons in the major areas of the human cerebral cortex. Together with the analysis of the cortex from patients who received BrdU, which integrates in the DNA of dividing cells, our results demonstrate that whereas non-neuronal cells turn over, neurons in the human cerebral cortex are not generated postnatally at detectable levels, but are as old as the individual.

  3. Differential Modification of Cortical and Thalamic Projections to Cat Primary Auditory Cortex Following Early- and Late-Onset Deafness.

    PubMed

    Chabot, Nicole; Butler, Blake E; Lomber, Stephen G

    2015-10-15

    Following sensory deprivation, primary somatosensory and visual cortices undergo crossmodal plasticity, which subserves the remaining modalities. However, controversy remains regarding the neuroplastic potential of primary auditory cortex (A1). To examine this, we identified cortical and thalamic projections to A1 in hearing cats and those with early- and late-onset deafness. Following early deafness, inputs from second auditory cortex (A2) are amplified, whereas the number originating in the dorsal zone (DZ) decreases. In addition, inputs from the dorsal medial geniculate nucleus (dMGN) increase, whereas those from the ventral division (vMGN) are reduced. In late-deaf cats, projections from the anterior auditory field (AAF) are amplified, whereas those from the DZ decrease. Additionally, in a subset of early- and late-deaf cats, area 17 and the lateral posterior nucleus (LP) of the visual thalamus project concurrently to A1. These results demonstrate that patterns of projections to A1 are modified following deafness, with statistically significant changes occurring within the auditory thalamus and some cortical areas. Moreover, we provide anatomical evidence for small-scale crossmodal changes in projections to A1 that differ between early- and late-onset deaf animals, suggesting that potential crossmodal activation of primary auditory cortex differs depending on the age of deafness onset.

  4. Anterior insular cortex is necessary for empathetic pain perception

    PubMed Central

    Gu, Xiaosi; Gao, Zhixian; Wang, Xingchao; Liu, Xun; Knight, Robert T.; Hof, Patrick R.

    2012-01-01

    Empathy refers to the ability to perceive and share another person’s affective state. Much neuroimaging evidence suggests that observing others’ suffering and pain elicits activations of the anterior insular and the anterior cingulate cortices associated with subjective empathetic responses in the observer. However, these observations do not provide causal evidence for the respective roles of anterior insular and anterior cingulate cortices in empathetic pain. Therefore, whether these regions are ‘necessary’ for empathetic pain remains unknown. Herein, we examined the perception of others’ pain in patients with anterior insular cortex or anterior cingulate cortex lesions whose locations matched with the anterior insular cortex or anterior cingulate cortex clusters identified by a meta-analysis on neuroimaging studies of empathetic pain perception. Patients with focal anterior insular cortex lesions displayed decreased discrimination accuracy and prolonged reaction time when processing others’ pain explicitly and lacked a typical interference effect of empathetic pain on the performance of a pain-irrelevant task. In contrast, these deficits were not observed in patients with anterior cingulate cortex lesions. These findings reveal that only discrete anterior insular cortex lesions, but not anterior cingulate cortex lesions, result in deficits in explicit and implicit pain perception, supporting a critical role of anterior insular cortex in empathetic pain processing. Our findings have implications for a wide range of neuropsychiatric illnesses characterized by prominent deficits in higher-level social functioning. PMID:22961548

  5. Normalization in human somatosensory cortex.

    PubMed

    Brouwer, Gijs Joost; Arnedo, Vanessa; Offen, Shani; Heeger, David J; Grant, Arthur C

    2015-11-01

    Functional magnetic resonance imaging (fMRI) was used to measure activity in human somatosensory cortex and to test for cross-digit suppression. Subjects received stimulation (vibration of varying amplitudes) to the right thumb (target) with or without concurrent stimulation of the right middle finger (mask). Subjects were less sensitive to target stimulation (psychophysical detection thresholds were higher) when target and mask digits were stimulated concurrently compared with when the target was stimulated in isolation. fMRI voxels in a region of the left postcentral gyrus each responded when either digit was stimulated. A regression model (called a forward model) was used to separate the fMRI measurements from these voxels into two hypothetical channels, each of which responded selectively to only one of the two digits. For the channel tuned to the target digit, responses in the left postcentral gyrus increased with target stimulus amplitude but were suppressed by concurrent stimulation to the mask digit, evident as a shift in the gain of the response functions. For the channel tuned to the mask digit, a constant baseline response was evoked for all target amplitudes when the mask was absent and responses decreased with increasing target amplitude when the mask was concurrently presented. A computational model based on divisive normalization provided a good fit to the measurements for both mask-absent and target + mask stimulation. We conclude that the normalization model can explain cross-digit suppression in human somatosensory cortex, supporting the hypothesis that normalization is a canonical neural computation.

  6. [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.

  7. Brain cortex mitochondrial bioenergetics in synaptosomes and non-synaptic mitochondria during aging.

    PubMed

    Lores-Arnaiz, Silvia; Lombardi, Paulina; Karadayian, Analía G; Orgambide, Federico; Cicerchia, Daniela; Bustamante, Juanita

    2016-02-01

    Alterations in mitochondrial bioenergetics have been associated with brain aging. In order to evaluate the susceptibility of brain cortex synaptosomes and non-synaptic mitochondria to aging-dependent dysfunction, male Swiss mice of 3 or 17 months old were used. Mitochondrial function was evaluated by oxygen consumption, mitochondrial membrane potential and respiratory complexes activity, together with UCP-2 protein expression. Basal respiration and respiration driving proton leak were decreased by 26 and 33 % in synaptosomes from 17-months old mice, but spare respiratory capacity was not modified by aging. Succinate supported state 3 respiratory rate was decreased by 45 % in brain cortex non-synaptic mitochondria from 17-month-old mice, as compared with young animals, but respiratory control was not affected. Synaptosomal mitochondria would be susceptible to undergo calcium-induced depolarization in 17 months-old mice, while non-synaptic mitochondria would not be affected by calcium overload. UCP-2 was significantly up-regulated in both synaptosomal and submitochondrial membranes from 17-months old mice, compared to young animals. UCP-2 upregulation seems to be a possible mechanism by which mitochondria would be resistant to suffer oxidative damage during aging.

  8. THE VISUAL CORTEX, ITS LOCALIZATION, HISTOLOGICAL STRUCTURE, AND PHYSIOLOGICAL FUNCTION.

    PubMed

    Funkhouser, E B

    1915-06-01

    In the study of the human cortex it seems well to follow the same primary divisions for the entire cortex, while in certain areas some layers may assume certain modifications; viz., in the area striata it seems clearer to retain the sixth layer ground type, of which the fourth is subdivided into three secondary layers. The visual cortex, on account of its relation to the act of seeing, is an especially interesting field for study. About the calcarine fissure one can readily see with the naked eye a stripe of white fibers lying in the gray substance, called stria of Gennari or of Vicq-d' Azyr. This layer is considered by Brodmann in the second subdivision of the fourth primary layer. The two most characteristic types of the cortex are the giant pyramid type, called area gigantopyramidalis, and the calcarine type, called area striata. The higher types of mammals afford excellent material for comparison. Minkowski's experimental study of the dog indicates that the clinical, anatomical visual sphere is covered with the cytoarchitectonic sphere; for lasting visual trouble can be caused only by extirpation of the area striata. The subcortical visual center in mammals undergoes secondary degeneration through destruction of the area striata, and therefore depends on the cortex. Also certain parts of the corpus geniculatum externum have an exact projection over certain areas of the cortex.

  9. CX-516 Cortex pharmaceuticals.

    PubMed

    Danysz, Wojciech

    2002-07-01

    CX-516 is one of a series of AMPA modulators under development by Cortex, in collaboration with Shire and Servier, for the potential treatment of Alzheimer's disease (AD), schizophrenia and mild cognitive impairment (MCI) [234221]. By June 2001, CX-516 was in phase II trials for both schizophrenia and attention deficit hyperactivity disorder (ADHD) [412513]. A phase II trial in fragile X syndrome and autism was expected to start in May 2002 [449861]. In October 2001, Cortex was awarded a Phase II SBIR grant of $769,818 from the National Institutes of Mental Health to investigate the therapeutic potential of AMPAkines in schizophrenia. This award was to support a phase IIb study of CX-516 as a combination therapy in schizophrenia patients concomitantly treated with olanzapine. The trial was to enroll 80 patients and employ a randomized, double-blind, placebo-controlled design in which the placebo group was to receive olanzapine plus placebo and the active group was to receive olanzapine plus CX-516 [425982]. In April 2000, Shire and Cortex signed an option agreement in which Shire was to evaluate CX-516for the treatment of ADHD. Under the terms of the agreement, Shire would undertake a double-blind, placebo-controlled evaluation of CX-516 involving ADHD patients. If the study proved effective, Shire would have the right to convert its option into an exclusive worldwide license for the AMPAkines for ADHD under a development and licensing agreement. Should Shire elect to execute this agreement, Shire would bear all future developmental costs [363618]. By February 2002, Cortex and Servier had revealed their intention to begin enrolment for an international study of an AMPAkine compound as a potential treatment for MCI in the near future. Assuming enrollment proceeded as anticipated, results were expected during the second quarter of 2003 [439301]. By May 2002, phase II trials were underway [450134]. In March 2002, Cortex was awarded extended funding under the

  10. Diazepam reduces excitability of amygdala and further influences auditory cortex following sodium salicylate treatment in rats.

    PubMed

    Song, Yu; Liu, Junxiu; Ma, Furong; Mao, Lanqun

    2016-12-01

    Diazepam can reduce the excitability of lateral amygdala and eventually suppress the excitability of the auditory cortex in rats following salicylate treatment, indicating the regulating effect of lateral amygdala to the auditory cortex in the tinnitus procedure. To study the spontaneous firing rates (SFR) of the auditory cortex and lateral amygdala regulated by diazepam in the tinnitus rat model induced by sodium salicylate. This study first created a tinnitus rat modal induced by sodium salicylate, and recorded SFR of both auditory cortex and lateral amygdala. Then diazepam was intraperitoneally injected and the SFR changes of lateral amygdala recorded. Finally, diazepam was microinjected on lateral amygdala and the SFR changes of the auditory cortex recorded. Both SFRs of the auditory cortex and lateral amygdala increased after salicylate treatment. SFR of lateral amygdala decreased after intraperitoneal injection of diazepam. Microinjecting diazepam to lateral amygdala decreased SFR of the auditory cortex ipsilaterally and contralaterally.

  11. Anterior thalamic lesions produce chronic and profuse transcriptional de-regulation in retrosplenial cortex: A model of retrosplenial hypoactivity and covert pathology

    PubMed Central

    Poirier, G.L.; Shires, K.L.; Sugden, D.; Amin, E.; Thomas, K.L.; Carter, D.A.; Aggleton, J.P.

    2010-01-01

    Anterior thalamic lesions are thought to produce ‘covert pathology’ in retrosplenial cortex, but the causes are unknown. Microarray analyses tested the hypothesis that thalamic damage causes a chronic, hypo-function of metabolic and plasticity-related pathways (Experiment 1). Rats with unilateral, anterior thalamic lesions were exposed to a novel environment for 20 minutes, and granular retrosplenial tissue sampled from both hemispheres 30 minutes, 2h, or 8h later. Complementary statistical approaches (analyses of variance, predictive patterning and gene set enrichment analysis) revealed pervasive gene expression differences between retrosplenial cortex ipsilateral to the thalamic lesion and contralateral to the lesion. Selected gene differences were validated by QPCR, immunohistochemistry (Experiment 1), and in situ hybridisation (Experiment 2). Following thalamic lesions, the retrosplenial cortex undergoes profuse cellular transcriptome changes including lower relative levels of specific mRNAs involved in energy metabolism and neuronal plasticity. These changes in functional gene expression may be largely driven by decreases in the expression of multiple transcription factors, including brd8, c-fos, fra-2, klf5, nfix, nr4a1, smad3, smarcc2, and zfp9, with a much smaller number (nfat5, neuroD1, RXRγ) showing increases. These findings have implications for conditions such as diencephalic amnesia and Alzheimer’s disease, where both anterior thalamic pathology and retrosplenial cortex hypometabolism are prominent. PMID:21289865

  12. Aging somatosensory cortex displays increased density of WFA-binding perineuronal nets associated with GAD-negative neurons.

    PubMed

    Karetko-Sysa, M; Skangiel-Kramska, J; Nowicka, D

    2014-09-26

    The mechanisms of aging in the brain and the subsequent decrease in cognitive abilities remain elusive. While most studies refer to research conducted in old and senile animals, little is known about the early symptoms of normal, healthy aging. In this study, we examined whether perineuronal nets (PNNs), a special form of extracellular matrix (ECM) tightly associated with neurons that is thought to be involved in limiting neuronal plasticity, undergo changes in density during early aging. Using histochemistry and immunohistochemistry, we found that in middle-aged mice (1-year-old), the density of WFA-binding PNNs in the somatosensory cortex as well as in the visual cortex was increased in comparison to that in young adults (3-month-old). Moreover, in the somatosensory cortex, this increase was not associated with any of the GABAergic neuron types that were examined. We propose that early age-related changes in neuronal plasticity may be associated with this increase and can be conceptualized as the spreading of structural brakes for synaptic rearrangements.

  13. Motor cortex changes in spinal cord injury: a TMS study.

    PubMed

    Saturno, Eleonora; Bonato, Claudio; Miniussi, Carlo; Lazzaro, Vincenzodi; Callea, Leonardo

    2008-12-01

    Using paired pulse transcranial magnetic stimulation (TMS) paradigms, we studied cortical excitability in a patient with spinal cord lesion. During posterior tibial nerve stimulation, the contextual flexion of hand fingers contralateral to the stimulated lower limb had suggested a change in motor cortex excitability. Results showed a decrease in the activity of motor cortex inhibitory circuits. This could suggest that in spinal cord injury, just as in stroke and peripheral deafferentation, a disinhibition of latent synapses within the motor cortex and the rewriting of a new motor map can occur.

  14. Neurocontrol in sensory cortex

    NASA Astrophysics Data System (ADS)

    Ritt, Jason; Nandi, Anirban; Schroeder, Joseph; Ching, Shinung

    Technology to control neural ensembles is rapidly advancing, but many important challenges remain in applications, such as design of controls (e.g. stimulation patterns) with specificity comparable to natural sensory encoding. We use the rodent whisker tactile system as a model for active touch, in which sensory information is acquired in a closed loop between feedforward encoding of sensory information and feedback guidance of sensing motions. Motivated by this system, we present optimal control strategies that are tailored for underactuation (a large ratio of neurons or degrees of freedom to stimulation channels) and limited observability (absence of direct measurement of the system state), common in available stimulation technologies for freely behaving animals. Using a control framework, we have begun to elucidate the feedback effect of sensory cortex activity on sensing in behaving animals. For example, by optogenetically perturbing primary sensory cortex (SI) activity at varied timing relative to individual whisker motions, we find that SI modulates future sensing behavior within 15 msec, on a whisk by whisk basis, changing the flow of incoming sensory information based on past experience. J.T.R. and S.C. hold Career Awards at the Scientific Interface from the Burroughs Wellcome Fund.

  15. Distraction decreases prefrontal oxygenation: A NIRS study.

    PubMed

    Ozawa, Sachiyo; Hiraki, Kazuo

    2017-04-01

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

  16. Aging, self-referencing, and medial prefrontal cortex.

    PubMed

    Gutchess, Angela H; Kensinger, Elizabeth A; Schacter, Daniel L

    2007-01-01

    The lateral prefrontal cortex undergoes both structural and functional changes with healthy aging. In contrast, there is little structural change in the medial prefrontal cortex, but relatively little is known about the functional changes to this region with age. Using an event-related fMRI design, we investigated the response of medial prefrontal cortex during self-referencing in order to compare age groups on a task that young and elderly perform similarly and that is known to actively engage the region in young adults. Nineteen young (M age = 23) and seventeen elderly (M age = 72) judged whether adjectives described themselves, another person, or were presented in upper case. We assessed the overlap in activations between young and elderly for the self-reference effect (self vs. other person), and found that both groups engage medial prefrontal cortex and mid-cingulate during self-referencing. The only cerebral differences between the groups in self versus other personality assessment were found in somatosensory and motor-related areas. In contrast, age-related modulations were found in the cerebral network recruited for emotional valence processing. Elderly (but not young) showed increased activity in the dorsal prefrontal cortex for positive relative to negative items, which could reflect an increase in controlled processing of positive information for elderly adults.

  17. Study of the human visual cortex: direct cortical evoked potentials and stimulation.

    PubMed

    Farrell, Donald F; Leeman, Stephanie; Ojemann, George A

    2007-02-01

    The authors studied the visual cortex of 15 patients undergoing studies for medically intractable epilepsy. Although the subdural and strip electrode placement varied in each of these patients, there were enough electrodes over the visual cortex to complete studies involving evoked potentials and direct cortical stimulation. Visual evoked potentials were elicited using two check sizes (50 and 16 min) for pattern reversal studies, 50 min checks for on-off stimulation, 50 min checks for horizontal and vertical hemifields and simple flash for the VEP. These studies demonstrated that the pattern reversal and on-off stimuli caused very complex, multipotential waveforms in striate and vision associational cortex that do not resemble the response obtained at the scalp. Different volumes of visual cortex are activated by stimulation with 16 min checks, 50 min checks and simple flash. Flash activates the largest volume of visual cortex and it is likely that this finding is what makes this test of so little value clinically. Direct cortical stimulation shows that colored responses are generated primarily in the posterior striate cortex and inferior occipital lobe, while movement is primarily generated by the visual association cortex. No complex visual images were obtained by stimulation of either the striate cortex or visual association cortex. The brain mechanisms that lead to formed visual images remain to be identified.

  18. Adrenal cortex dysfunction: CT findings

    SciTech Connect

    Huebener, K.H.; Treugut, H.

    1984-01-01

    The computed tomographic appearance of the adrenal gland was studied in 302 patients with possible endocrinologic disease and 107 patients undergoing CT for nonendocrinologic reasons. Measurements of adrenal size were also made in 100 adults with no known adrenal pathology. CT proved to be a sensitive diagnostic tool in combination with clinical studies. When blood hormone levels are increased, CT can differentiate among homogeneous organic hyperplasia, nodular hyperplasia, benign adenoma, and malignant cortical adenoma. When blood hormone levels are decreased, CT can demonstrate hypoplasia or metastatic tumorous destruction. Calcifications can be demonstrated earlier than on plain radiographs. When hormone elimination is increased, the morphologic substrate can be identified; tumorous changes can be localized and infiltration of surrounding organs recognized.

  19. Word Recognition in Auditory Cortex

    ERIC Educational Resources Information Center

    DeWitt, Iain D. J.

    2013-01-01

    Although spoken word recognition is more fundamental to human communication than text recognition, knowledge of word-processing in auditory cortex is comparatively impoverished. This dissertation synthesizes current models of auditory cortex, models of cortical pattern recognition, models of single-word reading, results in phonetics and results in…

  20. Word Recognition in Auditory Cortex

    ERIC Educational Resources Information Center

    DeWitt, Iain D. J.

    2013-01-01

    Although spoken word recognition is more fundamental to human communication than text recognition, knowledge of word-processing in auditory cortex is comparatively impoverished. This dissertation synthesizes current models of auditory cortex, models of cortical pattern recognition, models of single-word reading, results in phonetics and results in…

  1. Adrenal cortex ontogenesis.

    PubMed

    Lalli, Enzo

    2010-12-01

    During the early phases of development, adrenal glands share a common origin with kidneys and gonads. The action of diverse transcription factors, signalling pathways and endocrine signals is required for the individualization of the adrenal primordium and its subsequent differentiation into an adult adrenal gland, with massive remodelling taking place around the time of birth in humans. Here I summarize the most important steps by which the adrenal cortex is shaped and present an overview of the current understanding of the genes and molecular pathways implicated in adrenal development and involved in the pathogenesis of its congenital diseases. Evidence is accumulating that some pivotal factors acting during adrenocortical development also play an important role to regulate the growth of adrenocortical tumors, representing promising therapeutical targets for a biology-oriented therapy. 2010 Elsevier Ltd. All rights reserved.

  2. Evolution of neuronal and astroglial disruption in the peri-contusional cortex of mice revealed by in vivo two-photon imaging

    PubMed Central

    Masuda, Tadashi; Croom, Deborah

    2013-01-01

    In traumatic brain injury mechanical forces applied to the cranium and brain cause irreversible primary neuronal and astroglial damage associated with terminal dendritic beading and spine loss representing acute damage to synaptic circuitry. Oedema develops quickly after trauma, raising intracranial pressure that results in a decrease of blood flow and consequently in cerebral ischaemia, which can cause secondary injury in the peri-contusional cortex. Spreading depolarizations have also been shown to occur after traumatic brain injury in humans and in animal models and are thought to accelerate and exacerbate secondary tissue injury in at-risk cortical territory. Yet, the mechanisms of acute secondary injury to fine synaptic circuitry within the peri-contusional cortex after mild traumatic brain injury remain unknown. A mild focal cortical contusion model in adult mouse sensory-motor cortex was implemented by the controlled cortical impact injury device. In vivo two-photon microscopy in the peri-contusional cortex was used to monitor via optical window yellow fluorescent protein expressing neurons, enhanced green fluorescent protein expressing astrocytes and capillary blood flow. Dendritic beading in the peri-contusional cortex developed slowly and the loss of capillary blood flow preceded terminal dendritic injury. Astrocytes were swollen indicating oedema and remained swollen during the next 24 h throughout the imaging session. There were no recurrent spontaneous spreading depolarizations in this mild traumatic brain injury model; however, when spreading depolarizations were repeatedly induced outside the peri-contusional cortex by pressure-injecting KCl, dendrites undergo rapid beading and recovery coinciding with passage of spreading depolarizations, as was confirmed with electrophysiological recordings in the vicinity of imaged dendrites. Yet, accumulating metabolic stress resulting from as few as four rounds of spreading depolarization significantly added to

  3. Decreased subcortical cholinergic arousal in focal seizures

    PubMed Central

    Motelow, Joshua E.; Li, Wei; Zhan, Qiong; Mishra, Asht M.; Sachdev, Robert N. S.; Liu, Geoffrey; Gummadavelli, Abhijeet; Zayyad, Zaina; Lee, Hyun Seung; Chu, Victoria; Andrews, John P.; Englot, Dario J.; Herman, Peter; Sanganahalli, Basavaraju G.; Hyder, Fahmeed; Blumenfeld, Hal

    2015-01-01

    SUMMARY Impaired consciousness in temporal lobe seizures has a major negative impact on quality of life. The prevailing view holds that this disorder impairs consciousness by seizure spread to the bilateral temporal lobes. We propose instead that seizures invade subcortical regions and depress arousal, causing impairment through decreases rather than through increases in activity. Using functional magnetic resonance imaging in a rodent model, we found increased activity in regions known to depress cortical function including lateral septum and anterior hypothalamus. Importantly, we found suppression of intralaminar thalamic and brainstem arousal systems and suppression of the cortex. At a cellular level, we found reduced firing of identified cholinergic neurons in the brainstem pedunculopontine tegmental nucleus and basal forebrain. Finally, we used enzyme-based amperometry to demonstrate reduced cholinergic neurotransmission in both cortex and thalamus. Decreased subcortical arousal is a novel mechanism for loss of consciousness in focal temporal lobe seizures. PMID:25654258

  4. The human cerebral cortex flattens during adolescence.

    PubMed

    Alemán-Gómez, Yasser; Janssen, Joost; Schnack, Hugo; Balaban, Evan; Pina-Camacho, Laura; Alfaro-Almagro, Fidel; Castro-Fornieles, Josefina; Otero, Soraya; Baeza, Immaculada; Moreno, Dolores; Bargalló, Nuria; Parellada, Mara; Arango, Celso; Desco, Manuel

    2013-09-18

    The human cerebral cortex appears to shrink during adolescence. To delineate the dynamic morphological changes involved in this process, 52 healthy male and female adolescents (11-17 years old) were neuroimaged twice using magnetic resonance imaging, approximately 2 years apart. Using a novel morphometric analysis procedure combining the FreeSurfer and BrainVisa image software suites, we quantified global and lobar change in cortical thickness, outer surface area, the gyrification index, the average Euclidean distance between opposing sides of the white matter surface (gyral white matter thickness), the convex ("exposed") part of the outer cortical surface (hull surface area), sulcal length, depth, and width. We found that the cortical surface flattens during adolescence. Flattening was strongest in the frontal and occipital cortices, in which significant sulcal widening and decreased sulcal depth co-occurred. Globally, sulcal widening was associated with cortical thinning and, for the frontal cortex, with loss of surface area. For the other cortical lobes, thinning was related to gyral white matter expansion. The overall flattening of the macrostructural three-dimensional architecture of the human cortex during adolescence thus involves changes in gray matter and effects of the maturation of white matter.

  5. Epidural motor cortex stimulation suppresses somatosensory evoked potentials in the primary somatosensory cortex of the rat.

    PubMed

    Chiou, Ruei-Jen; Lee, Hsiao-Yun; Chang, Chen-Wei; Lin, Kuan-Hung; Kuo, Chung-Chih

    2012-06-29

    Motor cortex stimulation (MCS) is a promising clinical procedure to help alleviate chronic pain. Animal models demonstrated that MCS is effective in lessening nocifensive behaviors. The present study explored the effects of MCS on cortical somatosensory evoked potentials (SEPs) recorded at the primary somatosensory cortex (SI) of the rat. SEPs were evoked by electrical stimulation applied to the contralateral forepaws. Effects of different intensities, frequencies, and durations of MCS were tested. MCS at ≥2V suppressed SEPs of the ipsilateral SI. Suppression lasted 120 min at an intensity of 5 V. The optimal frequency was 50 Hz, and the duration was 30s. In contrast, MCS did not affect SEPs recorded on the contralateral SI. Cortical stimulation out of the motor cortex did not induce a decrease in the ipsilateral SEPs. We also investigated involvement of the endogenous opioid system in this inhibition of SEPs induced by MCS. The opioid antagonist, naloxone (0.5 mg/kg), was administered 30 min before MCS. Application of naloxone completely prevented the inhibitory effect of MCS on ipsilateral SEPs. These results demonstrate that MCS blocked the transmission of somatosensory information to the primary somatosensory cortex, and this interference was mediated by the endogenous opioid system. This inhibitory effect on sensory transmission induced by MCS may reflect its antinociceptive effect.

  6. Reduced inhibition within primary motor cortex in patients with poststroke focal motor seizures.

    PubMed

    Kessler, Kirn R; Schnitzler, Alfons; Classen, Joseph; Benecke, Reiner

    2002-10-08

    Following an ischemic brain lesion, the affected cortex undergoes structural and functional changes that may lead to increased cortical excitability or decreased inhibitory neuronal activity, resulting in the occurrence of poststroke epileptic seizures in 6 to 10% of patients with stroke. To assess motor cortical excitability, transcranial magnetic stimulation (TMS) was used to determine the silent period (SP) duration in 84 consecutive patients with ischemic stroke. In a subpopulation of six patients (38 to 72 years old) a significant decrease of the SP duration (mean 116 +/- 14 msec) was detected in either the arm or the leg on the affected side as compared to the corresponding unaffected limb (mean 231 +/- 32 msec). This electrophysiologic abnormality was clinically associated with focal motor seizures in five of the six patients, whereas none of the other 76 patients with normal or prolonged SP durations developed seizures or epilepsy. Silent period shortening in this group reflects decreased inhibitory activity that may partly be related to functional or structural impairment of GABAergic interneurons. TMS may be of value for determining patients with stroke at risk for developing poststroke seizures.

  7. Prefrontal cortical dopamine transmission is decreased in alcoholism

    PubMed Central

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

    2014-01-01

    Objective Basic studies have demonstrated that optimal levels of prefrontal cortical dopamine are critical to various executive functions such working memory, attention, inhibitory control and risk/reward decisions--all of which are impaired in addictive disorders such as alcoholism. Based on this and imaging studies in alcoholics that have demonstrated less dopamine in the striatum, we hypothesized decreased dopamine transmission in the prefrontal cortex in alcoholism. To test this hypothesis, we used amphetamine and [11C]FLB 457 positron emission tomography (PET) to measure cortical dopamine transmission in a group of 21 recently abstinent alcoholics and matched healthy controls. Methods [11C]FLB 457 binding potential (BPND) was measured in subjects with kinetic analysis using the arterial input function both before and after 0.5 mg kg−1 of d-amphetamine. Results Amphetamine-induced displacement of [11C]FLB 457 binding potential (Δ BPND) was significantly smaller in the cortical regions in alcoholics compared to healthy controls. Cortical regions that demonstrated lower dopamine transmission in alcoholics included the dorsolateral prefrontal cortex, medial prefrontal cortex, orbital frontal cortex, temporal cortex and medial temporal lobe. Conclusions The results of this study for the first time unambiguously demonstrate decreased dopamine transmission in the cortex in alcoholism. Further research is necessary to understand the clinical relevance of decreased cortical dopamine as to whether it is related to impaired executive function, relapse, and outcome in alcoholism. PMID:24874293

  8. Chemosensory Learning in the Cortex

    PubMed Central

    Rolls, Edmund T.

    2011-01-01

    Taste is a primary reinforcer. Olfactory–taste and visual–taste association learning takes place in the primate including human orbitofrontal cortex to build representations of flavor. Rapid reversal of this learning can occur using a rule-based learning system that can be reset when an expected taste or flavor reward is not obtained, that is by negative reward prediction error, to which a population of neurons in the orbitofrontal cortex responds. The representation in the orbitofrontal cortex but not the primary taste or olfactory cortex is of the reward value of the visual/olfactory/taste input as shown by devaluation experiments in which food is fed to satiety, and by correlations of the activations with subjective pleasantness ratings in humans. Sensory-specific satiety for taste, olfactory, visual, and oral somatosensory inputs produced by feeding a particular food to satiety is implemented it is proposed by medium-term synaptic adaptation in the orbitofrontal cortex. Cognitive factors, including word-level descriptions, modulate the representation of the reward value of food in the orbitofrontal cortex, and this effect is learned it is proposed by associative modification of top-down synapses onto neurons activated by bottom-up taste and olfactory inputs when both are active in the orbitofrontal cortex. A similar associative synaptic learning process is proposed to be part of the mechanism for the top-down attentional control to the reward value vs. the sensory properties such as intensity of taste and olfactory inputs in the orbitofrontal cortex, as part of a biased activation theory of selective attention. PMID:21954379

  9. Retrieval Is Not Necessary to Trigger Reconsolidation of Object Recognition Memory in the Perirhinal Cortex

    ERIC Educational Resources Information Center

    Santoyo-Zedillo, Marianela; Rodriguez-Ortiz, Carlos J.; Chavez-Marchetta, Gianfranco; Bermudez-Rattoni, Federico; Balderas, Israela

    2014-01-01

    Memory retrieval has been considered as requisite to initiate memory reconsolidation; however, some studies indicate that blocking retrieval does not prevent memory from undergoing reconsolidation. Since N-methyl-D-aspartate (NMDA) and a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors in the perirhinal cortex have…

  10. Retrieval Is Not Necessary to Trigger Reconsolidation of Object Recognition Memory in the Perirhinal Cortex

    ERIC Educational Resources Information Center

    Santoyo-Zedillo, Marianela; Rodriguez-Ortiz, Carlos J.; Chavez-Marchetta, Gianfranco; Bermudez-Rattoni, Federico; Balderas, Israela

    2014-01-01

    Memory retrieval has been considered as requisite to initiate memory reconsolidation; however, some studies indicate that blocking retrieval does not prevent memory from undergoing reconsolidation. Since N-methyl-D-aspartate (NMDA) and a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors in the perirhinal cortex have…

  11. Auditory Cortex Basal Activity Modulates Cochlear Responses in Chinchillas

    PubMed Central

    León, Alex; Elgueda, Diego; Silva, María A.; Hamamé, Carlos M.; Delano, Paul H.

    2012-01-01

    Background The auditory efferent system has unique neuroanatomical pathways that connect the cerebral cortex with sensory receptor cells. Pyramidal neurons located in layers V and VI of the primary auditory cortex constitute descending projections to the thalamus, inferior colliculus, and even directly to the superior olivary complex and to the cochlear nucleus. Efferent pathways are connected to the cochlear receptor by the olivocochlear system, which innervates outer hair cells and auditory nerve fibers. The functional role of the cortico-olivocochlear efferent system remains debated. We hypothesized that auditory cortex basal activity modulates cochlear and auditory-nerve afferent responses through the efferent system. Methodology/Principal Findings Cochlear microphonics (CM), auditory-nerve compound action potentials (CAP) and auditory cortex evoked potentials (ACEP) were recorded in twenty anesthetized chinchillas, before, during and after auditory cortex deactivation by two methods: lidocaine microinjections or cortical cooling with cryoloops. Auditory cortex deactivation induced a transient reduction in ACEP amplitudes in fifteen animals (deactivation experiments) and a permanent reduction in five chinchillas (lesion experiments). We found significant changes in the amplitude of CM in both types of experiments, being the most common effect a CM decrease found in fifteen animals. Concomitantly to CM amplitude changes, we found CAP increases in seven chinchillas and CAP reductions in thirteen animals. Although ACEP amplitudes were completely recovered after ninety minutes in deactivation experiments, only partial recovery was observed in the magnitudes of cochlear responses. Conclusions/Significance These results show that blocking ongoing auditory cortex activity modulates CM and CAP responses, demonstrating that cortico-olivocochlear circuits regulate auditory nerve and cochlear responses through a basal efferent tone. The diversity of the obtained effects

  12. MRI volumetry of prefrontal cortex

    NASA Astrophysics Data System (ADS)

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

    1995-05-01

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

  13. 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

  14. Increased resting state connectivity between ipsilesional motor cortex and contralesional premotor cortex after transcranial direct current stimulation with physical therapy.

    PubMed

    Chen, Joyce L; Schlaug, Gottfried

    2016-03-16

    Non-invasive stimulation of the brain using transcranial direct current stimulation (tDCS) during motor rehabilitation can improve the recovery of movements in individuals with stroke. However, the neural substrates that underlie the clinical improvements are not well understood. In this proof-of-principle open-label pilot study, five individuals with stroke received 10 sessions of tDCS while undergoing usual care physical/occupational therapy for the arm and hand. Motor impairment as indexed by the Upper Extremity Fugl Meyer assessment was significantly reduced after the intervention. Resting state fMRI connectivity increased between ipsilesional motor cortex and contralesional premotor cortex after the intervention. These findings provide preliminary evidence that the neural underpinnings of tDCS coupled with rehabilitation exercises, may be mediated by interactions between motor and premotor cortex. The latter, of which has been shown to play an important role in the recovery of movements post-stroke. Our data suggest premotor cortex could be tested as a target region for non-invasive brain-stimulation to enhance connectivity between regions that might be beneficial for stroke motor recovery.

  15. Increased resting state connectivity between ipsilesional motor cortex and contralesional premotor cortex after transcranial direct current stimulation with physical therapy

    PubMed Central

    Chen, Joyce L; Schlaug, Gottfried

    2016-01-01

    Non-invasive stimulation of the brain using transcranial direct current stimulation (tDCS) during motor rehabilitation can improve the recovery of movements in individuals with stroke. However, the neural substrates that underlie the clinical improvements are not well understood. In this proof-of-principle open-label pilot study, five individuals with stroke received 10 sessions of tDCS while undergoing usual care physical/occupational therapy for the arm and hand. Motor impairment as indexed by the Upper Extremity Fugl Meyer assessment was significantly reduced after the intervention. Resting state fMRI connectivity increased between ipsilesional motor cortex and contralesional premotor cortex after the intervention. These findings provide preliminary evidence that the neural underpinnings of tDCS coupled with rehabilitation exercises, may be mediated by interactions between motor and premotor cortex. The latter, of which has been shown to play an important role in the recovery of movements post-stroke. Our data suggest premotor cortex could be tested as a target region for non-invasive brain-stimulation to enhance connectivity between regions that might be beneficial for stroke motor recovery. PMID:26980052

  16. Electrocorticography Reveals Enhanced Visual Cortex Responses to Visual Speech.

    PubMed

    Schepers, Inga M; Yoshor, Daniel; Beauchamp, Michael S

    2015-11-01

    Human speech contains both auditory and visual components, processed by their respective sensory cortices. We test a simple model in which task-relevant speech information is enhanced during cortical processing. Visual speech is most important when the auditory component is uninformative. Therefore, the model predicts that visual cortex responses should be enhanced to visual-only (V) speech compared with audiovisual (AV) speech. We recorded neuronal activity as patients perceived auditory-only (A), V, and AV speech. Visual cortex showed strong increases in high-gamma band power and strong decreases in alpha-band power to V and AV speech. Consistent with the model prediction, gamma-band increases and alpha-band decreases were stronger for V speech. The model predicts that the uninformative nature of the auditory component (not simply its absence) is the critical factor, a prediction we tested in a second experiment in which visual speech was paired with auditory white noise. As predicted, visual speech with auditory noise showed enhanced visual cortex responses relative to AV speech. An examination of the anatomical locus of the effects showed that all visual areas, including primary visual cortex, showed enhanced responses. Visual cortex responses to speech are enhanced under circumstances when visual information is most important for comprehension.

  17. Visual Cortex Plasticity Following Peripheral Damage To The Visual System: fMRI Evidence.

    PubMed

    Lemos, João; Pereira, Daniela; Castelo-Branco, Miguel

    2016-10-01

    Over the last two decades, functional magnetic resonance imaging (fMRI) has become a powerful research method to investigate cortical visual plasticity. Abnormal fMRI response patterns have been occasionally detected in the visually deprived cortex of patients with bilateral retinal diseases. Controversy remains whether these observations indicate structural reorganization of the visual cortex or unmasking of previously silent cortico-cortical connections. In optic nerve diseases, there is weak evidence showing that early visual cortex seems to lack reorganization, while higher-order visual areas undergo plastic changes which may contribute to optimise visual function. There is however accumulating imaging evidence demonstrating trans-synaptic degeneration of the visual cortex in patients with disease of the anterior visual pathways. This may preclude the use of restorative treatments in these patients. Here, we review and update the body of fMRI evidence on visual cortical plasticity.

  18. The orbitofrontal cortex and emotion in health and disease, including depression.

    PubMed

    Rolls, Edmund T

    2017-09-24

    The orbitofrontal cortex represents the reward or affective value of primary reinforcers including taste, touch, texture, and face expression. It learns to associate other stimuli with these to produce representations of the expected reward value for visual, auditory, and abstract stimuli including monetary reward value. The orbitofrontal cortex thus plays a key role in emotion, by representing the reward value of the goals for action. The learning process is stimulus-reinforcer association learning. Negative reward prediction error neurons are related to this affective learning. Activations in the orbitofrontal cortex correlate with the subjective emotional experience of affective stimuli, and damage to the orbitofrontal cortex impairs emotion-related learning, emotional behaviour, and subjective affective state. Top-down attention to affect modulates orbitofrontal cortex representations, and attention to intensity modulates representations in earlier cortical areas that represent the physical properties of stimuli. Top-down word-level cognitive inputs can bias affective representations in the orbitofrontal cortex, providing a mechanism for cognition to influence emotion. Whereas the orbitofrontal cortex provides a representation of reward or affective value on a continuous scale, areas beyond the orbitofrontal cortex such as the medial prefrontal cortex area 10 are involved in binary decision-making when a choice must be made. For this decision-making, the orbitofrontal cortex provides a representation of the value of each specific reward on the same scale, with no conversion to a common currency. Increased activity in a lateral orbitofrontal cortex non-reward area provides a new attractor-related approach to understanding and treating depression. Consistent with the theory, the lateral orbitofrontal cortex has increased functional connectivity in depression, and the medial orbitofrontal cortex, involved in reward, has decreased functional connectivity in

  19. Development of adrenal cortex zonation.

    PubMed

    Xing, Yewei; Lerario, Antonio M; Rainey, William; Hammer, Gary D

    2015-06-01

    The human adult adrenal cortex is composed of the zona glomerulosa (zG), zona fasciculata (zF), and zona reticularis (zR), which are responsible for production of mineralocorticoids, glucocorticoids, and adrenal androgens, respectively. The final completion of cortical zonation in humans does not occur until puberty with the establishment of the zR and its production of adrenal androgens; a process called adrenarche. The maintenance of the adrenal cortex involves the centripetal displacement and differentiation of peripheral Sonic hedgehog-positive progenitors cells into zG cells that later transition to zF cells and subsequently zR cells.

  20. Neuroprotective and antiamnesic effects of Semax during experimental ischemic infarction of the cerebral cortex.

    PubMed

    Romanova, G A; Silachev, D N; Shakova, F M; Kvashennikova, Yu N; Viktorov, I V; Shram, S I; Myasoedov, N F

    2006-12-01

    Semax had a pronounced neuroprotective and antiamnesic effect during focal photoinduced ischemia of the prefrontal cortex. Intranasal administration of Semax for 6 days decreased the volume of cortical infarction and improved retention and performance of conditioned passive avoidance response.

  1. Stimulus contrast modulates functional connectivity in visual cortex

    PubMed Central

    Nauhaus, Ian; Busse, Laura; Carandini, Matteo; Ringach, Dario L

    2008-01-01

    Neurons in visual cortex are linked by an extensive network of lateral connections. To study the effect of these connections on neural responses, we recorded spikes and local field potentials (LFPs) from multi-electrode arrays that were implanted in monkey and cat primary visual cortex. Spikes at each location generated outward traveling LFP waves. When the visual stimulus was absent or had low contrast, these LFP waves had large amplitudes and traveled over long distances. Their effect was strong: LFP traces at any site could be predicted by the superposition of waves that were evoked by spiking in a ∼1.5-mm radius. As stimulus contrast increased, both the magnitude and the distance traveled by the waves progressively decreased. We conclude that the relative weight of feedforward and lateral inputs in visual cortex is not fixed, but rather depends on stimulus contrast. Lateral connections dominate at low contrast, when spatial integration of signals is perhaps most beneficial. PMID:19029885

  2. Spatial clustering of tuning in mouse primary visual cortex

    PubMed Central

    Ringach, Dario L.; Mineault, Patrick J.; Tring, Elaine; Olivas, Nicholas D.; Garcia-Junco-Clemente, Pablo; Trachtenberg, Joshua T.

    2016-01-01

    The primary visual cortex of higher mammals is organized into two-dimensional maps, where the preference of cells for stimulus parameters is arranged regularly on the cortical surface. In contrast, the preference of neurons in the rodent appears to be arranged randomly, in what is termed a salt-and-pepper map. Here we revisited the spatial organization of receptive fields in mouse primary visual cortex by measuring the tuning of pyramidal neurons in the joint orientation and spatial frequency domain. We found that the similarity of tuning decreases as a function of cortical distance, revealing a weak but statistically significant spatial clustering. Clustering was also observed across different cortical depths, consistent with a columnar organization. Thus, the mouse visual cortex is not strictly a salt-and-pepper map. At least on a local scale, it resembles a degraded version of the organization seen in higher mammals, hinting at a possible common origin. PMID:27481398

  3. Infralimbic cortex activation and motivated arousal induce histamine release.

    PubMed

    Riveros, María Eugenia; Forray, María Inés; Torrealba, Fernando

    2015-06-01

    Appetitive behaviours occur in a state of behavioural and physiological activation that allows the optimal performance of these goal-directed behaviours. Here, we tested the hypothesis that histamine neurons under the command of the infralimbic cortex are important to provide behavioural activation. Extracellular histamine and serotonin were measured by microdialysis of the medial prefrontal cortex in behaving rats in parallel with a picrotoxin microinjection into the infralimbic cortex. The injection aroused the rats behaviourally, increased histamine release and decreased serotonin levels. Inhibition of the infralimbic cortex with muscimol produced the opposite effects on neurotransmitter release. The behavioural activation induced by motivating hungry rats with caged food was paralleled by an immediate histamine release, whereas awakening induced by tapping their microdialysis bowl increased serotonin, but not histamine levels. In conclusion, picrotoxin injection into the infralimbic cortex produces behavioural activation together with histamine release; in a similar manner, induction of an appetitive state produced histamine release, likely related to increased behavioural activation characteristic of an appetitive behaviour.

  4. Trains of transcranial direct current stimulation antagonize motor cortex hypoexcitability induced by acute hemicerebellectomy.

    PubMed

    Ben Taib, Nordeyn Oulad; Manto, Mario

    2009-10-01

    The cerebellum is a key modulator of motor cortex activity, allowing both the maintenance and fine-tuning of motor cortex discharges. One elemental defect associated with acute cerebellar lesions is decreased excitability of the contralateral motor cortex, which is assumed to participate in deficits in skilled movements and considered a major defect in motor cortex properties. In the present study, the authors assessed the effect of trains of anodal transcranial direct current stimulation (tDCS), which elicits polarity-dependent shifts in resting membrane potentials. Transcranial DCS countered the defect in motor cortex excitability contralaterally to the hemicerebellar ablation. The depression of both the H-reflex and F wave remained unchanged with tDCS, and cutaneomuscular reflexes remained unaffected. Transcranial DCS antagonized motor cortex hypoexcitability induced by high-frequency stimulation of interpositus nucleus. The authors' results show that tDCS has the potential to modulate motor cortex excitability after acute cerebellar dysfunction. By putting the motor cortex at the appropriate level of excitability, tDCS might allow the motor cortex to become more reactive to the procedures of training or learning.

  5. Chronic Stress Alters Neural Activity in Medial Prefrontal Cortex During Retrieval of Extinction

    PubMed Central

    Wilber, Aaron A.; Walker, Adam G.; Southwood, Christopher J.; Farrell, Mollee R.; Lin, Grant L.; Rebec, George V.; Wellman, Cara L.

    2010-01-01

    Chronic restraint stress produces morphological changes in medial prefrontal cortex and disrupts a prefrontally mediated behavior, retrieval of extinction. To assess potential physiological correlates of these alterations, we compared neural activity in infralimbic and prelimbic cortex of unstressed versus stressed rats during fear conditioning and extinction. After implantation of microwire bundles into infralimbic or prelimbic cortex, rats were either unstressed or stressed via placement in a plastic restrainer (3 h/day for 1 week). Rats then underwent fear conditioning and extinction while activity of neurons in infralimbic or prelimbic cortex was recorded. Percent freezing and neural activity were assessed during all phases of training. Chronic stress enhanced freezing during acquisition of conditioned fear, and altered both prelimbic and infralimbic activity during this phase. Stress did not alter initial extinction or conditioned stimulus (CS)-related activity during this phase. However, stress impaired retrieval of extinction assessed 24 h later, and this was accompanied by alterations in neuronal activity in both prelimbic and infralimbic cortex. In prelimbic cortex, unstressed rats showed decreased activity in response to CS presentation, whereas stressed rats showed no change. In infralimbic cortex, neurons in unstressed rats exhibited increased firing in response to the CS, whereas stressed rats showed no increase in infralimbic firing during the tone. Finally, CS-related firing in infralimbic but not prelimbic cortex was correlated with extinction retrieval. Thus, the stress-induced alteration of neuronal activity in infralimbic cortex may be responsible for the stress-induced deficit in retrieval of extinction. PMID:21044660

  6. Population coding in somatosensory cortex.

    PubMed

    Petersen, Rasmus S; Panzeri, Stefano; Diamond, Mathew E

    2002-08-01

    Computational analyses have begun to elucidate which components of somatosensory cortical population activity may encode basic stimulus features. Recent results from rat barrel cortex suggest that the essence of this code is not synergistic spike patterns, but rather the precise timing of single neuron's first post-stimulus spikes. This may form the basis for a fast, robust population code.

  7. Effect of arginine vasopressin on the cortex edema in the ischemic stroke of Mongolian gerbils.

    PubMed

    Zhao, Xue-Yan; Wu, Chun-Fang; Yang, Jun; Gao, Yang; Sun, Fang-Jie; Wang, Da-Xin; Wang, Chang-Hong; Lin, Bao-Cheng

    2015-06-01

    Brain edema formation is one of the most important mechanisms of ischemia-evoked cerebral edema. It has been demonstrated that arginine vasopressin (AVP) receptors are involved in the pathophysiology of secondary brain damage after focal cerebral ischemia. In a well-characterized animal model of ischemic stroke of Mongolian gerbils, the present study was undertaken to clear the effect of AVP on cortex edema in cerebral ischemia. The results showed that (1) occluding the left carotid artery of Mongolian gerbils not only decreased the cortex specific gravity (cortex edema) but also increased AVP levels in the ipsilateral cortex (ischemic area) including left prefrontal lobe, left parietal lobe, left temporal lobe, left occipital lobe and left hippocampus for the first 6 hours, and did not change of the cortex specific gravity and AVP concentration in the right cortex (non-ischemic area); (2) there were many negative relationships between the specific gravity and AVP levels in the ischemic cortex; (3) intranasal AVP (50 ng or 200 ng), which could pass through the blood-brain barrier to the brain, aggravated the focal cortex edema, whereas intranasal AVP receptor antagonist-D(CH2)5Tyr(ET)DAVP (2 µg) mitigated the cortex edema in the ischemic area after occluding the left carotid artery of Mongolian gerbils; and (4) either intranasal AVP or AVP receptor antagonist did not evoke that edema in the non-ischemic cortex. The data indicated that AVP participated in the process of ischemia-evoked cortex edema, and the cerebral AVP receptor might serve as an important therapeutic target for the ischemia-evoked cortex edema.

  8. Functions of the orbitofrontal and pregenual cingulate cortex in taste, olfaction, appetite and emotion.

    PubMed

    Rolls, E T

    2008-06-01

    Complementary neurophysiological recordings in macaques and functional neuroimaging in humans show that the primary taste cortex in the rostral insula and adjoining frontal operculum provides separate and combined representations of the taste, temperature, and texture (including viscosity and fat texture) of food in the mouth independently of hunger and thus of reward value and pleasantness. One synapse on, in the orbitofrontal cortex, these sensory inputs are for some neurons combined by learning with olfactory and visual inputs. Different neurons respond to different combinations, providing a rich representation of the sensory properties of food. The representation of taste and other food-related stimuli in the orbitofrontal cortex of macaques is found from its lateral border throughout area 13 to within 7 mm of the midline, and in humans the representation of food-related and other pleasant stimuli is found particularly in the medial orbitofrontal cortex. In the orbitofrontal cortex, feeding to satiety with one food decreases the responses of these neurons to that food, but not to other foods, showing that sensory-specific satiety is computed in the primate (including human) orbitofrontal cortex. Consistently, activation of parts of the human orbitofrontal cortex correlates with subjective ratings of the pleasantness of the taste and smell of food. Cognitive factors, such as a word label presented with an odour, influence the pleasantness of the odour, and the activation produced by the odour in the orbitofrontal cortex. Food intake is thus controlled by building a multimodal representation of the sensory properties of food in the orbitofrontal cortex, and gating this representation by satiety signals to produce a representation of the pleasantness or reward value of food which drives food intake. A neuronal representation of taste is also found in the pregenual cingulate cortex, which receives inputs from the orbitofrontal cortex, and in humans many pleasant

  9. [Risk taking and the insular cortex].

    PubMed

    Ishii, Hironori; Tsutsui, Ken-Ichiro; Iijima, Toshio

    2013-08-01

    Risk taking can lead to ruin, but sometimes, it can also provide great success. How does our brain make a decision on whether to take a risk or to play it safe? Recent studies have revealed the neural basis of risky decision making. In this review, we focus on the role of the anterior insular cortex (AIC) in risky decision making. Although human imaging studies have shown activations of the AIC in various gambling tasks, the causal involvement of the AIC in risky decision making was still unclear. Recently, we demonstrated a causality of the AIC in risky decision making by using a pharmacological approach in behaving rats-temporary inactivation of the AIC decreased the risk preference in gambling tasks, whereas temporary inactivation of the adjacent orbitofrontal cortex (OFC) increased the risk preference. The latter finding is consistent with a previous finding that patients with damage to the OFC take abnormally risky decisions in the Iowa gambling task. On the basis of these observations, we hypothesize that the intact AIC promotes risk-seeking behavior, and that the AIC and OFC are crucial for balancing the opposing motives of whether to take a risk or avoid it. However, the functional relationship between the AIC and OFC remains unclear. Future combinations of inactivation and electrophysiological studies may promote further understanding of risky decision making.

  10. Extra-1 acupressure for children undergoing anesthesia.

    PubMed

    Wang, Shu-Ming; Escalera, Sandra; Lin, Eric C; Maranets, Inna; Kain, Zeev N

    2008-09-01

    Acupuncture and related techniques have been used as adjuncts for perioperative anesthesia management. We examined whether acupressure in the Extra-1 (Yin-Tang) point would result in decreased preprocedural anxiety and reduced intraprocedural propofol requirements in a group of children undergoing endoscopic procedures. Fifty-two children were randomized to receive acupressure bead intervention either at the Extra-1 acupuncture point or at a sham point. A Bispectral Index (BIS) monitor was applied to all children before the onset of the intervention. Anxiety was assessed at baseline and before entrance to the operating room. Anesthetic techniques were standardized and maintained with IV propofol infusion titrated to keep BIS values of 40-60. We found that after the intervention, children in the Extra-1 group experienced reduced anxiety whereas children in the sham group experienced increased anxiety (-9% [-3 to -15] vs 2% [-6 to 7.4], P = 0.012). In contrast, no significant changes in BIS values were observed in the preprocedural waiting period between groups (P = ns). We also found that total intraprocedural propofol requirements did not differ between the two study groups (214 +/- 76 microg x kg(-1) x min(-1) vs 229 +/- 95 microg x kg(-1) x min(-1), P = 0.52). We conclude that acupressure bead intervention at Extra-1 acupoint reduces preprocedural anxiety in children undergoing endoscopic procedures. This intervention, however, has no impact on BIS values or intraprocedural propofol requirements.

  11. Systemic or intra-prelimbic cortex infusion of prazosin impairs fear memory reconsolidation.

    PubMed

    Do Monte, Fabricio H; Souza, Rimenez R; Wong, Ting T; Carobrez, Antonio de Padua

    2013-05-01

    The alpha-1 adrenergic antagonist prazosin has been used to alleviate the symptoms of PTSD, but the mechanism remains unclear. One possibility is that prazosin may disrupt fear memory reconsolidation, leading to attenuation of fear responses. To test this hypothesis, we administered a single systemic injection of prazosin during the reconsolidation of olfactory fear conditioning in rats. We found that a post-retrieval injection of prazosin disrupted subsequent retrieval of fear. Similarly, intra-prelimbic cortex infusion of prazosin during the reconsolidation period also disrupted subsequent retrieval of fear. These findings suggest that fear memory undergoes reconsolidation through activation of alpha-1 adrenergic receptors in the prelimbic cortex.

  12. Heterotopic autotransplantation of ovarian cortex in cynomolgus monkeys.

    PubMed

    Igarashi, Suguru; Suzuki, Nao; Hashimoto, Shu; Takae, Seido; Takenoshita, Makoto; Hosoi, Yoshihiko; Morimoto, Yoshiharu; Ishizuka, Bunpei

    2010-02-01

    Abstract In recent years, removal of ova or ovaries before chemotherapy or radiation therapy has been investigated in young female cancer patients to avoid the adverse effects of treatment. Orthotopic autotransplantation of ovarian cortex has advantages such as easy collection of ova and the possibility of spontaneous pregnancy. Although children have been born after successful orthotopic autotransplantation into the residual ovaries, some patients cannot undergo this procedure such as those who need bilateral ovariectomy or pelvic radiation therapy, therefore it is still necessary to investigate suitable heterotopic autotransplantation sites. The present study was performed in primates (cynomolgus monkeys) with the objective of determining the optimum site for heterotopic autotransplantation of ovarian cortex to enhance the clinical application of this method. The retroperitoneal iliac fossa and omentum were selected as sites for heterotopic autotransplantation. Two cynomolgus monkeys were subjected to laparotomy under anesthesia. After resection of the bilateral adnexae, the ovaries were cut into 0.5 cm cubes that were transplanted. Blood levels of follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone were monitored, and monkeys with a regular estrus cycle underwent superovulation and egg collection. In both monkeys studied, recovery of a regular estrus cycle was confirmed after heterotopic autotransplantation of ovarian tissue. MII phase ova were successfully collected from tissues transplanted into the retroperitoneal iliac fossa or omentum. Development to the early blastocyst stage was confirmed after microfertilization. We established an appropriate method of heterotopic autotransplantation using ovarian cortex into the retroperitoneal iliac fossa or omentum in primates.

  13. The rat cortex in stereotaxic coordinates.

    PubMed

    Schober, W

    1986-01-01

    On the basis of Nissl-preparations the cortex of albino rats has been mapped cytoarchitectonically. 13 frontal sections through the cortex are illustrated with coordinates. Therewith exists a stereotaxic atlas of the cortex of the rat and one can realize exactly experimental investigations in the different cortical areas.

  14. The Functions of the Orbitofrontal Cortex

    ERIC Educational Resources Information Center

    Rolls, Edmund T.

    2004-01-01

    The orbitofrontal cortex contains the secondary taste cortex, in which the reward value of taste is represented. It also contains the secondary and tertiary olfactory cortical areas, in which information about the identity and also about the reward value of odours is represented. The orbitofrontal cortex also receives information about the sight…

  15. The Functions of the Orbitofrontal Cortex

    ERIC Educational Resources Information Center

    Rolls, Edmund T.

    2004-01-01

    The orbitofrontal cortex contains the secondary taste cortex, in which the reward value of taste is represented. It also contains the secondary and tertiary olfactory cortical areas, in which information about the identity and also about the reward value of odours is represented. The orbitofrontal cortex also receives information about the sight…

  16. Schur monotone decreasing sequences

    NASA Astrophysics Data System (ADS)

    Ganikhodjaev, Rasul; Saburov, Mansoor; Saburov, Khikmat

    2013-09-01

    In this paper, we introduce Schur monotone decreasing sequences in an n-dimensional space by considering a majorization pre-order. By means of down arrow mappings, we study omega limiting points of bounded Schur monotone decreasing sequences. We provide convergence criteria for such kinds of sequences. We prove that a Cesaro mean (or an arithmetic mean) of any bounded Schur monotone decreasing sequences converges to a unique limiting point.

  17. Extended access to cocaine self-administration produces long-lasting prefrontal cortex-dependent working memory impairments.

    PubMed

    George, Olivier; Mandyam, Chitra D; Wee, Sunmee; Koob, George F

    2008-09-01

    Humans with drug addiction exhibit compulsive drug-seeking associated with impairment of prefrontal cortex cognitive function. Whether prefrontal cortex dysfunction is a consequence of chronic drug exposure, or mediates the transition from drug use to drug dependence, is unknown. The current study investigates whether a history of escalated vs controlled cocaine intake is associated with specific working memory impairments, and long-lasting alterations of the dorsomedial prefrontal cortex and orbitofrontal cortex in rats. Working memory was assessed in rats with a history of extended (6 h per session) or limited (1 h per session) access to cocaine (0.5 mg/kg per injection), 3-17 days after the last self-administration session, using a delayed nonmatching-to-sample task. The density of neurons, oligodendrocytes, and astrocytes was quantified in the dorsomedial prefrontal cortex and orbitofrontal prefrontal cortex 2 months after the last self-administration session. Working memory impairments were observed after a history of chronic and escalated cocaine intake, but not after repeated limited access to cocaine. Moreover, working memory impairments were correlated with a decreased density of neurons and oligodendrocytes but not astrocytes in the dorsomedial prefrontal cortex, and with a decreased density of oligodendrocytes in the orbitofrontal cortex. Considering the role of the prefrontal cortex in goal-directed behavior, the prefrontal cortex dysfunctions observed here may exacerbate the loss of control associated with increased drug use and facilitate the progression to drug addiction.

  18. Differential grey matter changes in sensorimotor cortex related to exceptional fine motor skills.

    PubMed

    Stoeckel, M Cornelia; Morgenroth, Farina; Buetefisch, Cathrin M; Seitz, Rüdiger J

    2012-01-01

    Functional changes in sensorimotor representation occur in response to use and lesion throughout life. Emerging evidence suggests that functional changes are paralleled by respective macroscopic structural changes. In the present study we used voxel-based morphometry to investigate sensorimotor cortex in subjects with congenitally malformed upper extremities. We expected increased or decreased grey matter to parallel the enlarged or reduced functional representations we reported previously. More specifically, we expected decreased grey matter values in lateral sensorimotor cortex related to compromised hand function and increased grey matter values in medial sensorimotor cortex due to compensatory foot use. We found a medial cluster of grey matter increase in subjects with frequent, hand-like compensatory foot use. This increase was predominantly seen for lateral premotor, supplementary motor, and motor areas and only marginally involved somatosensory cortex. Contrary to our expectation, subjects with a reduced number of fingers, who had shown shrinkage of the functional hand representation previously, did not show decreased grey matter values within lateral sensorimotor cortex. Our data suggest that functional plastic changes in sensorimotor cortex can be associated with increases in grey matter but may also occur in otherwise macroscopically normal appearing grey matter volumes. Furthermore, macroscopic structural changes in motor and premotor areas may be observed without respective changes in somatosensory cortex.

  19. Periodontal tactile input activates the prefrontal cortex

    PubMed Central

    Higaki, Nobuaki; Goto, Takaharu; Ichikawa, Tetsuo

    2016-01-01

    The prefrontal cortex (PFC) plays a role in complex cognitive behavioural planning, decision-making, and social behaviours. However, the effects of sensory integration during motor tasks on PFC activation have not been studied to date. Therefore, we investigated the effect of peripheral sensory information and external information on PFC activation using functional near-infrared spectroscopy (fNIRS). Cerebral blood flow (CBF) was increased around bilateral Brodmann areas 46 and 10 during visual and auditory information integration during an occlusal force (biting) task. After local anesthesia, CBF values were significantly decreased, but occlusal force was similar. In conclusion, the effects of peripheral sensory information from the periodontal ligament and external information have minimal impacts on occlusal force maintenance but are important for PFC activation. PMID:27833164

  20. Perimovement decrease of alpha/beta oscillations in the human nucleus accumbens

    PubMed Central

    Dürschmid, Stefan; Rutledge, Robb B.; Zaehle, Tino; Schmitt, Friedhelm C.; Kaufmann, Jörn; Voges, Jürgen; Heinze, Hans-Jochen; Dolan, Raymond J.; Schoenfeld, Mircea Ariel

    2016-01-01

    The human nucleus accumbens is thought to play an important role in guiding future action selection via an evaluation of current action outcomes. Here we provide electrophysiological evidence for a more direct, i.e., online, role during action preparation. We recorded local field potentials from the nucleus accumbens in patients with epilepsy undergoing surgery for deep brain stimulation. We found a consistent decrease in the power of alpha/beta oscillations (10–30 Hz) before and around the time of movements. This perimovement alpha/beta desynchronization was observed in seven of eight patients and was present both before instructed movements in a serial reaction time task as well as before self-paced, deliberate choices in a decision making task. A similar beta decrease over sensorimotor cortex and in the subthalamic nucleus has been directly related to movement preparation and execution. Our results support the idea of a direct role of the human nucleus accumbens in action preparation and execution. PMID:27486103

  1. Encoding of sound envelope transients in the auditory cortex of juvenile rats and adult rats.

    PubMed

    Lu, Qi; Jiang, Cuiping; Zhang, Jiping

    2016-02-01

    Accurate neural processing of time-varying sound amplitude and spectral information is vital for species-specific communication. During postnatal development, cortical processing of sound frequency undergoes progressive refinement; however, it is not clear whether cortical processing of sound envelope transients also undergoes age-related changes. We determined the dependence of neural response strength and first-spike latency on sound rise-fall time across sound levels in the primary auditory cortex (A1) of juvenile (P20-P30) rats and adult (8-10 weeks) rats. A1 neurons were categorized as "all-pass", "short-pass", or "mixed" ("all-pass" at high sound levels to "short-pass" at lower sound levels) based on the normalized response strength vs. rise-fall time functions across sound levels. The proportions of A1 neurons within each of the three categories in juvenile rats were similar to that in adult rats. In general, with increasing rise-fall time, the average response strength decreased and the average first-spike latency increased in A1 neurons of both groups. At a given sound level and rise-fall time, the average normalized neural response strength did not differ significantly between the two age groups. However, the A1 neurons in juvenile rats showed greater absolute response strength, longer first-spike latency compared to those in adult rats. In addition, at a constant sound level, the average first-spike latency of juvenile A1 neurons was more sensitive to changes in rise-fall time. Our results demonstrate the dependence of the responses of rat A1 neurons on sound rise-fall time, and suggest that the response latency exhibit some age-related changes in cortical representation of sound envelope rise time.

  2. 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

  3. Brain glycogen decreases during prolonged exercise

    PubMed Central

    Matsui, Takashi; Soya, Shingo; Okamoto, Masahiro; Ichitani, Yukio; Kawanaka, Kentaro; Soya, Hideaki

    2011-01-01

    Abstract Brain glycogen could be a critical energy source for brain activity when the glucose supply from the blood is inadequate (hypoglycaemia). Although untested, it is hypothesized that during prolonged exhaustive exercise that induces hypoglycaemia and muscular glycogen depletion, the resultant hypoglycaemia may cause a decrease in brain glycogen. Here, we tested this hypothesis and also investigated the possible involvement of brain monoamines with the reduced levels of brain glycogen. For this purpose, we exercised male Wistar rats on a treadmill for different durations (30–120 min) at moderate intensity (20 m min−1) and measured their brain glycogen levels using high-power microwave irradiation (10 kW). At the end of 30 and 60 min of running, the brain glycogen levels remained unchanged from resting levels, but liver and muscle glycogen decreased. After 120 min of running, the glycogen levels decreased significantly by ∼37–60% in five discrete brain loci (the cerebellum 60%, cortex 48%, hippocampus 43%, brainstem 37% and hypothalamus 34%) compared to those of the sedentary control. The brain glycogen levels in all five regions after running were positively correlated with the respective blood and brain glucose levels. Further, in the cortex, the levels of methoxyhydroxyphenylglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA), potential involved in degradation of the brain glycogen, increased during prolonged exercise and negatively correlated with the glycogen levels. These results support the hypothesis that brain glycogen could decrease with prolonged exhaustive exercise. Increased monoamines together with hypoglycaemia should be associated with the development of decreased brain glycogen, suggesting a new clue towards the understanding of central fatigue during prolonged exercise. PMID:21521757

  4. ALCOHOL AND THE PREFRONTAL CORTEX

    PubMed Central

    Abernathy, Kenneth; Chandler, L. Judson; Woodward, John J.

    2013-01-01

    The prefrontal cortex occupies the anterior portion of the frontal lobes and is thought to be one of the most complex anatomical and functional structures of the mammalian brain. Its major role is to integrate and interpret inputs from cortical and sub-cortical structures and use this information to develop purposeful responses that reflect both present and future circumstances. This includes both action-oriented sequences involved in obtaining rewards and inhibition of behaviors that pose undue risk or harm to the individual. Given the central role in initiating and regulating these often complex cognitive and behavioral responses, it is no surprise that alcohol has profound effects on the function of the prefrontal cortex. In this chapter, we review the basic anatomy and physiology of the prefrontal cortex and discuss what is known about the actions of alcohol on the function of this brain region. This includes a review of both the human and animal literature including information on the electrophysiological and behavioral effects that follow acute and chronic exposure to alcohol. The chapter concludes with a discussion of unanswered questions and areas needing further investigation. PMID:20813246

  5. Stratospheric ozone is decreasing

    NASA Astrophysics Data System (ADS)

    Kerr, Richard A.

    1988-03-01

    The recent discovery that chlorofluorocarbons create the Antarctic ozone hole every October through reactions mediated by ice particles formed at the lowest temperatures of the stratosphere is discussed. A large-scale reanalysis of measurements reveals that protective stratospheric ozone has decreased during the past 17 yrs with some decreases greatly exceeding predictions. It is noted that standard models did not, and still do not, include the ice in their reaction schemes. A tendency toward larger losses at higher colder latitudes is seen.

  6. Heterogeneous neuronal firing patterns during interictal epileptiform discharges in the human cortex.

    PubMed

    Keller, Corey J; Truccolo, Wilson; Gale, John T; Eskandar, Emad; Thesen, Thomas; Carlson, Chad; Devinsky, Orrin; Kuzniecky, Ruben; Doyle, Werner K; Madsen, Joseph R; Schomer, Donald L; Mehta, Ashesh D; Brown, Emery N; Hochberg, Leigh R; Ulbert, István; Halgren, Eric; Cash, Sydney S

    2010-06-01

    Epileptic cortex is characterized by paroxysmal electrical discharges. Analysis of these interictal discharges typically manifests as spike-wave complexes on electroencephalography, and plays a critical role in diagnosing and treating epilepsy. Despite their fundamental importance, little is known about the neurophysiological mechanisms generating these events in human focal epilepsy. Using three different systems of microelectrodes, we recorded local field potentials and single-unit action potentials during interictal discharges in patients with medically intractable focal epilepsy undergoing diagnostic workup for localization of seizure foci. We studied 336 single units in 20 patients. Ten different cortical areas and the hippocampus, including regions both inside and outside the seizure focus, were sampled. In three of these patients, high density microelectrode arrays simultaneously recorded between 43 and 166 single units from a small (4 mm x 4 mm) patch of cortex. We examined how the firing rates of individual neurons changed during interictal discharges by determining whether the firing rate during the event was the same, above or below a median baseline firing rate estimated from interictal discharge-free periods (Kruskal-Wallis one-way analysis, P<0.05). Only 48% of the recorded units showed such a modulation in firing rate within 500 ms of the discharge. Units modulated during the discharge exhibited significantly higher baseline firing and bursting rates than unmodulated units. As expected, many units (27% of the modulated population) showed an increase in firing rate during the fast segment of the discharge (+ or - 35 ms from the peak of the discharge), while 50% showed a decrease during the slow wave. Notably, in direct contrast to predictions based on models of a pure paroxysmal depolarizing shift, 7.7% of modulated units recorded in or near the seizure focus showed a decrease in activity well ahead (0-300 ms) of the discharge onset, while 12.2% of

  7. Heterogeneous neuronal firing patterns during interictal epileptiform discharges in the human cortex

    PubMed Central

    Keller, Corey J.; Truccolo, Wilson; Gale, John T.; Eskandar, Emad; Thesen, Thomas; Carlson, Chad; Devinsky, Orrin; Kuzniecky, Ruben; Doyle, Werner K.; Madsen, Joseph R.; Schomer, Donald L.; Mehta, Ashesh D.; Brown, Emery N.; Hochberg, Leigh R.; Ulbert, István; Halgren, Eric

    2010-01-01

    Epileptic cortex is characterized by paroxysmal electrical discharges. Analysis of these interictal discharges typically manifests as spike–wave complexes on electroencephalography, and plays a critical role in diagnosing and treating epilepsy. Despite their fundamental importance, little is known about the neurophysiological mechanisms generating these events in human focal epilepsy. Using three different systems of microelectrodes, we recorded local field potentials and single-unit action potentials during interictal discharges in patients with medically intractable focal epilepsy undergoing diagnostic workup for localization of seizure foci. We studied 336 single units in 20 patients. Ten different cortical areas and the hippocampus, including regions both inside and outside the seizure focus, were sampled. In three of these patients, high density microelectrode arrays simultaneously recorded between 43 and 166 single units from a small (4 mm × 4 mm) patch of cortex. We examined how the firing rates of individual neurons changed during interictal discharges by determining whether the firing rate during the event was the same, above or below a median baseline firing rate estimated from interictal discharge-free periods (Kruskal–Wallis one-way analysis, P<0.05). Only 48% of the recorded units showed such a modulation in firing rate within 500 ms of the discharge. Units modulated during the discharge exhibited significantly higher baseline firing and bursting rates than unmodulated units. As expected, many units (27% of the modulated population) showed an increase in firing rate during the fast segment of the discharge (±35 ms from the peak of the discharge), while 50% showed a decrease during the slow wave. Notably, in direct contrast to predictions based on models of a pure paroxysmal depolarizing shift, 7.7% of modulated units recorded in or near the seizure focus showed a decrease in activity well ahead (0–300 ms) of the discharge onset, while 12.2% of

  8. Altered GABAergic markers, increased binocularity and reduced plasticity in the visual cortex of Engrailed-2 knockout mice

    PubMed Central

    Allegra, Manuela; Genovesi, Sacha; Maggia, Marika; Cenni, Maria C.; Zunino, Giulia; Sgadò, Paola; Caleo, Matteo; Bozzi, Yuri

    2014-01-01

    The maturation of the GABAergic system is a crucial determinant of cortical development during early postnatal life, when sensory circuits undergo a process of activity-dependent refinement. An altered excitatory/inhibitory balance has been proposed as a possible pathogenic mechanism of autism spectrum disorders (ASD). The homeobox-containing transcription factor Engrailed-2 (En2) has been associated to ASD, and En2 knockout (En2−/−) mice show ASD-like features accompanied by a partial loss of cortical GABAergic interneurons. Here we studied GABAergic markers and cortical function in En2−/− mice, by exploiting the well-known anatomical and functional features of the mouse visual system. En2 is expressed in the visual cortex at postnatal day 30 and during adulthood. When compared to age-matched En2+/+ controls, En2−/− mice showed an increased number of parvalbumin (PV+), somatostatin (SOM+), and neuropeptide Y (NPY+) positive interneurons in the visual cortex at P30, and a decreased number of SOM+ and NPY+ interneurons in the adult. At both ages, the differences in distinct interneuron populations observed between En2+/+ and En2−/− mice were layer-specific. Adult En2−/− mice displayed a normal eye-specific segregation in the retino-geniculate pathway, and in vivo electrophysiological recordings showed a normal development of basic functional properties (acuity, response latency, receptive field size) of the En2−/− primary visual cortex. However, a significant increase of binocularity was found in P30 and adult En2−/− mice, as compared to age-matched controls. Differently from what observed in En2+/+ mice, the En2−/− primary visual cortex did not respond to a brief monocular deprivation performed between P26 and P29, during the so-called “critical period.” These data suggest that altered GABAergic circuits impact baseline binocularity and plasticity in En2−/− mice, while leaving other visual functional properties unaffected

  9. PKA inhibits WNT signalling in adrenal cortex zonation and prevents malignant tumour development

    PubMed Central

    Drelon, Coralie; Berthon, Annabel; Sahut-Barnola, Isabelle; Mathieu, Mickaël; Dumontet, Typhanie; Rodriguez, Stéphanie; Batisse-Lignier, Marie; Tabbal, Houda; Tauveron, Igor; Lefrançois-Martinez, Anne-Marie; Pointud, Jean-Christophe; Gomez-Sanchez, Celso E.; Vainio, Seppo; Shan, Jingdong; Sacco, Sonia; Schedl, Andreas; Stratakis, Constantine A.; Martinez, Antoine; Val, Pierre

    2016-01-01

    Adrenal cortex physiology relies on functional zonation, essential for production of aldosterone by outer zona glomerulosa (ZG) and glucocorticoids by inner zona fasciculata (ZF). The cortex undergoes constant cell renewal, involving recruitment of subcapsular progenitors to ZG fate and subsequent lineage conversion to ZF identity. Here we show that WNT4 is an important driver of WNT pathway activation and subsequent ZG differentiation and demonstrate that PKA activation prevents ZG differentiation through WNT4 repression and WNT pathway inhibition. This suggests that PKA activation in ZF is a key driver of WNT inhibition and lineage conversion. Furthermore, we provide evidence that constitutive PKA activation inhibits, whereas partial inactivation of PKA catalytic activity stimulates β-catenin-induced tumorigenesis. Together, both lower PKA activity and higher WNT pathway activity lead to poorer prognosis in adrenocortical carcinoma (ACC) patients. These observations suggest that PKA acts as a tumour suppressor in the adrenal cortex, through repression of WNT signalling. PMID:27624192

  10. [Nutritional status of patients undergoing peritoneal dialysis].

    PubMed

    Bober, Joanna; Mazur, Olech; Gołembiewska, Edyta; Bogacka, Anna; Sznabel, Karina; Stańkowska-Walczak, Dobrosława; Kabat-Koperska, Joanna; Stachowska, Ewa

    2015-01-01

    The main causes of death in patients undergoing dialysis are cardiovascular diseases. Their presence is related to the nutritional status of patients treated with peritoneal dialysis, and has a predicted value in this kind of patient. Long-term therapy entails unfavourable changes, from which a clinically significant complication is protein-energy malnutrition and intensification of inflammatory processes. The aim of the study was to assess the nutritional status of patients with chronic kidney disease treated with peritoneal dialysis based on anthropometric, biochemical parameters analysis, a survey, as well as the determination of changes in measured parameters occurring over time. The study involved 40 people undergoing peritoneal dialysis (PD) and 30 healthy people. For dialyzed patients testing material was collected twice, every 6 months. Proteins, albumins, prealbumins, C-reactive protein and glucose levels were measured. Anthropometric measurements included body height, body weight, triceps skinfold and subscapular skinfold thickness. Body mass index (BMI) value and exponent of tissue protein source were calculated. The examined patients completed the questionnaire, which included, among other factors, the daily intake of nutrients, and lifestyle information. During the 6 month observation of the PD group a stastically significant increase in the energy value of intake food and amount of calories intake from carbohydrates was found. Analysis of nutritional status dependent on the BMI showed that overweight and obese patients are characterized by higher concentrations of the C-reactive protein and glucose, as well as lower concentrations of prealbumin compared to patients with normal body weight. At the same time, the energy value of food and the amount of protein in the group with BMI > 25 were smaller than in the other groups. During the 6 month observation a decrease the concentration of prealbumin and an increase in C-reactive protein in BMI > 25 group

  11. Decreasing strabismus surgery

    PubMed Central

    Arora, A; Williams, B; Arora, A K; McNamara, R; Yates, J; Fielder, A

    2005-01-01

    Aim: To determine whether there has been a consistent change across countries and healthcare systems in the frequency of strabismus surgery in children over the past decade. Methods: Retrospective analysis of data on all strabismus surgery performed in NHS hospitals in England and Wales, on children aged 0–16 years between 1989 and 2000, and between 1994 and 2000 in Ontario (Canada) hospitals. These were compared with published data for Scotland, 1989–2000. Results: Between 1989 and 1999–2000 the number of strabismus procedures performed on children, 0–16 years, in England decreased by 41.2% from 15 083 to 8869. Combined medial rectus recession with lateral rectus resection decreased from 5538 to 3013 (45.6%) in the same period. Bimedial recessions increased from 489 to 762, oblique tenotomies from 43 to 121, and the use of adjustable sutures from 29 to 44, in 2000. In Ontario, operations for squint decreased from 2280 to 1685 (26.1%) among 0–16 year olds between 1994 and 2000. Conclusion: The clinical impression of decrease in the frequency of paediatric strabismus surgery is confirmed. In the authors’ opinion this cannot be fully explained by a decrease in births or by the method of healthcare funding. Two factors that might have contributed are better conservative strabismus management and increased subspecialisation that has improved the quality of surgery and the need for re-operation. This finding has a significant impact upon surgical services and also on the training of ophthalmologists. PMID:15774914

  12. The Cortical Signature of Central Poststroke Pain: Gray Matter Decreases in Somatosensory, Insular, and Prefrontal Cortices.

    PubMed

    Krause, T; Asseyer, S; Taskin, B; Flöel, A; Witte, A V; Mueller, K; Fiebach, J B; Villringer, K; Villringer, A; Jungehulsing, G J

    2016-01-01

    It has been proposed that cortical structural plasticity plays a crucial role in the emergence and maintenance of chronic pain. Various distinct pain syndromes have accordingly been linked to specific patterns of decreases in regional gray matter volume (GMV). However, it is not known whether central poststroke pain (CPSP) is also associated with cortical structural plasticity. To determine this, we employed T1-weighted magnetic resonance imaging at 3 T and voxel-based morphometry in 45 patients suffering from chronic subcortical sensory stroke with (n = 23) and without CPSP (n = 22), and healthy matched controls (n = 31). CPSP patients showed decreases in GMV in comparison to healthy controls, involving secondary somatosensory cortex (S2), anterior as well as posterior insular cortex, ventrolateral prefrontal and orbitofrontal cortex, temporal cortex, and nucleus accumbens. Comparing CPSP patients to nonpain patients revealed a similar but more restricted pattern of atrophy comprising S2, ventrolateral prefrontal and temporal cortex. Additionally, GMV in the ventromedial prefrontal cortex negatively correlated to pain intensity ratings. This shows for the first time that CPSP is accompanied by a unique pattern of widespread structural plasticity, which involves the sensory-discriminative areas of insular/somatosensory cortex, but also expands into prefrontal cortex and ventral striatum, where emotional aspects of pain are processed.

  13. Cerebellar dentate nuclei lesions alter prefrontal cortex dendritic spine morphology.

    PubMed

    Bauer, David J; Peterson, Todd C; Swain, Rodney A

    2014-01-28

    Anatomical tracing studies in primates have revealed neural tracts from the cerebellar dentate nuclei to prefrontal cortex, implicating a cerebellar role in nonmotor processes. Experiments in rats examining the functional role of this cerebellothalamocortical pathway have demonstrated the development of visuospatial and motivational deficits following lesions of the dentate nuclei, in the absence of motor impairment. These behavioral deficits possibly occur due to structural modifications of the cerebral cortex secondary to loss of cerebellar input. The current study characterized morphological alterations in prefrontal cortex important for visuospatial and motivational processes following bilateral cerebellar dentate nuclei lesions. Rats received either bilateral electrolytic cerebellar dentate nuclei lesions or sham surgery followed by a 30-day recovery. Randomly selected Golgi-impregnated neurons in prefrontal cortex were examined for analysis. Measures of branch length and spine density revealed no differences between lesioned and sham rats in either apical or basilar arbors; however, the proportion of immature to mature spines significantly decreased in lesioned rats as compared to sham controls, with reductions of 33% in the basilar arbor and 28% in the apical arbor. Although expected pruning of branches and spines did not occur, the results are consistent with the hypothesis that cerebellar lesions influence prefrontal morphology and support the possibility that functional deficits following cerebellar dentate nuclei lesions are related to prefrontal morphological alteration.

  14. Human posterior auditory cortex gates novel sounds to consciousness.

    PubMed

    Jääskeläinen, Iiro P; Ahveninen, Jyrki; Bonmassar, Giorgio; Dale, Anders M; Ilmoniemi, Risto J; Levänen, Sari; Lin, Fa-Hsuan; May, Patrick; Melcher, Jennifer; Stufflebeam, Steven; Tiitinen, Hannu; Belliveau, John W

    2004-04-27

    Life or death in hostile environments depends crucially on one's ability to detect and gate novel sounds to awareness, such as that of a twig cracking under the paw of a stalking predator in a noisy jungle. Two distinct auditory cortex processes have been thought to underlie this phenomenon: (i) attenuation of the so-called N1 response with repeated stimulation and (ii) elicitation of a mismatch negativity response (MMN) by changes in repetitive aspects of auditory stimulation. This division has been based on previous studies suggesting that, unlike for the N1, repetitive "standard" stimuli preceding a physically different "novel" stimulus constitute a prerequisite to MMN elicitation, and that the source loci of MMN and N1 are different. Contradicting these findings, our combined electromagnetic, hemodynamic, and psychophysical data indicate that the MMN is generated as a result of differential adaptation of anterior and posterior auditory cortex N1 sources by preceding auditory stimulation. Early ( approximately 85 ms) neural activity within posterior auditory cortex is adapted as sound novelty decreases. This alters the center of gravity of electromagnetic N1 source activity, creating an illusory difference between N1 and MMN source loci when estimated by using equivalent current dipole fits. Further, our electroencephalography data show a robust MMN after a single standard event when the interval between two consecutive novel sounds is kept invariant. Our converging findings suggest that transient adaptation of feature-specific neurons within human posterior auditory cortex filters superfluous sounds from entering one's awareness.

  15. Auditory Evoked Bursts in Mouse Visual Cortex during Isoflurane Anesthesia

    PubMed Central

    Land, Rüdiger; Engler, Gerhard

    2012-01-01

    General anesthesia is not a uniform state of the brain. Ongoing activity differs between light and deep anesthesia and cortical response properties are modulated in dependence of anesthetic dosage. We investigated how anesthesia level affects cross-modal interactions in primary sensory cortex. To examine this, we continuously measured the effects of visual and auditory stimulation during increasing and decreasing isoflurane level in the mouse visual cortex and the subiculum (from baseline at 0.7 to 2.5 vol % and reverse). Auditory evoked burst activity occurred in visual cortex after a transition during increase of anesthesia level. At the same time, auditory and visual evoked bursts occurred in the subiculum, even though the subiculum was unresponsive to both stimuli previous to the transition. This altered sensory excitability was linked to the presence of burst suppression activity in cortex, and to a regular slow burst suppression rhythm (∼0.2 Hz) in the subiculum. The effect disappeared during return to light anesthesia. The results show that pseudo-heteromodal sensory burst responses can appear in brain structures as an effect of an anesthesia induced state change. PMID:23185462

  16. Locomotion in intact and in brain cortex-ablated cats.

    PubMed

    López Ruiz, José Roberto; Castillo Hernández, Luis; De la Torre Valdovinos, Braniff; Franco Rodríguez, Nancy Elizabeth; Dueñas Jiménez, Judith Marcela; Dueñas Jiménez, Alejandro; Rivas-Carrillo, Jorge David; Dueñas Jiménez, Sergio Horacio

    2017-09-01

    The current decerebration procedures discard the role of the thalamus in the motor control and decortication only rules out the brain cortex part, leaving a gap between the brain cortex and the subthalamic motor regions. In here we define a new preparation denominated Brain Cortex-Ablated Cat (BCAC), in which the frontal and parietal brain cortices as well as the central white matter beneath them were removed, this decerebration process may be considered as suprathalamic, since the thalamus remained intact. To characterize this preparation cat hindlimb electromyograms (EMG), kinematics and cutaneous reflexes (CR) produced by electrical stimulation of sural (SU) or saphenous (SAPH) nerves were analyzed during locomotion in intact and in BCAC. In cortex-ablated cats compared to intact cats, the hindlimb EMG amplitude was increased in the flexors, whereas in most extensors the amplitude was decreased. Bifunctional muscle EMGs presented complex and speed-dependent amplitude changes. In intact cats CR produced an inhibition of extensors, as well as excitation and inhibition of flexors, and a complex pattern of withdrawal responses in bifunctional muscles. The same stimuli applied to BCAC produced no detectable responses, but in some cats cutaneous reflexes produced by electrical stimulation of saphenous nerve reappeared when the locomotion speed increased. In BCAC, EMG and kinematic changes, as well as the absence of CR, imply that for this cat preparation there is a partial compensation due to the subcortical locomotor apparatus generating close to normal locomotion. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Parietal cortex and representation of the mental Self

    PubMed Central

    Lou, Hans C.; Luber, Bruce; Crupain, Michael; Keenan, Julian P.; Nowak, Markus; Kjaer, Troels W.; Sackeim, Harold A.; Lisanby, Sarah H.

    2004-01-01

    For a coherent and meaningful life, conscious self-representation is mandatory. Such explicit “autonoetic consciousness” is thought to emerge by retrieval of memory of personally experienced events (“episodic memory”). During episodic retrieval, functional imaging studies consistently show differential activity in medial prefrontal and medial parietal cortices. With positron-emission tomography, we here show that these medial regions are functionally connected and interact with lateral regions that are activated according to the degree of self-reference. During retrieval of previous judgments of Oneself, Best Friend, and the Danish Queen, activation increased in the left lateral temporal cortex and decreased in the right inferior parietal region with decreasing self-reference. Functionally, the former region was preferentially connected to medial prefrontal cortex, the latter to medial parietal. The medial parietal region may, then, be conceived of as a nodal structure in self-representation, functionally connected to both the right parietal and the medial prefrontal cortices. To determine whether medial parietal cortex in this network is essential for episodic memory retrieval with self-representation, we used transcranial magnetic stimulation over the region to transiently disturb neuronal circuitry. There was a decrease in the efficiency of retrieval of previous judgment of mental Self compared with retrieval of judgment of Other with transcranial magnetic stimulation at a latency of 160 ms, confirming the hypothesis. This network is strikingly similar to the network of the resting conscious state, suggesting that self-monitoring is a core function in resting consciousness. PMID:15096584

  18. Combat Casualties Undergoing Lifesaving Interventions Have Decreased Heart Rate Complexity at Multiple Time Scales

    DTIC Science & Technology

    2013-01-01

    almost half of the cases, related to delays in hemorrhage control during transportation or in resuscitation efforts. Earlier detection of hemorrhagic...restored to normal values with fluid resuscitation [311. On further analysis, we found that SampEn retained its ability to discriminate survivors from...information about HR dynamics in the neonatal ICU setting. They have developed a real time index, termed HR characteristics, which takes into

  19. Long-acting liposomal bupivacaine decreases inpatient narcotic requirements in men undergoing penile prosthesis implantation

    PubMed Central

    Cotta, Brittney H.; Welliver, Charles; Brahmamdam, Anand; Bednarchik, Cynthia L.; Dynda, Danuta; Köhler, Tobias S.

    2016-01-01

    Objective A new extended-release bupivacaine suspension bupivacaine (ERSB) delivers 3 days of local anesthetic and has been shown to reduce pain and narcotic usage in some patient groups but this issue is largely unstudied in urologic surgery. Material and methods We performed a single-surgeon retrospective chart review of the patients who underwent penile prosthesis implantation. Pain scores and standardized morphine equivalent (ME) dose data were collected during 23 hour- observation period. Subjects who received ERSB were compared with those who received standard bupivacaine or no local anesthesia. Results In a study population of 37 patients, those who received (n=13), and did not receive (n=24) ERSB were grouped, respectively. The groups were comparable demographically. ME was used 3.2 fold more frequently in the non-ERSB group (18.0, and 5.6 for non-ERSB, and ESRB groups, respectively (p=0.04). Mean overall pain scores were 3.8/10 for ERSB and 3.9/10 for non-ERSB group, respectively. Per patient medication cost for the control, and ERSB groups were $5.16 and $285.54, respectively. Conclusion The use of a new ERSB in penile prosthesis implants did lead to reduced narcotic consumption with comparable postoperative pain control to the non-ERSB group. However, the cost of the ERSB ($285/dose) may be prohibitive for its use. PMID:27909614

  20. Interactions between Pain and the Motor Cortex: Insights from Research on Phantom Limb Pain and Complex Regional Pain Syndrome

    PubMed Central

    Léonard, Guillaume

    2011-01-01

    ABSTRACT Purpose: Pain is a significantly disabling problem that often interacts with other deficits during the rehabilitation process. The aim of this paper is to review evidence of interactions between pain and the motor cortex in order to attempt to answer the following questions: (1) Does acute pain interfere with motor-cortex activity? (2) Does chronic pain interfere with motor-cortex activity, and, conversely, does motor-cortex plasticity contribute to chronic pain? (3) Can the induction of motor plasticity by means of motor-cortex stimulation decrease pain? (4) Can motor training result in both motor-cortex reorganization and pain relief? Summary of Key Points: Acute experimental pain has been clearly shown to exert an inhibitory influence over the motor cortex, which can interfere with motor learning capacities. Current evidence also suggests a relationship between chronic pain and motor-cortex reorganization, but it is still unclear whether one causes the other. However, there is growing evidence that interventions aimed at normalizing motor-cortex organization can lead to pain relief. Conclusions: Interactions between pain and the motor cortex are complex, and more studies are needed to understand these interactions in our patients, as well as to develop optimal rehabilitative strategies. PMID:22654236

  1. Gravitation and mass decrease

    SciTech Connect

    Schlegel, R.

    1982-08-01

    Consequences in physical theory of assuming the general relativistic time tranformation for the de Broglie frequencies of matter, v = E/h = mc/sup 2//h, are investigated in this paper. Experimentally it is known that electromagnetic waves from a source in a gravitational field are decreased in frequency, in accordance with the Einstein general relativity time transformation. An extension to de Broglie frequencies implies mass decreases in a gravitational field. Such a decrease gives an otherwise missing energy conservation for some processes; also, a physical alteration is then associated with change in gravitational potential. Further, the general relativity time transformation that is the source of gravitational action in the weak field (Newtonian) approximation than has a physical correlate in the proposed gravitational mass loss. Rotational motion and the associated equivalent gravitional-field mass loss are considered; an essential formal difference between metric (gravitational) mass loss and special relativity mass increase is discussed. For a spherical nonrotating mass collapsed to its Schwarzschild radius the postulated mass loss is found to give a 25% decrease in the mass acting as origin off an external gravitational field.

  2. Multimap formation in visual cortex

    PubMed Central

    Jain, Rishabh; Millin, Rachel; Mel, Bartlett W.

    2015-01-01

    An extrastriate visual area such as V2 or V4 contains neurons selective for a multitude of complex shapes, all sharing a common topographic organization. Simultaneously developing multiple interdigitated maps—hereafter a “multimap”—is challenging in that neurons must compete to generate a diversity of response types locally, while cooperating with their dispersed same-type neighbors to achieve uniform visual field coverage for their response type at all orientations, scales, etc. Previously proposed map development schemes have relied on smooth spatial interaction functions to establish both topography and columnar organization, but by locally homogenizing cells' response properties, local smoothing mechanisms effectively rule out multimap formation. We found in computer simulations that the key requirements for multimap development are that neurons are enabled for plasticity only within highly active regions of cortex designated “learning eligibility regions” (LERs), but within an LER, each cell's learning rate is determined only by its activity level with no dependence on location. We show that a hybrid developmental rule that combines spatial and activity-dependent learning criteria in this way successfully produces multimaps when the input stream contains multiple distinct feature types, or in the degenerate case of a single feature type, produces a V1-like map with “salt-and-pepper” structure. Our results support the hypothesis that cortical maps containing a fine mixture of different response types, whether in monkey extrastriate cortex, mouse V1 or elsewhere in the cortex, rather than signaling a breakdown of map formation mechanisms at the fine scale, are a product of a generic cortical developmental scheme designed to map cells with a diversity of response properties across a shared topographic space. PMID:26641946

  3. Intermittent Theta-Burst Stimulation of the Right Dorsolateral Prefrontal Cortex to Promote Metaphor Comprehension in Parkinson Disease: A Case Study.

    PubMed

    Tremblay, Christina; Monetta, Laura; Langlois, Mélanie; Schneider, Cyril

    2016-01-01

    This single-case research-designed study explored whether intermittent theta-burst stimulation (iTBS) of the right dorsolateral prefrontal cortex (DLPFC) could improve metaphor comprehension in people with Parkinson disease (PD) and language impairments. A right-handed participant with PD diagnosed 9 years ago, receiving long-term treatment with levodopa, and with metaphor comprehension impairment was recruited to undergo 10 sessions of sham stimulation (in 2wk), a washout period (6wk), and then 10 sessions of iTBS (in 2wk). Clinical scores of metaphor comprehension and motor evaluation (Unified Parkinson Disease Rating Scale part III) and transcranial magnetic stimulation to test the excitability of the primary motor cortex (M1) were used at baseline, postsham, post-iTBS, and at 3 follow-ups (8, 14, and 20wk post-iTBS). Metaphor comprehension was improved after iTBS, and the highest scores were obtained 8 weeks later (P=.01). This improvement was correlated with the increase of the right M1 excitability (r=-.86, P=.03) and with the decrease of transcallosal inhibition latency from the left to the right hemisphere (r=-.88, P=.02). Sham yielded no effect (P>.05). Administration of iTBS over the right DLPFC improved metaphor comprehension likely by a long-term influence on brain synaptic plasticity, including improvement of interhemispheric dialogue. More studies are warranted to confirm these findings in larger samples of participants with PD.

  4. Monkey brain cortex imaging by photoacoustic tomography.

    PubMed

    Yang, Xinmai; Wang, Lihong V

    2008-01-01

    Photoacoustic tomography (PAT) is applied to image the brain cortex of a monkey through the intact scalp and skull ex vivo. The reconstructed PAT image shows the major blood vessels on the monkey brain cortex. For comparison, the brain cortex is imaged without the scalp, and then imaged again without the scalp and skull. Ultrasound attenuation through the skull is also measured at various incidence angles. This study demonstrates that PAT of the brain cortex is capable of surviving the ultrasound signal attenuation and distortion caused by a relatively thick skull.

  5. Prefrontal cortex glutamate and extraversion

    PubMed Central

    Schubert, Florian; Jaedke, Maren; Gallinat, Jürgen; Bajbouj, Malek

    2012-01-01

    Extraversion is considered one of the core traits of personality. Low extraversion has been associated with increased vulnerability to affective and anxiety disorders. Brain imaging studies have linked extraversion, approach behaviour and the production of positive emotional states to the dorsolateral prefrontal cortex (DLPFC) and glutamatergic neurotransmission. However, the relationship between extraversion and glutamate in the DLPFC has not been investigated so far. In order to address this issue, absolute glutamate concentrations in the DLPFC and the visual cortex as a control region were measured by 3-Tesla proton magnetic resonance spectroscopy (1H-MRS) in 29 subjects with high and low extraversion. We found increased glutamate levels in the DLPFC of introverts as compared with extraverts. The increased glutamate concentration was specific for the DLPFC and negatively associated with state anxiety. Although preliminary, results indicate altered top-down control of DLPFC due to reduced glutamate concentration as a function of extraversion. Glutamate measurement with 1H-MRS may facilitate the understanding of biological underpinnings of personality traits and psychiatric diseases associated with dysfunctions in approach behaviour and the production of positive emotional states. PMID:22016442

  6. Prefrontal cortex glutamate and extraversion.

    PubMed

    Grimm, Simone; Schubert, Florian; Jaedke, Maren; Gallinat, Jürgen; Bajbouj, Malek

    2012-10-01

    Extraversion is considered one of the core traits of personality. Low extraversion has been associated with increased vulnerability to affective and anxiety disorders. Brain imaging studies have linked extraversion, approach behaviour and the production of positive emotional states to the dorsolateral prefrontal cortex (DLPFC) and glutamatergic neurotransmission. However, the relationship between extraversion and glutamate in the DLPFC has not been investigated so far. In order to address this issue, absolute glutamate concentrations in the DLPFC and the visual cortex as a control region were measured by 3-Tesla proton magnetic resonance spectroscopy (1H-MRS) in 29 subjects with high and low extraversion. We found increased glutamate levels in the DLPFC of introverts as compared with extraverts. The increased glutamate concentration was specific for the DLPFC and negatively associated with state anxiety. Although preliminary, results indicate altered top-down control of DLPFC due to reduced glutamate concentration as a function of extraversion. Glutamate measurement with 1H-MRS may facilitate the understanding of biological underpinnings of personality traits and psychiatric diseases associated with dysfunctions in approach behaviour and the production of positive emotional states.

  7. TOP-DOWN CONTROL OF MOTOR CORTEX ENSEMBLES BY DORSOMEDIAL PREFRONTAL CORTEX

    PubMed Central

    Narayanan, Nandakumar S.; Laubach, Mark

    2007-01-01

    SUMMARY Dorsomedial prefrontal cortex is critical for the temporal control of behavior. Dorsomedial prefrontal cortex might alter neuronal activity in areas such as motor cortex to inhibit temporally inappropriate responses. We tested this hypothesis by recording from neuronal ensembles in rodent dorsomedial prefrontal cortex during a delayed-response task. One-third of dorsomedial prefrontal neurons were significantly modulated during the delay period. The activity of many of these neurons was predictive of premature responding. We then reversibly inactivated dorsomedial prefrontal cortex while recording ensemble activity in motor cortex. Inactivation of dorsomedial prefrontal cortex reduced delay-related firing, but not response-related firing, in motor cortex. Finally, we made simultaneous recordings in dorsomedial prefrontal cortex and motor cortex and found strong delay-related temporal correlations between neurons in the two cortical areas. These data suggest that functional interactions between dorsomedial prefrontal cortex and motor cortex might serve as a top-down control signal that inhibits inappropriate responding. PMID:17145511

  8. Effects of simultaneous bilateral tDCS of the human motor cortex.

    PubMed

    Mordillo-Mateos, Laura; Turpin-Fenoll, Laura; Millán-Pascual, Jorge; Núñez-Pérez, Natalia; Panyavin, Ivan; Gómez-Argüelles, José Maria; Botia-Paniagua, Enrique; Foffani, Guglielmo; Lang, Nicolas; Oliviero, Antonio

    2012-07-01

    Transcranial direct current stimulation (tDCS) is a noninvasive technique that has been investigated as a therapeutic tool for different neurologic disorders. Neuronal excitability can be modified by application of DC in a polarity-specific manner: anodal tDCS increases excitability, while cathodal tDCS decreases excitability. Previous research has shown that simultaneous bilateral tDCS of the human motor cortex facilitates motor performance in the anodal stimulated hemisphere much more than when the same hemisphere is stimulated using unilateral anodal motor cortex tDCS. The main purpose of this study was to determine whether simultaneous bilateral tDCS is able to increase cortical excitability in one hemisphere whereas decreasing cortical excitability in the contralateral hemisphere. To test our hypothesis, cortical excitability before and after bilateral motor cortex tDCS was evaluated. Moreover, the effects of bilateral tDCS were compared with those of unilateral motor cortex tDCS. We evaluated cortical excitability in healthy volunteers before and after unilateral or bilateral tDCS using transcranial magnetic stimulation. We demonstrated that simultaneous application of anodal tDCS over the motor cortex and cathodal tDCS over the contralateral motor cortex induces an increase in cortical excitability on the anodal-stimulated side and a decrease in the cathodal stimulated side. We also used the electrode montage (motor cortex-contralateral orbit) method to compare the bilateral tDCS montage with unilateral tDCS montage. The simultaneous bilateral tDCS induced similar effects to the unilateral montage on the cathode-stimulated side. On the anodal tDCS side, the simultaneous bilateral tDCS seems to be a slightly less robust electrode arrangement compared with the placement of electrodes in the motor cortex-contralateral orbit montage. We also found that intersubject variability of the excitability changes that were induced by the anodal motor cortex tDCS using

  9. Ontogeny of somatostatin receptors in the rat somatosensory cortex

    SciTech Connect

    Gonzalez, B.J.; Leroux, P.; Bodenant, C.; Vaudry, H. )

    1991-03-08

    The distribution and density of SRIF receptors (SRIF-R) were studied during development in the rat somatosensory cortex by in vitro autoradiography with monoiodinated (Tyr0-DTrp8)S14. In 16-day-old fetuses (E16), intense labeling was evident in the intermediate zone of the cortex while low concentrations of SRIF-R were detected in the marginal and ventricular zones. The highest density of SRIF-R was measured in the intermediate zone at E18. At this stage, labeling was also intense in the internal part of the developing cortical plate; in contrast, the concentration of binding sites associated with the marginal and ventricular zones remained relatively low. Profound modifications in the distribution of SRIF-R appeared at birth. In particular, a transient reduction of receptor density occurred in the cortical plate. During the first postnatal week, the density of receptors measured in the intermediate zone decreased gradually; conversely, high levels of SRIF-R were observed in the developing cortical layers (II to VI). At postpartum day 13 (P13), a stage which just precedes completion of cell migration in the parietal cortex, the most intensely labeled regions were layers V-VI and future layers II-III. From P13 to adulthood, the concentrations of SRIF-R decreased in all cortical layers (I to VI) and the pattern of distribution of receptors at P21 was similar to that observed in the adults.

  10. Brain polyphosphoinositide metabolism during focal ischemia in rat cortex

    SciTech Connect

    Lin, T.N.; Liu, T.H.; Xu, J.; Hsu, C.Y.; Sun, G.Y. )

    1991-04-01

    Using a rat model of stroke, we examined the effects of focal cerebral ischemia on the metabolism of polyphosphoinositides by injecting {sup 32}Pi into both the left and right cortices. After equilibration of the label for 2-3 hours, ischemia induced a significant decrease (p less than 0.001) in the concentrations of labeled phosphatidyl 4,5-bisphosphates (66-78%) and phosphatidylinositol 4-phosphate (64-67%) in the right middle cerebral artery cortex of four rats. The phospholipid labeling pattern in the left middle cerebral artery cortex, which sustained only mild ischemia and no permanent tissue damage, was not different from that of two sham-operated controls. However, when {sup 32}Pi was injected 1 hour after the ischemic insult, there was a significant decrease (p less than 0.01) in the incorporation of label into the phospholipids in both cortices of four ischemic rats compared with four sham-operated controls. Furthermore, differences in the phospholipid labeling pattern were observed in the left cortex compared with the sham-operated controls. The change in labeling pattern was attributed to the partial reduction in blood flow following ligation of the common carotid arteries. We provide a sensitive procedure for probing the effects of focal cerebral ischemia on the polyphosphoinositide signaling pathway in the brain, which may play an important role in the pathogenesis of tissue injury.

  11. Dynamics of 3D view invariance in monkey inferotemporal cortex

    PubMed Central

    Ratan Murty, N. Apurva

    2015-01-01

    Rotations in depth are challenging for object vision because features can appear, disappear, be stretched or compressed. Yet we easily recognize objects across views. Are the underlying representations view invariant or dependent? This question has been intensely debated in human vision, but the neuronal representations remain poorly understood. Here, we show that for naturalistic objects, neurons in the monkey inferotemporal (IT) cortex undergo a dynamic transition in time, whereby they are initially sensitive to viewpoint and later encode view-invariant object identity. This transition depended on two aspects of object structure: it was strongest when objects foreshortened strongly across views and were similar to each other. View invariance in IT neurons was present even when objects were reduced to silhouettes, suggesting that it can arise through similarity between external contours of objects across views. Our results elucidate the viewpoint debate by showing that view invariance arises dynamically in IT neurons out of a representation that is initially view dependent. PMID:25609108

  12. Cofilin1 Controls Transcolumnar Plasticity in Dendritic Spines in Adult Barrel Cortex

    PubMed Central

    Tsubota, Tadashi; Okubo-Suzuki, Reiko; Ohashi, Yohei; Tamura, Keita; Ogata, Koshin; Yaguchi, Masae; Matsuyama, Makoto; Inokuchi, Kaoru; Miyashita, Yasushi

    2015-01-01

    During sensory deprivation, the barrel cortex undergoes expansion of a functional column representing spared inputs (spared column), into the neighboring deprived columns (representing deprived inputs) which are in turn shrunk. As a result, the neurons in a deprived column simultaneously increase and decrease their responses to spared and deprived inputs, respectively. Previous studies revealed that dendritic spines are remodeled during this barrel map plasticity. Because cofilin1, a predominant regulator of actin filament turnover, governs both the expansion and shrinkage of the dendritic spine structure in vitro, it hypothetically regulates both responses in barrel map plasticity. However, this hypothesis remains untested. Using lentiviral vectors, we knocked down cofilin1 locally within layer 2/3 neurons in a deprived column. Cofilin1-knocked-down neurons were optogenetically labeled using channelrhodopsin-2, and electrophysiological recordings were targeted to these knocked-down neurons. We showed that cofilin1 knockdown impaired response increases to spared inputs but preserved response decreases to deprived inputs, indicating that cofilin1 dependency is dissociated in these two types of barrel map plasticity. To explore the structural basis of this dissociation, we then analyzed spine densities on deprived column dendritic branches, which were supposed to receive dense horizontal transcolumnar projections from the spared column. We found that spine number increased in a cofilin1-dependent manner selectively in the distal part of the supragranular layer, where most of the transcolumnar projections existed. Our findings suggest that cofilin1-mediated actin dynamics regulate functional map plasticity in an input-specific manner through the dendritic spine remodeling that occurs in the horizontal transcolumnar circuits. These new mechanistic insights into transcolumnar plasticity in adult rats may have a general significance for understanding reorganization of

  13. 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.

  14. Placebo treatment can alter primary visual cortex activity and connectivity.

    PubMed

    Schienle, A; Übel, S; Scharmüller, W

    2014-03-28

    Placebo treatment can alter brain activation in regions implicated in affective processing and cognitive control of emotions. This functional magnetic resonance imaging (fMRI) study investigated whether a placebo can additionally modulate visual cortex activity and connectivity during affective picture perception. The participants underwent a retest design where they were presented with disgusting, fear-eliciting and neutral pictures both with, and without a placebo (inert pill presented with the suggestion that it can reduce disgust symptoms). The placebo provoked a strong decrease in experienced disgust. This was accompanied by a reduced activation of the primary visual cortex, which showed reduced interaction with the amygdala and the insula. Accordingly, placebos are able to affect basic perceptive processes. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Regional variability in age-related loss of neurons from the primary visual cortex and medial prefrontal cortex of male and female rats

    PubMed Central

    Yates, M.A.; Markham, J.A.; Anderson, S.E.; Morris, J.R.; Juraska, J.M.

    2008-01-01

    During aging, changes in the structure of the cerebral cortex of the rat have been seen, but potential changes in neuron number remain largely unexplored. In the present study, stereological methods were used to examine neuron number in the medial prefrontal cortex and primary visual cortex of young adult (85–90 days of age) and aged (19–22 months old) male and female rats in order to investigate any age-related losses. Possible sex differences in aging were also examined since sexually dimorphic patterns of aging have been seen in other measures. An age-related loss of neurons (18–20%), which was mirrored in volume losses, was found to occur in the primary visual cortex in both sexes in all layers except IV. Males, but not females, also lost neurons (15 %) from layer V/VI of the ventral medial prefrontal cortex and showed an overall decrease in volume of this region. In contrast, dorsal medial prefrontal cortex showed no age-related changes. The effects of aging clearly differ among regions of the rat brain and to some degree, between the sexes. PMID:18513705

  16. Triglycerides in the Human Kidney Cortex: Relationship with Body Size

    PubMed Central

    Bobulescu, Ion Alexandru; Lotan, Yair; Zhang, Jianning; Rosenthal, Tara R.; Rogers, John T.; Adams-Huet, Beverley; Sakhaee, Khashayar; Moe, Orson W.

    2014-01-01

    Obesity is associated with increased risk for kidney disease and uric acid nephrolithiasis, but the pathophysiological mechanisms underpinning these associations are incompletely understood. Animal experiments have suggested that renal lipid accumulation and lipotoxicity may play a role, but whether lipid accumulation occurs in humans with increasing body mass index (BMI) is unknown. The association between obesity and abnormal triglyceride accumulation in non-adipose tissues (steatosis) has been described in the liver, heart, skeletal muscle and pancreas, but not in the human kidney. We used a quantitative biochemical assay to quantify triglyceride in normal kidney cortex samples from 54 patients undergoing nephrectomy for localized renal cell carcinoma. In subsets of the study population we evaluated the localization of lipid droplets by Oil Red O staining and measured 16 common ceramide species by mass spectrometry. There was a positive correlation between kidney cortex trigyceride content and BMI (Spearman R = 0.27, P = 0.04). Lipid droplets detectable by optical microscopy had a sporadic distribution but were generally more prevalent in individuals with higher BMI, with predominant localization in proximal tubule cells and to a lesser extent in glomeruli. Total ceramide content was inversely correlated with triglycerides. We postulate that obesity is associated with abnormal triglyceride accumulation (steatosis) in the human kidney. In turn, steatosis and lipotoxicity may contribute to the pathogenesis of obesity-associated kidney disease and nephrolithiasis. PMID:25170827

  17. Reality monitoring impairment in schizophrenia reflects specific prefrontal cortex dysfunction.

    PubMed

    Garrison, Jane R; Fernandez-Egea, Emilio; Zaman, Rashid; Agius, Mark; Simons, Jon S

    2017-01-01

    Reality monitoring impairment is often reported in schizophrenia but the neural basis of this deficit is poorly understood. Difficulties with reality monitoring could be attributable to the same pattern of neural dysfunction as other cognitive deficits that characterize schizophrenia, or might instead represent a separable and dissociable impairment. This question was addressed through direct comparison of behavioral performance and neural activity associated with reality monitoring and working memory in patients with schizophrenia and matched healthy controls. Participants performed a word-pair reality monitoring task and a Sternberg working memory task while undergoing fMRI scanning. Distinct behavioral deficits were observed in the patients during performance of each task, which were associated with separable task- and region-specific dysfunction in the medial anterior prefrontal cortex for reality monitoring and dorsolateral prefrontal cortex for working memory. The results suggest that reality monitoring impairment is a distinct neurocognitive deficit in schizophrenia. The findings are consistent with the presence of a range of dissociable cognitive deficits in schizophrenia which may be associated with variable functional and structural dysconnectivity in underlying processing networks.

  18. Morphogenesis of callosal arbors in the parietal cortex of hamsters.

    PubMed

    Hedin-Pereira, C; Lent, R; Jhaveri, S

    1999-01-01

    The morphogenesis of callosal axons originating in the parietal cortex was studied by anterograde labeling with Phaseolus lectin or biocytin injected in postnatal (P) hamsters aged 7-25 days. Some labeled fibers were serially reconstructed. At P7, some callosal fibers extended as far as the contralateral rhinal fissure, with simple arbors located in the homotopic region of the opposite cortical gray matter, and two or three unbranched sprouts along their trajectory. From P7 to P13, the homotopic arbors became more complex, with branches focused predominantly, but not exclusively, in the supra- and infragranular layers of the homotopic region. Simultaneously, the lateral extension of the trunk axon in the white matter became shorter, finally disappearing by P25. Arbors in the gray matter were either bilaminar (layers 2/3 and 5) or supragranular. A heterotopic projection to the lateral cortex was consistently seen at all ages; the heterotopic arbors follow a similar sequence of events to that seen in homotopic regions. These observations document that callosal axons undergo regressive tangential remodeling during the first postnatal month, as the lateral extension of the trunk fiber gets eliminated. Radially, however, significant arborization occurs in layer-specific locations. The protracted period of morphogenesis suggests a correspondingly long plastic period for this system of cortical fibers.

  19. Ketogenic diet: electrophysiological effects on the normal human cortex.

    PubMed

    Cantello, Roberto; Varrasi, Claudia; Tarletti, Roberto; Cecchin, Michela; D'Andrea, Federico; Veggiotti, Pierangelo; Bellomo, Giorgio; Monaco, Francesco

    2007-09-01

    To explore the cortical electrophysiology of the ketogenic diet (KD) in the normal human. KD is effective against refractory epilepsy, but its precise mechanism is obscure. At the transmitter level, an enhancement of GABA inhibition has often been proposed. We studied eight healthy volunteers undergoing a "classic" KD for 2 weeks. We measured several biochemical variables at baseline (T0), after 1 week (T1) and 2 weeks (T2) of KD, then 3 months after the KD conclusion (T3). Ketosis was quantified as 24-h ketonuria. At the same time, we studied the motor cortical excitability by means of transcranial magnetic stimulation (TMS). We also quantitatively evaluated the EEG signal in search of frequency shifts over the rolandic areas. Significant (p < 0.05) neurophysiological changes appeared at T2. These consisted of a strengthening of short-latency cortical inhibition (SICI), a TMS index which is thought to reflect GABA-A inhibition in the cortex. Then, there was an enhancement of the beta EEG band over the perirolandic region, similar to that following administration of GABA-A agonists. All changes disappeared at T3. A standard, short-term KD affected the cortical physiology of the normal human. The main changes were an augmented SICI and an increased perirolandic beta EEG activity, which are compatible with a lower level of neural excitation within the cortex.

  20. Motor cortex layer 4: less is more

    PubMed Central

    Barbas, Helen; García-Cabezas, Miguel Á.

    2015-01-01

    The stratified motor cortex is variously thought to either lack or contain layer 4. Yamawaki et al. described a functional layer 4 in mouse motor cortex with properties and connections similar to layer 4 in sensory areas. Their results bolster a theoretical framework suggesting all primary cortical areas are equivalent. PMID:25868984

  1. Mapping Prefrontal Cortex Functions in Human Infancy

    ERIC Educational Resources Information Center

    Grossmann, Tobias

    2013-01-01

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

  2. Subspecialization in the human posterior medial cortex

    PubMed Central

    Bzdok, Danilo; Heeger, Adrian; Langner, Robert; Laird, Angela R.; Fox, Peter T.; Palomero-Gallagher, Nicola; Vogt, Brent A.; Zilles, Karl; Eickhoff, Simon B.

    2014-01-01

    The posterior medial cortex (PMC) is particularly poorly understood. Its neural activity changes have been related to highly disparate mental processes. We therefore investigated PMC properties with a data-driven exploratory approach. First, we subdivided the PMC by whole-brain coactivation profiles. Second, functional connectivity of the ensuing PMC regions was compared by task-constrained meta-analytic coactivation mapping (MACM) and task-unconstrained resting-state correlations (RSFC). Third, PMC regions were functionally described by forward/reverse functional inference. A precuneal cluster was mostly connected to the intraparietal sulcus, frontal eye fields, and right temporo-parietal junction; associated with attention and motor tasks. A ventral posterior cingulate cortex (PCC) cluster was mostly connected to the ventromedial prefrontal cortex and middle left inferior parietal cortex (IPC); associated with facial appraisal and language tasks. A dorsal PCC cluster was mostly connected to the dorsomedial prefrontal cortex, anterior/posterior IPC, posterior midcingulate cortex, and left dorsolateral prefrontal cortex; associated with delay discounting. A cluster in the retrosplenial cortex was mostly connected to the anterior thalamus and hippocampus. Furthermore, all PMC clusters were congruently coupled with the default mode network according to task-constrained but not task-unconstrained connectivity. We thus identified distinct regions in the PMC and characterized their neural networks and functional implications. PMID:25462801

  3. Mapping Prefrontal Cortex Functions in Human Infancy

    ERIC Educational Resources Information Center

    Grossmann, Tobias

    2013-01-01

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

  4. Subspecialization in the human posterior medial cortex.

    PubMed

    Bzdok, Danilo; Heeger, Adrian; Langner, Robert; Laird, Angela R; Fox, Peter T; Palomero-Gallagher, Nicola; Vogt, Brent A; Zilles, Karl; Eickhoff, Simon B

    2015-02-01

    The posterior medial cortex (PMC) is particularly poorly understood. Its neural activity changes have been related to highly disparate mental processes. We therefore investigated PMC properties with a data-driven exploratory approach. First, we subdivided the PMC by whole-brain coactivation profiles. Second, functional connectivity of the ensuing PMC regions was compared by task-constrained meta-analytic coactivation mapping (MACM) and task-unconstrained resting-state correlations (RSFC). Third, PMC regions were functionally described by forward/reverse functional inference. A precuneal cluster was mostly connected to the intraparietal sulcus, frontal eye fields, and right temporo-parietal junction; associated with attention and motor tasks. A ventral posterior cingulate cortex (PCC) cluster was mostly connected to the ventromedial prefrontal cortex and middle left inferior parietal cortex (IPC); associated with facial appraisal and language tasks. A dorsal PCC cluster was mostly connected to the dorsomedial prefrontal cortex, anterior/posterior IPC, posterior midcingulate cortex, and left dorsolateral prefrontal cortex; associated with delay discounting. A cluster in the retrosplenial cortex was mostly connected to the anterior thalamus and hippocampus. Furthermore, all PMC clusters were congruently coupled with the default mode network according to task-unconstrained but not task-constrained connectivity. We thus identified distinct regions in the PMC and characterized their neural networks and functional implications. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Addiction and the adrenal cortex

    PubMed Central

    Vinson, Gavin P; Brennan, Caroline H

    2013-01-01

    Substantial evidence shows that the hypophyseal–pituitary–adrenal (HPA) axis and corticosteroids are involved in the process of addiction to a variety of agents, and the adrenal cortex has a key role. In general, plasma concentrations of cortisol (or corticosterone in rats or mice) increase on drug withdrawal in a manner that suggests correlation with the behavioural and symptomatic sequelae both in man and in experimental animals. Corticosteroid levels fall back to normal values in resumption of drug intake. The possible interactions between brain corticotrophin releasing hormone (CRH) and proopiomelanocortin (POMC) products and the systemic HPA, and additionally with the local CRH–POMC system in the adrenal gland itself, are complex. Nevertheless, the evidence increasingly suggests that all may be interlinked and that CRH in the brain and brain POMC products interact with the blood-borne HPA directly or indirectly. Corticosteroids themselves are known to affect mood profoundly and may themselves be addictive. Additionally, there is a heightened susceptibility for addicted subjects to relapse in conditions that are associated with change in HPA activity, such as in stress, or at different times of the day. Recent studies give compelling evidence that a significant part of the array of addictive symptoms is directly attributable to the secretory activity of the adrenal cortex and the actions of corticosteroids. Additionally, sex differences in addiction may also be attributable to adrenocortical function: in humans, males may be protected through higher secretion of DHEA (and DHEAS), and in rats, females may be more susceptible because of higher corticosterone secretion. PMID:23825159

  6. Reduced Numbers of Somatostatin Receptors in the Cerebral Cortex in Alzheimer's Disease

    NASA Astrophysics Data System (ADS)

    Flint Beal, M.; Mazurek, Michael F.; Tran, Vinh T.; Chattha, Geetinder; Bird, Edward D.; Martin, Joseph B.

    1985-07-01

    Somatostatin receptor concentrations were measured in patients with Alzheimer's disease and controls. In the frontal cortex (Brodmann areas 6, 9, and 10) and temporal cortex (Brodmann area 21), the concentrations of somatostatin in receptors in the patients were reduced to approximately 50 percent of control values. A 40 percent reduction was seen in the hippocampus, while no significant changes were found in the cingulate cortex, postcentral gyrus, temporal pole, and superior temporal gyrus. Scatchard analysis showed a reduction in receptor number rather than a change in affinity. Somatostatin-like immunoreactivity was significantly reduced in both the frontal and temporal cortex. Somatostatin-like immunoreactivity was linearly related to somatostatin-receptor binding in the cortices of Alzheimer's patients. These findings may reflect degeneration of postsynaptic neurons or cortical afferents in the patients' cerebral cortices. Alternatively, decreased somatostatinlike immunoreactivity in Alzheimer's disease might indicate increased release of somatostatin and down regulation of postsynaptic receptors.

  7. Damage to Temporo-Parietal Cortex Decreases Incidental Activation of Thematic Relations during Spoken Word Comprehension

    ERIC Educational Resources Information Center

    Mirman, Daniel; Graziano, Kristen M.

    2012-01-01

    Both taxonomic and thematic semantic relations have been studied extensively in behavioral studies and there is an emerging consensus that the anterior temporal lobe plays a particularly important role in the representation and processing of taxonomic relations, but the neural basis of thematic semantics is less clear. We used eye tracking to…

  8. Damage to Temporo-Parietal Cortex Decreases Incidental Activation of Thematic Relations during Spoken Word Comprehension

    ERIC Educational Resources Information Center

    Mirman, Daniel; Graziano, Kristen M.

    2012-01-01

    Both taxonomic and thematic semantic relations have been studied extensively in behavioral studies and there is an emerging consensus that the anterior temporal lobe plays a particularly important role in the representation and processing of taxonomic relations, but the neural basis of thematic semantics is less clear. We used eye tracking to…

  9. Decreased motor cortex excitability mirrors own hand disembodiment during the rubber hand illusion

    PubMed Central

    della Gatta, Francesco; Garbarini, Francesca; Puglisi, Guglielmo; Leonetti, Antonella; Berti, Annamaria; Borroni, Paola

    2016-01-01

    During the rubber hand illusion (RHI), subjects experience an artificial hand as part of their own body, while the real hand is subject to a sort of 'disembodiment'. Can this altered belief about the body also affect physiological mechanisms involved in body-ownership, such as motor control? Here we ask whether the excitability of the motor pathways to the real (disembodied) hand are affected by the illusion. Our results show that the amplitude of the motor-evoked potentials recorded from the real hand is significantly reduced, with respect to baseline, when subjects in the synchronous (but not in the asynchronous) condition experience the fake hand as their own. This finding contributes to the theoretical understanding of the relationship between body-ownership and motor system, and provides the first physiological evidence that a significant drop in motor excitability in M1 hand circuits accompanies the disembodiment of the real hand during the RHI experience. DOI: http://dx.doi.org/10.7554/eLife.14972.001 PMID:27760692

  10. Alterations of motor performance and brain cortex mitochondrial function during ethanol hangover.

    PubMed

    Bustamante, Juanita; Karadayian, Analia G; Lores-Arnaiz, Silvia; Cutrera, Rodolfo A

    2012-08-01

    Ethanol has been known to affect various behavioral parameters in experimental animals, even several hours after ethanol (EtOH) is absent from blood circulation, in the period known as hangover. The aim of this study was to assess the effects of acute ethanol hangover on motor performance in association with the brain cortex energetic metabolism. Evaluation of motor performance and brain cortex mitochondrial function during alcohol hangover was performed in mice 6 hours after a high ethanol dose (hangover onset). Animals were injected i.p. either with saline (control group) or with ethanol (3.8 g/kg BW) (hangover group). Ethanol hangover group showed a bad motor performance compared with control animals (p < .05). Oxygen uptake in brain cortex mitochondria from hangover animals showed a 34% decrease in the respiratory control rate as compared with the control group. Mitochondrial complex activities were decreased being the complex I-III the less affected by the hangover condition; complex II-III was markedly decreased by ethanol hangover showing 50% less activity than controls. Complex IV was 42% decreased as compared with control animals. Hydrogen peroxide production was 51% increased in brain cortex mitochondria from the hangover group, as compared with the control animals. Quantification of the mitochondrial transmembrane potential indicated that ethanol injected animals presented 17% less ability to maintain the polarized condition as compared with controls. These results indicate that a clear decrease in proton motive force occurs in brain cortex mitochondria during hangover conditions. We can conclude that a decreased motor performance observed in the hangover group of animals could be associated with brain cortex mitochondrial dysfunction and the resulting impairment of its energetic metabolism.

  11. Maternal Loss of Ube3a Impairs Experience-Driven Dendritic Spine Maintenance in the Developing Visual Cortex.

    PubMed

    Kim, Hyojin; Kunz, Portia A; Mooney, Richard; Philpot, Benjamin D; Smith, Spencer L

    2016-04-27

    Dendritic spines are a morphological feature of the majority of excitatory synapses in the mammalian neocortex and are motile structures with shapes and lifetimes that change throughout development. Proper cortical development and function, including cortical contributions to learning and memory formation, require appropriate experience-dependent dendritic spine remodeling. Dendritic spine abnormalities have been reported for many neurodevelopmental disorders, including Angelman syndrome (AS), which is caused by the loss of the maternally inherited UBE3A allele (encoding ubiquitin protein ligase E3A). Prior studies revealed that UBE3A protein loss leads to reductions in dendritic spine density and diminished excitatory synaptic transmission. However, the decrease in spine density could come from either a reduction in spine formation or an increase in spine elimination. Here, we used acute and longitudinal in vivo two-photon microscopy to investigate developmental and experience-dependent changes in the numbers, dynamics, and morphology of layer 5 pyramidal neuron apical dendritic spines in the primary visual cortex of control and AS model mice (Ube3a(m-/p+) mice). We found that neurons in AS model mice undergo a greater elimination of dendritic spines than wild-type mice during the end of the first postnatal month. However, when raised in darkness, spine density and dynamics were indistinguishable between control and AS model mice, which indicates that decreased spine density in AS model mice reflects impaired experience-driven spine maintenance. Our data thus demonstrate an experience-dependent anatomical substrate by which the loss of UBE3A reduces dendritic spine density and disrupts cortical circuitry. Reduced dendritic spine densities are common in the neurodevelopmental disorder Angelman syndrome (AS). Because prior reports were based on postmortem tissue, it was unknown whether this anatomical deficit arises from decreased spine formation and/or increased

  12. Stream segregation in the anesthetized auditory cortex

    PubMed Central

    Scholes, Chris; Palmer, Alan R.; Sumner, Christian J.

    2015-01-01

    Auditory stream segregation describes the way that sounds are perceptually segregated into groups or streams on the basis of perceptual attributes such as pitch or spectral content. For sequences of pure tones, segregation depends on the tones' proximity in frequency and time. In the auditory cortex (and elsewhere) responses to sequences of tones are dependent on stimulus conditions in a similar way to the perception of these stimuli. However, although highly dependent on stimulus conditions, perception is also clearly influenced by factors unrelated to the stimulus, such as attention. Exactly how ‘bottom-up’ sensory processes and non-sensory ‘top-down’ influences interact is still not clear. Here, we recorded responses to alternating tones (ABAB …) of varying frequency difference (FD) and rate of presentation (PR) in the auditory cortex of anesthetized guinea-pigs. These data complement previous studies, in that top-down processing resulting from conscious perception should be absent or at least considerably attenuated. Under anesthesia, the responses of cortical neurons to the tone sequences adapted rapidly, in a manner sensitive to both the FD and PR of the sequences. While the responses to tones at frequencies more distant from neuron best frequencies (BFs) decreased as the FD increased, the responses to tones near to BF increased, consistent with a release from adaptation, or forward suppression. Increases in PR resulted in reductions in responses to all tones, but the reduction was greater for tones further from BF. Although asymptotically adapted responses to tones showed behavior that was qualitatively consistent with perceptual stream segregation, responses reached asymptote within 2 s, and responses to all tones were very weak at high PRs (>12 tones per second). A signal-detection model, driven by the cortical population response, made decisions that were dependent on both FD and PR in ways consistent with perceptual stream segregation. This

  13. Stream segregation in the anesthetized auditory cortex.

    PubMed

    Scholes, Chris; Palmer, Alan R; Sumner, Christian J

    2015-10-01

    Auditory stream segregation describes the way that sounds are perceptually segregated into groups or streams on the basis of perceptual attributes such as pitch or spectral content. For sequences of pure tones, segregation depends on the tones' proximity in frequency and time. In the auditory cortex (and elsewhere) responses to sequences of tones are dependent on stimulus conditions in a similar way to the perception of these stimuli. However, although highly dependent on stimulus conditions, perception is also clearly influenced by factors unrelated to the stimulus, such as attention. Exactly how 'bottom-up' sensory processes and non-sensory 'top-down' influences interact is still not clear. Here, we recorded responses to alternating tones (ABAB …) of varying frequency difference (FD) and rate of presentation (PR) in the auditory cortex of anesthetized guinea-pigs. These data complement previous studies, in that top-down processing resulting from conscious perception should be absent or at least considerably attenuated. Under anesthesia, the responses of cortical neurons to the tone sequences adapted rapidly, in a manner sensitive to both the FD and PR of the sequences. While the responses to tones at frequencies more distant from neuron best frequencies (BFs) decreased as the FD increased, the responses to tones near to BF increased, consistent with a release from adaptation, or forward suppression. Increases in PR resulted in reductions in responses to all tones, but the reduction was greater for tones further from BF. Although asymptotically adapted responses to tones showed behavior that was qualitatively consistent with perceptual stream segregation, responses reached asymptote within 2 s, and responses to all tones were very weak at high PRs (>12 tones per second). A signal-detection model, driven by the cortical population response, made decisions that were dependent on both FD and PR in ways consistent with perceptual stream segregation. This

  14. Vocalization Induced CFos Expression in Marmoset Cortex

    PubMed Central

    Miller, Cory T.; DiMauro, Audrey; Pistorio, Ashley; Hendry, Stewart; Wang, Xiaoqin

    2010-01-01

    All non-human primates communicate with conspecifics using vocalizations, a system involving both the production and perception of species-specific vocal signals. Much of the work on the neural basis of primate vocal communication in cortex has focused on the sensory processing of vocalizations, while relatively little data are available for vocal production. Earlier physiological studies in squirrel monkeys had shed doubts on the involvement of primate cortex in vocal behaviors. The aim of the present study was to identify areas of common marmoset (Callithrix jacchus) cortex that are potentially involved in vocal communication. In this study, we quantified cFos expression in three areas of marmoset cortex – frontal, temporal (auditory), and medial temporal – under various vocal conditions. Specifically, we examined cFos expression in these cortical areas during the sensory, motor (vocal production), and sensory–motor components of vocal communication. Our results showed an increase in cFos expression in ventrolateral prefrontal cortex as well as the medial and lateral belt areas of auditory cortex in the vocal perception condition. In contrast, subjects in the vocal production condition resulted in increased cFos expression only in dorsal premotor cortex. During the sensory–motor condition (antiphonal calling), subjects exhibited cFos expression in each of the above areas, as well as increased expression in perirhinal cortex. Overall, these results suggest that various cortical areas outside primary auditory cortex are involved in primate vocal communication. These findings pave the way for further physiological studies of the neural basis of primate vocal communication. PMID:21179582

  15. Obesity Decreases Perioperative Tissue Oxygenation

    PubMed Central

    Kabon, Barbara; Nagele, Angelika; Reddy, Dayakar; Eagon, Chris; Fleshman, James W.; Sessler, Daniel I.; Kurz, Andrea

    2005-01-01

    Background: Obesity is an important risk factor for surgical site infections. The incidence of surgical wound infections is directly related to tissue perfusion and oxygenation. Fat tissue mass expands without a concomitant increase in blood flow per cell, which might result in a relative hypoperfusion with decreased tissue oxygenation. Consequently, we tested the hypotheses that perioperative tissue oxygen tension is reduced in obese surgical patients. Furthermore, we compared the effect of supplemental oxygen administration on tissue oxygenation in obese and non-obese patients. Methods: Forty-six patients undergoing major abdominal surgery were assigned to one of two groups according to their body mass index (BMI): BMI < 30 kg/m2 (non-obese) and BMI ≥ 30 kg/m2 (obese). Intraoperative oxygen administration was adjusted to arterial oxygen tensions of ≈150 mmHg and ≈300 mmHg in random order. Anesthesia technique and perioperative fluid management were standardized. Subcutaneous tissue oxygen tension was measured with a polarographic electrode positioned within a subcutaneous tonometer in the lateral upper arm during surgery, in the recovery room, and on the first postoperative day. Postoperative tissue oxygen was also measured adjacent to the wound. Data were compared with unpaired two tailed t-tests and Wilcoxon rank-sum tests; P < 0.05 was considered statistically significant. Results: Intraoperative subcutaneous tissue oxygen tension was significantly less in the obese patients at baseline (36 vs. 57 mmHg, P = 0.002) and with supplemental oxygen administration (47 vs. 76 mmHg, P = 0.014). Immediate postoperative tissue oxygen tension was also significantly less in subcutaneous tissue of the upper arm (43 vs. 54 mmHg, P = 0.011) as well as near the incision (42 vs. 62 mmHg, P = 0.012) in obese patients. In contrast, tissue oxygen tension was comparable in each group on the first postoperative morning. Conclusion: Wound and tissue hypoxia were common in obese

  16. Functional specialization in rat occipital and temporal visual cortex

    PubMed Central

    Vermaercke, Ben; Gerich, Florian J.; Ytebrouck, Ellen; Arckens, Lutgarde; Van den Bergh, Gert

    2014-01-01

    Recent studies have revealed a surprising degree of functional specialization in rodent visual cortex. Anatomically, suggestions have been made about the existence of hierarchical pathways with similarities to the ventral and dorsal pathways in primates. Here we aimed to characterize some important functional properties in part of the supposed “ventral” pathway in rats. We investigated the functional properties along a progression of five visual areas in awake rats, from primary visual cortex (V1) over lateromedial (LM), latero-intermediate (LI), and laterolateral (LL) areas up to the newly found lateral occipito-temporal cortex (TO). Response latency increased >20 ms from areas V1/LM/LI to areas LL and TO. Orientation and direction selectivity for the used grating patterns increased gradually from V1 to TO. Overall responsiveness and selectivity to shape stimuli decreased from V1 to TO and was increasingly dependent upon shape motion. Neural similarity for shapes could be accounted for by a simple computational model in V1, but not in the other areas. Across areas, we find a gradual change in which stimulus pairs are most discriminable. Finally, tolerance to position changes increased toward TO. These findings provide unique information about possible commonalities and differences between rodents and primates in hierarchical cortical processing. PMID:24990566

  17. Five key factors determining pairwise correlations in visual cortex

    PubMed Central

    Sahani, Maneesh; Carandini, Matteo

    2015-01-01

    The responses of cortical neurons to repeated presentation of a stimulus are highly variable, yet correlated. These “noise correlations” reflect a low-dimensional structure of population dynamics. Here, we examine noise correlations in 22,705 pairs of neurons in primary visual cortex (V1) of anesthetized cats, during ongoing activity and in response to artificial and natural visual stimuli. We measured how noise correlations depend on 11 factors. Because these factors are themselves not independent, we distinguished their influences using a nonlinear additive model. The model revealed that five key factors play a predominant role in determining pairwise correlations. Two of these are distance in cortex and difference in sensory tuning: these are known to decrease correlation. A third factor is firing rate: confirming most earlier observations, it markedly increased pairwise correlations. A fourth factor is spike width: cells with a broad spike were more strongly correlated amongst each other. A fifth factor is spike isolation: neurons with worse isolation were more correlated, even if they were recorded on different electrodes. For pairs of neurons with poor isolation, this last factor was the main determinant of correlations. These results were generally independent of stimulus type and timescale of analysis, but there were exceptions. For instance, pairwise correlations depended on difference in orientation tuning more during responses to gratings than to natural stimuli. These results consolidate disjoint observations in a vast literature on pairwise correlations and point towards regularities of population coding in sensory cortex. PMID:26019310

  18. Structural development and dorsoventral maturation of the medial entorhinal cortex.

    PubMed

    Ray, Saikat; Brecht, Michael

    2016-04-02

    We investigated the structural development of superficial-layers of medial entorhinal cortex and parasubiculum in rats. The grid-layout and cholinergic-innervation of calbindin-positive pyramidal-cells in layer-2 emerged around birth while reelin-positive stellate-cells were scattered throughout development. Layer-3 and parasubiculum neurons had a transient calbindin-expression, which declined with age. Early postnatally, layer-2 pyramidal but not stellate-cells co-localized with doublecortin - a marker of immature neurons - suggesting delayed functional-maturation of pyramidal-cells. Three observations indicated a dorsal-to-ventral maturation of entorhinal cortex and parasubiculum: (i) calbindin-expression in layer-3 neurons decreased progressively from dorsal-to-ventral, (ii) doublecortin in layer-2 calbindin-positive-patches disappeared dorsally before ventrally, and (iii) wolframin-expression emerged earlier in dorsal than ventral parasubiculum. The early appearance of calbindin-pyramidal-grid-organization in layer-2 suggests that this pattern is instructed by genetic information rather than experience. Superficial-layer-microcircuits mature earlier in dorsal entorhinal cortex, where small spatial-scales are represented. Maturation of ventral-entorhinal-microcircuits - representing larger spatial-scales - follows later around the onset of exploratory behavior.

  19. Structural development and dorsoventral maturation of the medial entorhinal cortex

    PubMed Central

    Ray, Saikat; Brecht, Michael

    2016-01-01

    We investigated the structural development of superficial-layers of medial entorhinal cortex and parasubiculum in rats. The grid-layout and cholinergic-innervation of calbindin-positive pyramidal-cells in layer-2 emerged around birth while reelin-positive stellate-cells were scattered throughout development. Layer-3 and parasubiculum neurons had a transient calbindin-expression, which declined with age. Early postnatally, layer-2 pyramidal but not stellate-cells co-localized with doublecortin – a marker of immature neurons – suggesting delayed functional-maturation of pyramidal-cells. Three observations indicated a dorsal-to-ventral maturation of entorhinal cortex and parasubiculum: (i) calbindin-expression in layer-3 neurons decreased progressively from dorsal-to-ventral, (ii) doublecortin in layer-2 calbindin-positive-patches disappeared dorsally before ventrally, and (iii) wolframin-expression emerged earlier in dorsal than ventral parasubiculum. The early appearance of calbindin-pyramidal-grid-organization in layer-2 suggests that this pattern is instructed by genetic information rather than experience. Superficial-layer-microcircuits mature earlier in dorsal entorhinal cortex, where small spatial-scales are represented. Maturation of ventral-entorhinal-microcircuits – representing larger spatial-scales – follows later around the onset of exploratory behavior. DOI: http://dx.doi.org/10.7554/eLife.13343.001 PMID:27036175

  20. Transformation of Cortex-wide Emergent Properties during Motor Learning.

    PubMed

    Makino, Hiroshi; Ren, Chi; Liu, Haixin; Kim, An Na; Kondapaneni, Neehar; Liu, Xin; Kuzum, Duygu; Komiyama, Takaki

    2017-05-17

    Learning involves a transformation of brain-wide operation dynamics. However, our understanding of learning-related changes in macroscopic dynamics is limited. Here, we monitored cortex-wide activity of the mouse brain using wide-field calcium imaging while the mouse learned a motor task over weeks. Over learning, the sequential activity across cortical modules became temporally more compressed, and its trial-by-trial variability decreased. Moreover, a new flow of activity emerged during learning, originating from premotor cortex (M2), and M2 became predictive of the activity of many other modules. Inactivation experiments showed that M2 is critical for the post-learning dynamics in the cortex-wide activity. Furthermore, two-photon calcium imaging revealed that M2 ensemble activity also showed earlier activity onset and reduced variability with learning, which was accompanied by changes in the activity-movement relationship. These results reveal newly emergent properties of macroscopic cortical dynamics during motor learning and highlight the importance of M2 in controlling learned movements. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Transport of L-carnitine in isolated cerebral cortex neurons.

    PubMed

    Wawrzeńczyk, A; Sacher, A; Mac, M; Nałecz, M J; Nałecz, K A

    2001-04-01

    The accumulation of carnitine was measured in cerebral cortex neurons isolated from adult rat brain. This process was found to be lowered by 40% after preincubation with ouabain and with SH-group reagents (N-ethylmaleimide and mersalyl). The initial velocity of carnitine transport was found to be inhibited by 4-aminobutyrate (GABA) in a competitive way (Ki = 20.9 +/- 2.4 mM). However, of various inhibitors of GABA transporters, only nipecotic acid and very high concentrations of 1-[2-([(diphenylmethylene)amino]oxy)ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride (NO-711) acid decreased carnitine accumulation while betaine, taurine and beta-alanine had no effect. The GABA transporters expressed in Xenopus laevis oocytes did not transport carnitine. Moreover, carnitine was not observed to diminish the accumulation of GABA in cerebral cortex neurons, which further excluded a possible involvement of the GABA transporter GAT1 in the process of carnitine accumulation, despite the expression of this protein in the cells under study. The absence of carnitine transporter OCTN2 in rat cerebral cortex neurons (K. A. Nałecz, D. Dymna, J. E. Mroczkowska, A. Broër, S. Broër, M. J. Nałecz and R. Cecchelli, unpublished results), together with the insensitivity of carnitine accumulation towards betaines, implies that a novel transporting protein is present in these cells.

  2. Color vision, cones, and color-coding in the cortex.

    PubMed

    Conway, Bevil R

    2009-06-01

    Color processing begins with the absorption of light by cone photoreceptors, and progresses through a series of hierarchical stages: Retinal signals carrying color information are transmitted through the lateral geniculate nucleus of the thalamus (LGN) up to the primary visual cortex (V1). From V1, the signals are processed by the second visual area (V2); then by cells located in subcompartments ("globs") within the posterior inferior temporal (PIT) cortex, a brain region that encompasses area V4 and brain regions immediately anterior to V4. Color signals are then processed by regions deep within the inferior temporal (IT) cortex including area TE. As a heuristic, one can consider each of these stages to be involved in constructing a distinct aspect of the color percept. The three cone types are the basis for trichromacy; retinal ganglion cells that respond in an opponent fashion to activation of different cone classes are the basis for color opponency (these "cone-opponent" cells increase their firing rate above baseline to activation of one cone class and decrease their firing rate below baseline to activation of a different cone class); double-opponent neurons in the V1 generate local color contrast and are the building blocks for color constancy; glob cells elaborate the perception of hue; and IT integrates color perception in the context of behavior. Finally, though nothing is known, these signals presumably interface with motor programs and emotional centers of the brain to mediate the widely acknowledged emotional salience of color.

  3. Parental anxiety and concern for children undergoing dermatological surgery.

    PubMed

    Hoetzenecker, Wolfram; Guenova, Emmanuella; Krug, Markus; Goetz, Angelika; Amarov, Boyko; Haefner, Hans-Martin; Breuninger, Helmut

    2014-10-01

    Parents experience anxiety and concern about their children's anesthesia and surgeries, which can adversely affect the children's outcomes. Therefore, it is important to identify the factors that influence parental fear. Because dermatological surgery is often performed in young children, we examined how a child's age and the size of the dermatological surgical area affected the levels of parental anxiety and concern. The parents' levels of anxiety and concern were accessed by parental self-reports in a prospective observational study of 106 children undergoing dermatological surgery. Correlation analysis showed that the level of parental anxiety decreased with the child's age. In contrast, the level of parental anxiety increased with the size of the surgical area. Our findings thus indicate that parents whose children undergo large-sized surgeries at a young age are at high risk. This result should be considered when performing dermatological surgery in children.

  4. Medial perirhinal cortex disambiguates confusable objects.

    PubMed

    Kivisaari, Sasa L; Tyler, Lorraine K; Monsch, Andreas U; Taylor, Kirsten I

    2012-12-01

    Our brain disambiguates the objects in our cluttered visual world seemingly effortlessly, enabling us to understand their significance and to act appropriately. The role of anteromedial temporal structures in this process, particularly the perirhinal cortex, is highly controversial. In some accounts, the perirhinal cortex is necessary for differentiating between perceptually and semantically confusable objects. Other models claim that the perirhinal cortex neither disambiguates perceptually confusable objects nor plays a unique role in semantic processing. One major hurdle to resolving this central debate is the fact that brain damage in human patients typically encompasses large portions of the anteromedial temporal lobe, such that the identification of individual substructures and precise neuroanatomical locus of the functional impairments has been difficult. We tested these competing accounts in patients with Alzheimer's disease with varying degrees of atrophy in anteromedial structures, including the perirhinal cortex. To assess the functional contribution of each anteromedial temporal region separately, we used a detailed region of interest approach. From each participant, we obtained magnetic resonance imaging scans and behavioural data from a picture naming task that contrasted naming performance with living and non-living things as a way of manipulating perceptual and semantic confusability; living things are more similar to one another than non-living things, which have more distinctive features. We manually traced neuroanatomical regions of interest on native-space cortical surface reconstructions to obtain mean thickness estimates for the lateral and medial perirhinal cortex and entorhinal cortex. Mean cortical thickness in each region of interest, and hippocampal volume, were submitted to regression analyses predicting naming performance. Importantly, atrophy of the medial perirhinal cortex, but not lateral perirhinal cortex, entorhinal cortex or

  5. Immediate hemodynamic response to furosemide in patients undergoing chronic hemodialysis.

    PubMed

    Schmieder, R E; Messerli, F H; deCarvalho, J G; Husserl, F E

    1987-01-01

    To evaluate the effect of furosemide on cardiovascular hemodynamics in patients with end-stage renal failure, we studied ten patients undergoing hemodialysis three times a week. Arterial pressure, heart rate, and cardiac output (indocyanine green dye) were measured in triplicate; total peripheral resistance and central blood volume were calculated by standard formulas. Hemodynamics were determined at baseline and 5, 10, 15, and 30 minutes after intravenous (IV) bolus injection of furosemide 60 mg. Furosemide produced a decrease in central blood volume of -13% +/- 2.2% from pretreatment values (P less than .01) that was most pronounced five minutes after injection, together with a fall in cardiac output (from 6.76 +/- 0.59 to 6.17 +/- 0.52 L/min, P less than .10). Stroke volume decreased with a maximum fall occurring after 15 minutes (from 84 +/- 7 to 79 +/- 7 mL/min, P less than .05), and total peripheral resistance increased (from 15.8 +/- 2.1 to 17.8 +/- 2.3 units, P less than .05) after furosemide. Arterial pressure and heart rate did not change. The decrease in central blood volume reflects a shift of the total blood volume from the cardiopulmonary circulation to the periphery, suggesting dilation of the peripheral venous bed. Thus, even in patients undergoing hemodialysis, furosemide acutely decreases left ventricular preload by venous dilation and should therefore prove to be beneficial in acute volume overload.

  6. Developmental role of the cell adhesion molecule Contactin-6 in the cerebral cortex and hippocampus.

    PubMed

    Zuko, Amila; Oguro-Ando, Asami; van Dijk, Roland; Gregorio-Jordan, Sara; van der Zwaag, Bert; Burbach, J Peter H

    2016-07-03

    The gene encoding the neural cell adhesion molecule Contactin-6 (Cntn6 a.k.a. NB-3) has been implicated as an autism risk gene, suggesting that its mutation is deleterious to brain development. Due to its GPI-anchor at Cntn6 may exert cell adhesion/receptor functions in complex with other membrane proteins, or serve as a ligand. We aimed to uncover novel phenotypes related to Cntn6 functions during development in the cerebral cortex of adult Cntn6(-/-) mice. We first determined Cntn6 protein and mRNA expression in the cortex, thalamic nuclei and the hippocampus at P14, which decreased specifically in the cortex at adult stages. Neuroanatomical analysis demonstrated a significant decrease of Cux1+ projection neurons in layers II-IV and an increase of FoxP2+ projection neurons in layer VI in the visual cortex of adult Cntn6(-/-) mice compared to wild-type controls. Furthermore, the number of parvalbumin+ (PV) interneurons was decreased in Cntn6(-/-) mice, while the amount of NPY+ interneurons remained unchanged. In the hippocampus the delineation and outgrowth of mossy fibers remained largely unchanged, except for the observation of a larger suprapyramidal bundle. The observed abnormalities in the cerebral cortex and hippocampus of Cntn6(-/-) mice suggests that Cntn6 serves developmental functions involving cell survival, migration and fasciculation. Furthermore, these data suggest that Cntn6 engages in both trans- and cis-interactions and may be involved in larger protein interaction networks.

  7. Human posterior auditory cortex gates novel sounds to consciousness

    PubMed Central

    Jääskeläinen, Iiro P.; Ahveninen, Jyrki; Bonmassar, Giorgio; Dale, Anders M.; Ilmoniemi, Risto J.; Levänen, Sari; Lin, Fa-Hsuan; May, Patrick; Melcher, Jennifer; Stufflebeam, Steven; Tiitinen, Hannu; Belliveau, John W.

    2004-01-01

    Life or death in hostile environments depends crucially on one's ability to detect and gate novel sounds to awareness, such as that of a twig cracking under the paw of a stalking predator in a noisy jungle. Two distinct auditory cortex processes have been thought to underlie this phenomenon: (i) attenuation of the so-called N1 response with repeated stimulation and (ii) elicitation of a mismatch negativity response (MMN) by changes in repetitive aspects of auditory stimulation. This division has been based on previous studies suggesting that, unlike for the N1, repetitive “standard” stimuli preceding a physically different “novel” stimulus constitute a prerequisite to MMN elicitation, and that the source loci of MMN and N1 are different. Contradicting these findings, our combined electromagnetic, hemodynamic, and psychophysical data indicate that the MMN is generated as a result of differential adaptation of anterior and posterior auditory cortex N1 sources by preceding auditory stimulation. Early (≈85 ms) neural activity within posterior auditory cortex is adapted as sound novelty decreases. This alters the center of gravity of electromagnetic N1 source activity, creating an illusory difference between N1 and MMN source loci when estimated by using equivalent current dipole fits. Further, our electroencephalography data show a robust MMN after a single standard event when the interval between two consecutive novel sounds is kept invariant. Our converging findings suggest that transient adaptation of feature-specific neurons within human posterior auditory cortex filters superfluous sounds from entering one's awareness. PMID:15096618

  8. Preparatory attention in visual cortex.

    PubMed

    Battistoni, Elisa; Stein, Timo; Peelen, Marius V

    2017-05-01

    Top-down attention is the mechanism that allows us to selectively process goal-relevant aspects of a scene while ignoring irrelevant aspects. A large body of research has characterized the effects of attention on neural activity evoked by a visual stimulus. However, attention also includes a preparatory phase before stimulus onset in which the attended dimension is internally represented. Here, we review neurophysiological, functional magnetic resonance imaging, magnetoencephalography, electroencephalography, and transcranial magnetic stimulation (TMS) studies investigating the neural basis of preparatory attention, both when attention is directed to a location in space and when it is directed to nonspatial stimulus attributes (content-based attention) ranging from low-level features to object categories. Results show that both spatial and content-based attention lead to increased baseline activity in neural populations that selectively code for the attended attribute. TMS studies provide evidence that this preparatory activity is causally related to subsequent attentional selection and behavioral performance. Attention thus acts by preactivating selective neurons in the visual cortex before stimulus onset. This appears to be a general mechanism that can operate on multiple levels of representation. We discuss the functional relevance of this mechanism, its limitations, and its relation to working memory, imagery, and expectation. We conclude by outlining open questions and future directions. © 2017 New York Academy of Sciences.

  9. Space and the parietal cortex

    PubMed Central

    Husain, Masud; Nachev, Parashkev

    2007-01-01

    Current views of the parietal cortex have difficulty accommodating the human inferior parietal lobe (IPL) within a simple dorsal versus ventral stream dichotomy. In humans, lesions of the right IPL often lead to syndromes such as hemispatial neglect that are seemingly in accord with the proposal that this region has a crucial role in spatial processing. However, recent imaging and lesion studies have revealed that inferior parietal regions have non-spatial functions, such as in sustaining attention, detecting salient events embedded in a sequence of events and controlling attention over time. Here, we review these findings and show that spatial processes and the visual guidance of action are only part of the repertoire of parietal functions. Although sub-regions in the human superior parietal lobe and intraparietal sulcus contribute to vision-for-action and spatial functions, more inferior parietal regions have distinctly non-spatial attributes that are neither conventionally ‘dorsal’ nor conventionally ‘ventral’ in nature. PMID:17134935

  10. Developmental changes in propagation patterns and transmitter dependence of waves of spontaneous activity in the mouse cerebral cortex

    PubMed Central

    Conhaim, Jay; Easton, Curtis R; Becker, Matthew I; Barahimi, Mitra; Cedarbaum, Emily R; Moore, Jennifer G; Mather, Luke F; Dabagh, Sarah; Minter, Daniel J; Moen, Samantha P; Moody, William J

    2011-01-01

    Abstract Waves of spontaneous electrical activity propagate across many regions of the central nervous system during specific stages of early development. The patterns of wave propagation are critical in the activation of many activity-dependent developmental programs. It is not known how the mechanisms that initiate and propagate spontaneous waves operate during periods in which major changes in neuronal structure and function are taking place. We have recently reported that spontaneous waves of activity propagate across the neonatal mouse cerebral cortex and that these waves are initiated at pacemaker sites in the septal nucleus and ventral cortex. Here we show that spontaneous waves occur between embryonic day 18 (E18) and postnatal day 12 (P12), and that during that period they undergo major changes in transmitter dependence and propagation patterns. At early stages, spontaneous waves are largely GABA dependent and are mostly confined to the septum and ventral cortex. As development proceeds, wave initiation depends increasingly on AMPA-type glutamate receptors, and an ever increasing fraction of waves propagate into the dorsal cortex. The initiation sites and restricted propagation of waves at early stages are highly correlated with the position of GABAergic neurons in the cortex. The later switch to a glutamate-based mechanism allows propagation of waves into the dorsal cortex, and appears to be a compensatory mechanism that ensures continued wave generation even as GABA transmission becomes inhibitory. PMID:21486817

  11. Developmental changes in propagation patterns and transmitter dependence of waves of spontaneous activity in the mouse cerebral cortex.

    PubMed

    Conhaim, Jay; Easton, Curtis R; Becker, Matthew I; Barahimi, Mitra; Cedarbaum, Emily R; Moore, Jennifer G; Mather, Luke F; Dabagh, Sarah; Minter, Daniel J; Moen, Samantha P; Moody, William J

    2011-05-15

    Waves of spontaneous electrical activity propagate across many regions of the central nervous system during specific stages of early development. The patterns of wave propagation are critical in the activation of many activity-dependent developmental programs. It is not known how the mechanisms that initiate and propagate spontaneous waves operate during periods in which major changes in neuronal structure and function are taking place. We have recently reported that spontaneous waves of activity propagate across the neonatal mouse cerebral cortex and that these waves are initiated at pacemaker sites in the septal nucleus and ventral cortex. Here we show that spontaneous waves occur between embryonic day 18 (E18) and postnatal day 12 (P12), and that during that period they undergo major changes in transmitter dependence and propagation patterns. At early stages, spontaneous waves are largely GABA dependent and are mostly confined to the septum and ventral cortex. As development proceeds, wave initiation depends increasingly on AMPA-type glutamate receptors, and an ever increasing fraction of waves propagate into the dorsal cortex. The initiation sites and restricted propagation of waves at early stages are highly correlated with the position of GABAergic neurons in the cortex. The later switch to a glutamate-based mechanism allows propagation of waves into the dorsal cortex, and appears to be a compensatory mechanism that ensures continued wave generation even as GABA transmission becomes inhibitory.

  12. Flowable composite resins: do they decrease microleakage and shrinkage stress?

    PubMed

    Conte, Nicholas R; Goodchild, Jason H

    2013-06-01

    All flowable composites shrink and undergo polymerization stress; however, new technologic developments have sought to minimize this, while streamlining dental techniques and producing better results. The new category of bulk-fill flowable composites promotes the effective use of 4-mm increments while decreasing shrinkage stresses generated during polymerization.

  13. Current direction specificity of continuous θ-burst stimulation in modulating human motor cortex excitability when applied to somatosensory cortex.

    PubMed

    Jacobs, Mark F; Zapallow, Christopher M; Tsang, Philemon; Lee, Kevin G H; Asmussen, Michael J; Nelson, Aimee J

    2012-11-14

    The present study examines the influence of primary somatosensory cortex (SI) on corticospinal excitability within primary motor cortex (M1) using repetitive transcranial magnetic stimulation. Two groups of subjects participated and both received continuous theta-burst stimulation (cTBS) over SI. One group received cTBS oriented to induce anterior-to-posterior (AP) followed by posterior-to-anterior (PA) current flow in the cortex and the other group received cTBS in the opposite direction (PA-AP). Motor evoked potentials (MEPs) were measured from the first dorsal interosseous muscle of the left and right hand before and at three time points (5, 25, 45 min) following cTBS over left-hemisphere SI. CTBS over SI in the AP-PA direction increased contralateral MEPs at 5 and 45 min with a near significant increase at 25 min. In contrast, PA-AP cTBS decreased contralateral MEPs at 25 min. We conclude that cTBS over SI modulates neural output directed to the hand with effects that depend on the direction of induced current.

  14. Secretory function of adrenal cortex in chronic alcoholis.

    PubMed

    Feher, I

    1999-01-01

    Three groups of male subjects (healthy subjects, chronic alcoholics with liver cirrhosis and patients with acute viral hepatitis) were included in a 24 hour pattern of excretion of the total and some fractions of 17-ketosteroids (KS), basal concentration of 11-hydroxycorticosteroids (11-OHCS) and dehydroepiandrosterone (DHEA) in plasma, as well as changes of concentration of the same steroids in plasma 15, 30 and 60 minutes after a single i.m. injection of insulin. In regard to healthy subjects and patients with acute viral hepatitis, chronic alcoholics with liver cirrhosis excrete decreased quantities of total and some fractions of 17-KS. In regard to healthy subjects, decreased excretion of the sum androsterone and etiocholanole was established as well as increased DHEA secretion in patients with acute viral hepatitis. In chronic alcoholics with liver cirrhosis basal concentrations of 11-OHCS in plasma and their increase after insulin administration are the same as in healthy subjects, but values of DHEA concentrations in plasma are decreased. It has been pointed to the possibility of damages of the secretory function of adrenal cortex in chronic alcoholics with liver cirrhosis. On the basis of above mentioned results, there is an assumption that adrenal gland primarily provides normal secretion of C21 steroid and thus, satisfying needs for these steroids, increases secretion of DHEA. Follow up of DHEA urinary secretion may provide insight into basal activity of adrenal cortex, whereas the functional state of the liver must be taken into account when interpreting the results.

  15. [Analysis of cadmium in Cortex Ilicis Rotundae].

    PubMed

    Yan, Xiao-Hong; Hou, Hui-Chan; Zhang, Li-Wen; Wang, Zi

    2012-04-01

    To study the contents of cadmium in Cortex Ilicis Rotundae and provide evidence for establishing the detection limit of cadmium in its quality standard. ICP-MS was used to determine the contents of cadmium in 18 batches of Ilex L. The contents of cadmium in 10 batches of Cortex Ilex Rotunda ranged from 3.4 to 10.4 mg/kg,and the contents of cadmium in Ilex asprella and Ilex pubescents were more than 0.3 mg/kg. The contents of cadmium of Cortex Ilicis Rotundae, Ilex asprella and Ilex pubescents have particular characterise, and this study provides a basic for the analysis of cadmium in Cortex Ilicis Rotundace and other plants of this genus.

  16. Somatosensory responses in a human motor cortex

    PubMed Central

    Donoghue, John P.; Hochberg, Leigh R.

    2013-01-01

    Somatic sensory signals provide a major source of feedback to motor cortex. Changes in somatosensory systems after stroke or injury could profoundly influence brain computer interfaces (BCI) being developed to create new output signals from motor cortex activity patterns. We had the unique opportunity to study the responses of hand/arm area neurons in primary motor cortex to passive joint manipulation in a person with a long-standing brain stem stroke but intact sensory pathways. Neurons responded to passive manipulation of the contralateral shoulder, elbow, or wrist as predicted from prior studies of intact primates. Thus fundamental properties and organization were preserved despite arm/hand paralysis and damage to cortical outputs. The same neurons were engaged by attempted arm actions. These results indicate that intact sensory pathways retain the potential to influence primary motor cortex firing rates years after cortical outputs are interrupted and may contribute to online decoding of motor intentions for BCI applications. PMID:23343902

  17. A neurophysiological study of patients undergoing radical prostatectomy.

    PubMed

    Hansen, M V; Ertekin, C; Larsson, L E; Pedersen, K

    1989-01-01

    24 men suffering from localized prostatic cancer undergoing radical retropubic nerve-sparing prostatectomy were investigated by the following electrophysiological methods: Bulbocavernosus reflexes elicited from the penile skin or the posterior urethra, sensory thresholds in the posterior urethra, cerebral evoked potentials after stimulation of the pudendal nerve or the posterior urethra. 15 men were examined 4-33 months postoperatively only, 5 men were examined only preoperatively and 4 men were examined both pre- and postoperatively. 10 men suffering from minor problems due to benign prostatic hyperplasia served as controls. In patients with localized cancer of the prostate, the findings did not differ from those in the control group. In the operated group the findings were pathological in a large proportion of the patients, indicating injuries both to nervous pathways running through the pelvic nerve plexus and in the pudendal nerve. The conclusions were: Localized cancer of the prostate has minimal or no risk at all of impaired functioning in the pelvic nervous pathways. Radical retropubic prostatectomy may in some cases be undertaken without any objective evidence of injury to these nervous pathways, but is often followed by findings indicating such injury. The dorsal nerve of the penis may be affected by the operation. Transcranial stimulation of the motor cortex is a useful method in the evaluation of prolonged or absent bulbocavernosus reflexes.

  18. Developmental changes in mental arithmetic: evidence for increased functional specialization in the left inferior parietal cortex.

    PubMed

    Rivera, S M; Reiss, A L; Eckert, M A; Menon, V

    2005-11-01

    Arithmetic reasoning is arguably one of the most important cognitive skills a child must master. Here we examine neurodevelopmental changes in mental arithmetic. Subjects (ages 8-19 years) viewed arithmetic equations and were asked to judge whether the results were correct or incorrect. During two-operand addition or subtraction trials, for which accuracy was comparable across age, older subjects showed greater activation in the left parietal cortex, along the supramarginal gyrus and adjoining anterior intra-parietal sulcus as well as the left lateral occipital temporal cortex. These age-related changes were not associated with alterations in gray matter density, and provide novel evidence for increased functional maturation with age. By contrast, younger subjects showed greater activation in the prefrontal cortex, including the dorsolateral and ventrolateral prefrontal cortex and the anterior cingulate cortex, suggesting that they require comparatively more working memory and attentional resources to achieve similar levels of mental arithmetic performance. Younger subjects also showed greater activation of the hippocampus and dorsal basal ganglia, reflecting the greater demands placed on both declarative and procedural memory systems. Our findings provide evidence for a process of increased functional specialization of the left inferior parietal cortex in mental arithmetic, a process that is accompanied by decreased dependence on memory and attentional resources with development.

  19. Cognitive control and the anterior cingulate cortex: how conflicting stimuli affect attentional control in the rat

    PubMed Central

    Newman, Lori A.; Creer, David J.; McGaughy, Jill A.

    2014-01-01

    Converging evidence supports the hypothesis that the prefrontal cortex is critical for cognitive control. One prefrontal subregion, the anterior cingulate cortex, is hypothesized to be necessary to resolve response conflicts, disregard salient distractors and alter behavior in response to the generation of an error. These situations all involve goal-oriented monitoring of performance in order to effectively adjust cognitive processes. Several neuropsychological disorders, e.g., schizophrenia, attention deficit hyperactivity and obsessive compulsive disorder, are accompanied by morphological changes in the anterior cingulate cortex. These changes are hypothesized to underlie the impairments on tasks that require cognitive control found in these subjects. A novel conflict monitoring task was used to assess the effects on cognitive control of excitotoxic lesions to anterior cingulate cortex in rats. Prior to surgery all subjects showed improved accuracy on the second of two consecutive, incongruent trials. Lesions to the anterior cingulate cortex abolished this. Lesioned animals had difficulty in adjusting cognitive control on a trial-by-trial basis regardless of whether cognitive changes were increased or decreased. These results support a role for the anterior cingulate cortex in adjustments in cognitive control. PMID:25051488

  20. Effect of cadmium exposure on the histopathology of cerebral cortex in juvenile mice.

    PubMed

    Yang, X F; Fan, G Y; Liu, D Y; Zhang, H T; Xu, Z Y; Ge, Y M; Wang, Z L

    2015-06-01

    Cadmium, a heavy metal, is a toxic environmental and industrial pollutant. Exposure to cadmium can lead to the toxic effects in a variety of tissues, also including the brain. The present study investigated the effect of cadmium exposure on the histopathology of cerebral cortex in juvenile mice. Juvenile mice were randomly divided into control, low (1.87 mg/kg), medium (3.74 mg/kg), and high (7.48 mg/kg) dose groups. After cadmium exposure by drinking water for 10 days, the cerebral cortex was obtained for histopathology studies. The medium and high dose of cadmium, rather than low dose, could induce the histopathology alterations of cerebral cortex in a dose-dependent manner. In the high-dose group, microstructure significantly showed pia mater encephali divorcing from cerebral cortex layer, serious hyperemia of blood capillary in pia mater encephali and cerebral cortex, broadening vessel peripheral clearance, a large number of eosinophil leukocyte infiltrating around blood vessel, vacuolar degeneration in part granule cells, and obviously increasing apoptotic cells. Ultrastructure obviously displayed marginalized heterochromatin, incomplete or fused nuclear membranes, broadened perinuclear space, ambiguous mitochondria cristae, decreased synaptic cleft, and fused presynaptic and postsynaptic membrane. Our results revealed that cadmium at the middle and high dose could induce obvious microstructure and ultrastructure alterations of cerebral cortex in juvenile mice, which may be one important mechanism of cadmium neurotoxicity.

  1. Perirhinal Cortex Lesions in Rats: Novelty Detection and Sensitivity to Interference

    PubMed Central

    2015-01-01

    Rats with perirhinal cortex lesions received multiple object recognition trials within a continuous session to examine whether they show false memories. Experiment 1 focused on exploration patterns during the first object recognition test postsurgery, in which each trial contained 1 novel and 1 familiar object. The perirhinal cortex lesions reduced time spent exploring novel objects, but did not affect overall time spent exploring the test objects (novel plus familiar). Replications with subsequent cohorts of rats (Experiments 2, 3, 4.1) repeated this pattern of results. When all recognition memory data were combined (Experiments 1–4), giving totals of 44 perirhinal lesion rats and 40 surgical sham controls, the perirhinal cortex lesions caused a marginal reduction in total exploration time. That decrease in time with novel objects was often compensated by increased exploration of familiar objects. Experiment 4 also assessed the impact of proactive interference on recognition memory. Evidence emerged that prior object experience could additionally impair recognition performance in rats with perirhinal cortex lesions. Experiment 5 examined exploration levels when rats were just given pairs of novel objects to explore. Despite their perirhinal cortex lesions, exploration levels were comparable with those of control rats. While the results of Experiment 4 support the notion that perirhinal lesions can increase sensitivity to proactive interference, the overall findings question whether rats lacking a perirhinal cortex typically behave as if novel objects are familiar, that is, show false recognition. Rather, the rats retain a signal of novelty but struggle to discriminate the identity of that signal. PMID:26030425

  2. Food related processes in the insular cortex

    PubMed Central

    Frank, Sabine; Kullmann, Stephanie; Veit, Ralf

    2013-01-01

    The insular cortex is a multimodal brain region with regional cytoarchitectonic differences indicating various functional specializations. As a multisensory neural node, the insular cortex integrates perception, emotion, interoceptive awareness, cognition, and gustation. Regarding the latter, predominantly the anterior part of the insular cortex is regarded as the primary taste cortex. In this review, we will specifically focus on the involvement of the insula in food processing and on multimodal integration of food-related items. Influencing factors of insular activation elicited by various foods range from calorie-content to the internal physiologic state, body mass index or eating behavior. Sensory perception of food-related stimuli including seeing, smelling, and tasting elicits increased activation in the anterior and mid-dorsal part of the insular cortex. Apart from the pure sensory gustatory processing, there is also a strong association with the rewarding/hedonic aspects of food items, which is reflected in higher insular activity and stronger connections to other reward-related areas. Interestingly, the processing of food items has been found to elicit different insular activation in lean compared to obese subjects and in patients suffering from an eating disorder (anorexia nervosa (AN), bulimia nervosa (BN)). The knowledge of functional differences in the insular cortex opens up the opportunity for possible noninvasive treatment approaches for obesity and eating disorders. To target brain functions directly, real-time functional magnetic resonance imaging neurofeedback offers a state-of-the-art tool to learn to control the anterior insular cortex activity voluntarily. First evidence indicates that obese adults have an enhanced ability to regulate the anterior insular cortex. PMID:23986683

  3. 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

  4. Category-Selectivity in Human Visual Cortex Follows Cortical Topology: A Grouped icEEG Study

    PubMed Central

    Conner, Christopher Richard; Whaley, Meagan Lee; Baboyan, Vatche George; Tandon, Nitin

    2016-01-01

    Neuroimaging studies suggest that category-selective regions in higher-order visual cortex are topologically organized around specific anatomical landmarks: the mid-fusiform sulcus (MFS) in the ventral temporal cortex (VTC) and lateral occipital sulcus (LOS) in the lateral occipital cortex (LOC). To derive precise structure-function maps from direct neural signals, we collected intracranial EEG (icEEG) recordings in a large human cohort (n = 26) undergoing implantation of subdural electrodes. A surface-based approach to grouped icEEG analysis was used to overcome challenges from sparse electrode coverage within subjects and variable cortical anatomy across subjects. The topology of category-selectivity in bilateral VTC and LOC was assessed for five classes of visual stimuli—faces, animate non-face (animals/body-parts), places, tools, and words—using correlational and linear mixed effects analyses. In the LOC, selectivity for living (faces and animate non-face) and non-living (places and tools) classes was arranged in a ventral-to-dorsal axis along the LOS. In the VTC, selectivity for living and non-living stimuli was arranged in a latero-medial axis along the MFS. Written word-selectivity was reliably localized to the intersection of the left MFS and the occipito-temporal sulcus. These findings provide direct electrophysiological evidence for topological information structuring of functional representations within higher-order visual cortex. PMID:27272936

  5. Temporal envelope of time-compressed speech represented in the human auditory cortex

    PubMed Central

    Nourski, Kirill V.; Reale, Richard A.; Oya, Hiroyuki; Kawasaki, Hiroto; Kovach, Christopher K.; Chen, Haiming; Howard, Matthew A.; Brugge, John F.

    2010-01-01

    Speech comprehension relies on temporal cues contained in the speech envelope, and the auditory cortex has been implicated as playing a critical role in encoding this temporal information. We investigated auditory cortical responses to speech stimuli in subjects undergoing invasive electrophysiological monitoring for pharmacologically refractory epilepsy. Recordings were made from multi-contact electrodes implanted in Heschl’s gyrus (HG). Speech sentences, time-compressed from 0.75 to 0.20 of natural speaking rate, elicited average evoked potentials (AEPs) and increases in event-related band power (ERBP) of cortical high frequency (70–250 Hz) activity. Cortex of posteromedial HG, the presumed core of human auditory cortex, represented the envelope of speech stimuli in the AEP and ERBP. Envelope-following in ERBP, but not in AEP, was evident in both language dominant and non-dominant hemispheres for relatively high degrees of compression where speech was not comprehensible. Compared to posteromedial HG, responses from anterolateral HG — an auditory belt field — exhibited longer latencies, lower amplitudes and little or no time locking to the speech envelope. The ability of the core auditory cortex to follow the temporal speech envelope over a wide range of speaking rates leads us to conclude that such capacity in itself is not a limiting factor for speech comprehension. PMID:20007480

  6. Neural dissociations in attitude strength: Distinct regions of cingulate cortex track ambivalence and certainty.

    PubMed

    Luttrell, Andrew; Stillman, Paul E; Hasinski, Adam E; Cunningham, William A

    2016-04-01

    People's behaviors are often guided by valenced responses to objects in the environment. Beyond positive and negative evaluations, attitudes research has documented the importance of attitude strength--qualities of an attitude that enhance or attenuate its impact and durability. Although neuroscience research has extensively investigated valence, little work exists on other related variables like metacognitive judgments about one's attitudes. It remains unclear, then, whether the various indicators of attitude strength represent a single underlying neural process or whether they reflect independent processes. To examine this, we used functional MRI (fMRI) to identify the neural correlates of attitude strength. Specifically, we focus on ambivalence and certainty, which represent metacognitive judgments that people can make about their evaluations. Although often correlated, prior neuroscience research suggests that these 2 attributes may have distinct neural underpinnings. We investigate this by having participants make evaluative judgments of visually presented words while undergoing fMRI. After scanning, participants rated the degree of ambivalence and certainty they felt regarding their attitudes toward each word. We found that these 2 judgments corresponded to distinct brain regions' activity during the process of evaluation. Ambivalence corresponded to activation in anterior cingulate cortex, dorsomedial prefrontal cortex, and posterior cingulate cortex. Certainty, however, corresponded to activation in unique areas of the precuneus/posterior cingulate cortex. These results support a model treating ambivalence and certainty as distinct, though related, attitude strength variables, and we discuss implications for both attitudes and neuroscience research. (c) 2016 APA, all rights reserved).

  7. Premotor cortex mediates perceptual performance.

    PubMed

    Callan, Daniel; Callan, Akiko; Gamez, Mario; Sato, Masa-aki; Kawato, Mitsuo

    2010-06-01

    Articulatory goals have long been proposed to mediate perception. Examples include direct realist and constructivist (analysis by synthesis) theories of speech perception. Although the activity in brain regions involved with action production has been shown to be present during action observation (Mirror Neuron System), the relationship of this activity to perceptual performance has not been clearly demonstrated at the event level. To this end we used functional magnetic resonance imaging fMRI and magnetoencephalography MEG to measure brain activity for correct and incorrect trials of an auditory phonetic identification in noise task. FMRI analysis revealed activity in the premotor cortex including the neighboring frontal opercular part of Broca's area (PMC/Broca's) for both perception and production tasks involving the same phonetic stimuli (potential mirror system site) that was significantly greater for correct over incorrect perceptual identification trials. Time-frequency analysis of single trials conducted over MEG current localized to PMC/Broca's using a hierarchical variational Bayesian source analysis technique revealed significantly greater event-related synchronization ERS and desynchronization ERD for correct over incorrect trials in the alpha, beta, and gamma frequency range prior to and after stimulus presentation. Together, these fMRI and MEG results are consistent with the hypothesis that articulatory processes serve to facilitate perceptual performance, while further dispelling concerns that activity found in ventral PMC/Broca's (mirror system) is merely a product of covert production of the perceived action. The finding of performance predictive activity prior to stimulus onset as well as activity related to task difficulty instead of information available in stimulation are consistent with constructivist and contrary to direct realist theories of perception.

  8. The Role of Human Parietal Cortex in Attention Networks

    ERIC Educational Resources Information Center

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

    2004-01-01

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

  9. The Role of Human Parietal Cortex in Attention Networks

    ERIC Educational Resources Information Center

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

    2004-01-01

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

  10. Status of selected nutrients in obese dogs undergoing caloric restriction

    PubMed Central

    2013-01-01

    Background The purpose of this study was to test the hypothesis that dog plasma concentrations of selected nutrients decrease after undergoing caloric restriction for weight loss. Thirty-one overweight dogs that had successfully lost at least 15% of initial body weight were included in the study. Nutrients that had been previously identified to be at potential risk of deficiency during caloric restriction were measured in plasma (choline, amino acids) and urine (selenium) at the initiation and completion of a standardized weight loss regimen in dogs. Results Dogs remained healthy throughout the study, and no signs attributable to nutrient deficiency were noted. Percentage weight loss was 28.3% (16.0-40.1%) starting body weight, over a period of 250 days (91–674 days). Median energy intake during the weight loss period was 62 (44 to 74) Kcal/kg0.75 target weight per day. Choline (P = 0.046) and threonine (P = 0.02) decreased after weight loss. Glycine (P = 0.041), and urinary selenium:creatinine ratio (P = 0.006) both increased after weight loss. There were no other significant differences in plasma nutrient concentrations. Conclusions Since concentrations of most measured nutrients did not change significantly, the data are not consistent with widespread nutrient deficiency in dogs undergoing caloric restriction using a diet formulated for weight loss. However, the significance of the decrease in plasma choline concentration requires further assessment. PMID:24156605

  11. Neurokinin-1 receptors are decreased in major depressive disorder.

    PubMed

    Stockmeier, Craig A; Shi, Xiaochun; Konick, Lisa; Overholser, James C; Jurjus, George; Meltzer, Herbert Y; Friedman, Lee; Blier, Pierre; Rajkowska, Grazyna

    2002-07-02

    Treatment with an antagonist at the neurokinin-1 (NK-1) receptor may alleviate depression, however the brain region(s) in which the NK-1 receptor antagonist exerts its therapeutic effect is unknown. [125I]BH-Substance P was used to measure NK-1 receptors postmortem in cytoarchitectonically defined areas of rostral orbitofrontal cortex (Brodmann's area 47) of subjects with major depressive disorder (n = 12, six females) and psychiatrically normal subjects (n = 11, five females). Six subjects with depression died by suicide. Subjects with depression showed decreased binding to NK-1 receptors across all cortical layers (p = 0.024). The pathophysiology of depression, and the reported therapeutic benefit of NK-1 receptor antagonists, may thus involve NK-1 receptors in prefrontal cortex.

  12. Retrieval is not necessary to trigger reconsolidation of object recognition memory in the perirhinal cortex

    PubMed Central

    Santoyo-Zedillo, Marianela; Rodriguez-Ortiz, Carlos J.; Chavez-Marchetta, Gianfranco; Bermudez-Rattoni, Federico

    2014-01-01

    Memory retrieval has been considered as requisite to initiate memory reconsolidation; however, some studies indicate that blocking retrieval does not prevent memory from undergoing reconsolidation. Since N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors in the perirhinal cortex have been involved in object recognition memory formation, the present study evaluated whether retrieval and reconsolidation are independent processes by manipulating these glutamate receptors. The results showed that AMPA receptor antagonist infusions in the perirhinal cortex blocked retrieval, but did not affect memory reconsolidation, although NMDA receptor antagonist infusions disrupted reconsolidation even if retrieval was blocked. Importantly, neither of these antagonists disrupted short-term memory. These data suggest that memory underwent reconsolidation even in the absence of retrieval. PMID:25128536

  13. Nutritional status of patients undergoing chemoradiotherapy for lung cancer.

    PubMed

    Shintani, Yasushi; Ikeda, Naoki; Matsumoto, Tomoshige; Kadota, Yoshihisa; Okumura, Meinoshin; Ohno, Yuko; Ohta, Mitsunori

    2012-04-01

    Impaired nutrition is an important predictor of perioperative complications in lung cancer patients, and preoperative chemoradiotherapy increases the risk of such complications. The goal of this study was to assess the effect of an immune-enhancing diet on nutritional status in patients undergoing lung resection after chemoradiotherapy. We compared the preoperative nutritional status in 15 patients with lung cancer undergoing lung resection without chemoradiotherapy and 15 who had chemoradiotherapy. Body mass index and lymphocyte counts were lower in patients who had chemoradiotherapy. Although there was no difference in the rate of postoperative morbidity between groups, the chemoradiotherapy patients were more likely to have severe complications postoperatively. After chemoradiotherapy in 12 patients, 6 received oral Impact for 5 days, and 6 had a conventional diet before surgery. Oral intake of Impact for 5 days before surgery modified the decrease in transferrin and lymphocytes after the operation. Preoperative immunonutrition may improve the perioperative nutritional status after induction chemoradiotherapy in patients undergoing lung cancer surgery, and reduce the severity of postoperative complications. These potential benefits need to be confirmed in a randomized controlled trial.

  14. Effects of Visual Cortex Activation on the Nociceptive Blink Reflex in Healthy Subjects

    PubMed Central

    Sava, Simona L.; de Pasqua, Victor; Magis, Delphine; Schoenen, Jean

    2014-01-01

    Bright light can cause excessive visual discomfort, referred to as photophobia. The precise mechanisms linking luminance to the trigeminal nociceptive system supposed to mediate this discomfort are not known. To address this issue in healthy human subjects we modulated differentially visual cortex activity by repetitive transcranial magnetic stimulation (rTMS) or flash light stimulation, and studied the effect on supraorbital pain thresholds and the nociceptive-specific blink reflex (nBR). Low frequency rTMS that inhibits the underlying cortex, significantly decreased pain thresholds, increased the 1st nBR block ipsi- and contralaterally and potentiated habituation contralaterally. After high frequency or sham rTMS over the visual cortex, and rMS over the right greater occipital nerve we found no significant change. By contrast, excitatory flash light stimulation increased pain thresholds, decreased the 1st nBR block of ipsi- and contralaterally and increased habituation contralaterally. Our data demonstrate in healthy subjects a functional relation between the visual cortex and the trigeminal nociceptive system, as assessed by the nociceptive blink reflex. The results argue in favour of a top-down inhibitory pathway from the visual areas to trigemino-cervical nociceptors. We postulate that in normal conditions this visuo-trigeminal inhibitory pathway may avoid disturbance of vision by too frequent blinking and that hypoactivity of the visual cortex for pathological reasons may promote headache and photophobia. PMID:24936654

  15. Optical properties of the medulla and the cortex of human scalp hair

    NASA Astrophysics Data System (ADS)

    Kharin, Aleksey; Varghese, Babu; Verhagen, Rieko; Uzunbajakava, Natallia

    2009-03-01

    An increasing number of applications, including non- or minimally invasive diagnostics and treatment as well as various cosmetic procedures, has resulted in a need to determine the optical properties of hair and its structures. We report on the measurement of the total attenuation coefficient of the cortex and the medulla of blond, gray, and Asian black human scalp hair at a 633-nm wavelength. Our results show that for blond and gray hair the total attenuation coefficient of the medulla is more than 200 times higher compared to that of the cortex. This difference is only 1.5 times for Asian black hair. Furthermore, we present the total attenuation coefficient of the cortex of blond, gray, light brown, and Asian black hair measured at wavelengths of 409, 532, 633, 800, and 1064 nm. The total attenuation coefficient consistently decreases with an increase in wavelength, as well as with a decrease in hair pigmentation. Additionally, we demonstrate the dependence of the total attenuation coefficient of the cortex and the medulla of Asian black hair on the polarization of incident light. A similar dependence is observed for the cortex of blond and gray hair but not for the medulla of these hair types.

  16. Binding crossmodal object features in perirhinal cortex.

    PubMed

    Taylor, Kirsten I; Moss, Helen E; Stamatakis, Emmanuel A; Tyler, Lorraine K

    2006-05-23

    Knowledge of objects in the world is stored in our brains as rich, multimodal representations. Because the neural pathways that process this diverse sensory information are largely anatomically distinct, a fundamental challenge to cognitive neuroscience is to explain how the brain binds the different sensory features that comprise an object to form meaningful, multimodal object representations. Studies with nonhuman primates suggest that a structure at the culmination of the object recognition system (the perirhinal cortex) performs this critical function. In contrast, human neuroimaging studies implicate the posterior superior temporal sulcus (pSTS). The results of the functional MRI study reported here resolve this apparent discrepancy by demonstrating that both pSTS and the perirhinal cortex contribute to crossmodal binding in humans, but in different ways. Significantly, only perirhinal cortex activity is modulated by meaning variables (e.g., semantic congruency and semantic category), suggesting that these two regions play complementary functional roles, with pSTS acting as a presemantic, heteromodal region for crossmodal perceptual features, and perirhinal cortex integrating these features into higher-level conceptual representations. This interpretation is supported by the results of our behavioral study: Patients with lesions, including the perirhinal cortex, but not patients with damage restricted to frontal cortex, were impaired on the same crossmodal integration task, and their performance was significantly influenced by the same semantic factors, mirroring the functional MRI findings. These results integrate nonhuman and human primate research by providing converging evidence that human perirhinal cortex is also critically involved in processing meaningful aspects of multimodal object representations.

  17. Perirhinal cortex and temporal lobe epilepsy.

    PubMed

    Biagini, Giuseppe; D'Antuono, Margherita; Benini, Ruba; de Guzman, Philip; Longo, Daniela; Avoli, Massimo

    2013-08-29

    The perirhinal cortex-which is interconnected with several limbic structures and is intimately involved in learning and memory-plays major roles in pathological processes such as the kindling phenomenon of epileptogenesis and the spread of limbic seizures. Both features may be relevant to the pathophysiology of mesial temporal lobe epilepsy that represents the most refractory adult form of epilepsy with up to 30% of patients not achieving adequate seizure control. Compared to other limbic structures such as the hippocampus or the entorhinal cortex, the perirhinal area remains understudied and, in particular, detailed information on its dysfunctional characteristics remains scarce; this lack of information may be due to the fact that the perirhinal cortex is not grossly damaged in mesial temporal lobe epilepsy and in models mimicking this epileptic disorder. However, we have recently identified in pilocarpine-treated epileptic rats the presence of selective losses of interneuron subtypes along with increased synaptic excitability. In this review we: (i) highlight the fundamental electrophysiological properties of perirhinal cortex neurons; (ii) briefly stress the mechanisms underlying epileptiform synchronization in perirhinal cortex networks following epileptogenic pharmacological manipulations; and (iii) focus on the changes in neuronal excitability and cytoarchitecture of the perirhinal cortex occurring in the pilocarpine model of mesial temporal lobe epilepsy. Overall, these data indicate that perirhinal cortex networks are hyperexcitable in an animal model of temporal lobe epilepsy, and that this condition is associated with a selective cellular damage that is characterized by an age-dependent sensitivity of interneurons to precipitating injuries, such as status epilepticus.

  18. Prefrontal Cortex Cognitive Deficits in Children Treated Early and Continuously for PKU.

    ERIC Educational Resources Information Center

    Diamond, Adele; Prevor, Meredith B.; Druin, Donald P.; Callender, Glenda

    1997-01-01

    Hypothesized that elevated ratio of phenylalanine to tyrosine in blood of children with phenylketonuria uniquely affects cognitive functions dependent on prefrontal cortex because of the special sensitivity of prefrontally projecting dopamine neurons to small decreases in tyrosine. Found that children whose phenylalanine levels were three to five…

  19. Prefrontal Cortex Cognitive Deficits in Children Treated Early and Continuously for PKU.

    ERIC Educational Resources Information Center

    Diamond, Adele; Prevor, Meredith B.; Druin, Donald P.; Callender, Glenda

    1997-01-01

    Hypothesized that elevated ratio of phenylalanine to tyrosine in blood of children with phenylketonuria uniquely affects cognitive functions dependent on prefrontal cortex because of the special sensitivity of prefrontally projecting dopamine neurons to small decreases in tyrosine. Found that children whose phenylalanine levels were three to five…

  20. [The acceleration of ultrastructure changes of synapses in somatosensory cortex of the rats at repeated simulation of weightlessness effects].

    PubMed

    Krasnov, I B; D'iachkova, L N

    2006-01-01

    The electronmicroscopica/study of brain somatosensory cortex in the rats, exposed to postponed for a long time repeated lack of support load on hindlimbs by means of tail-suspension, has been revealed in hindlimb area of cortex the changes of ultrastructure of axodendritic synapses and neurons pointing out the acceleration of decrease in functional activity of synapses and neurons in 3-4 layers at postponed for a long time repeated simulation of weightlessness effects.

  1. The ventral pallidum and orbitofrontal cortex support food pleasantness inferences

    PubMed Central

    Simmons, W. Kyle; Rapuano, Kristina M.; Ingeholm, John E.; Avery, Jason; Kallman, Seth; Hall, Kevin D.; Martin, Alex

    2013-01-01

    Food advertisements often promote choices that are driven by inferences about the hedonic pleasures of eating a particular food. Given the individual and public health consequences of obesity, it is critical to address unanswered questions about the specific neural systems underlying these hedonic inferences. For example, although regions such as the orbitofrontal cortex (OFC) are frequently observed to respond more to pleasant food images than less hedonically pleasing stimuli, one important hedonic brain region in particular has largely remained conspicuously absent among human studies of hedonic response to food images. Based on rodent research demonstrating that activity in the ventral pallidum underlies the hedonic pleasures experienced upon eating food rewards, one might expect that activity in this important ‘hedonic hotspot’ might also track inferred food pleasantness. To date, however, no human studies have assessed this question. We thus asked human subjects to undergo fMRI and make item-by-item ratings of how pleasant it would be to eat particular visually perceived foods. Activity in the ventral pallidum was strongly modulated with pleasantness inferences. Additionally, activity within a region of the orbitofrontal cortex that tracks the pleasantness of tastes was also modulated with inferred pleasantness. Importantly, the reliability of these findings is demonstrated by their replication when we repeated the experiment at a new site with new subjects. These two experiments demonstrate that the ventral pallidum, in addition to the OFC, plays a central role in the moment-to-moment hedonic inferences that influence food-related decision-making. PMID:23397317

  2. Surface Vulnerability of Cerebral Cortex to Major Depressive Disorder

    PubMed Central

    Li, Gang; Fralick, Drew; Shen, Ting; Qiu, Meihui; Liu, Jun; Jiang, Kaida; Shen, Dinggang; Fang, Yiru

    2015-01-01

    Major depressive disorder (MDD) is accompanied by atypical brain structure. This study first presents the alterations in the cortical surface of patients with MDD using multidimensional structural patterns that reflect different neurodevelopment. Sixteen first-episode, untreated patients with MDD and 16 matched healthy controls underwent a magnetic resonance imaging (MRI) scan. The cortical maps of thickness, surface area, and gyrification were examined using the surface-based morphometry (SBM) approach. Increase of cortical thickness was observed in the right posterior cingulate region and the parietal cortex involving the bilateral inferior, left superior parietal and right paracentral regions, while decreased thickness was noted in the parietal cortex including bilateral pars opercularis and left precentral region, as well as the left rostral-middle frontal regions in patients with MDD. Likewise, increased or decreased surface area was found in five sub-regions of the cingulate gyrus, parietal and frontal cortices (e.g., bilateral inferior parietal and superior frontal regions). In addition, MDD patients exhibited a significant hypergyrification in the right precentral and supramarginal region. This integrated structural assessment of cortical surface suggests that MDD patients have cortical alterations of the frontal, parietal and cingulate regions, indicating a vulnerability to MDD during earlier neurodevelopmental process. PMID:25793287

  3. Autonomic and prefrontal cortex responses to autobiographical recall of emotions.

    PubMed

    Marci, Carl D; Glick, Debra M; Loh, Rebecca; Dougherty, Darin D

    2007-09-01

    The present study combined measures of regional cerebral blood flow (rCBF) using positron emission tomography (PET) with measures of the autonomic nervous system using skin conductance (SC), heart rate (HR), and the high frequency band of heart rate variability (HRV) in ten healthy participants who were exposed to autobiographical scripts of memories for three target emotions: anger, happiness, and sadness. According to the results, anger was the only emotion to show a significant increase in sympathetic activity, accompanied by a significant decrease in HRV when compared with a neutral script. Anger was also the only emotion to show significant changes in rCBF in the prefrontal cortex. By contrast, the results for the happy and sad conditions showed no significant increase in sympathetic activity and no changes in rCBF in the prefrontal cortex in comparison with the neutral script. The findings suggest that a relative increase in sympathetic activity with a reciprocal decrease in parasympathetic activity may be necessary to generate frontal activity in autobiographical recall of emotions.

  4. Acute effects of alcohol on unit activity in the motor cortex of freely moving rabbits: comparison with the limbic cortex.

    PubMed

    Alexandrov, Y I; Grinchenko, Y V; Laukka, S; Järvilehto, T; Maz, V N

    1991-07-01

    Unit activity was recorded from the motor cortex of eight freely moving rabbits in order to examine the acute effect of ethanol (1 g kg-1) on organization of unit activity and to compare it with our earlier results from the limbic cortex. The rabbits performed a food-acquisition task in the experimental cage. Unit activity was recorded during behaviour in the control experiment followed by the alcohol experiment on the next day. After ethanol, behavioural mistakes and the duration of the behavioural cycle significantly increased. In the control experiments activation of 58% of the units had no constant relation to the phases of the behavioural cycle (non-involved units), whereas 42% of the units were constantly activated during certain phases (involved units). Two per cent of the latter units were activated in relation to newly learned behavioural acts (e.g. pedal pressing; L units), 28% in relation to food seizure and/or grinding (S units) and 12% in relation to certain movements during different behavioural acts (M units). Ethanol had no effect on the number of active units and the same relation between the number of non-involved and involved units or between the number of different types of involved units was found. However, the number of involved units decreased in the upper and increased in the lower cortical layers. Also the number of units with low background frequency increased, although the frequency within activations did not change. In our earlier study the number of active units in the limbic cortex decreased after ethanol by one third and the relation between the number of L and M units was reversed.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Declarative association in the perirhinal cortex.

    PubMed

    Naya, Yuji

    2016-12-01

    Declarative memories are our so-called daily language memories, which we are able to describe or explicitly experience through the act of remembering. This conscious recollection makes it possible for us to think about the future based on our previous experience (episodic memory) and knowledge (semantic memory). This cognitive function is substantiated by the medial temporal lobe (MTL), a hierarchically organized complex in which the perirhinal cortex and parahippocampal cortex provide item and context information to the hippocampus via the entorhinal cortex, and the hippocampus plays the main role in association and recollection. This conventional view provides an easily understood structure to the declarative memory system. However, neurophysiological studies reporting the activities of single neurons bring a more complicated view. In this article, I review single-unit studies, particularly those focused on the perirhinal cortex and hippocampus, and suggest that association processes for declarative memory are more distributed over the MTL areas. The perirhinal cortex represents both between-domain associations (e.g., item-reward, item-place and item-time) and within-domain associations (e.g., item-item) and contributes to both subcategories of declarative memory (i.e., episodic and semantic memory) in a way that is complementary with the hippocampus. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  6. [Prefrontal cortex in memory and attention processes].

    PubMed

    Allegri, R F; Harris, P

    The role of the prefrontal cortex still remains poorly understood. Only after 1970, the functions of the frontal lobes have been conceptualized from different points of view (behaviorism, cognitivism). Recently,different parallel circuits connecting discrete cortical and subcortical regions of the frontal lobes have been described. Three of these circuits are the most relevant to understanding of behavior: the dorsolateral prefrontal circuit, that mediates executive behavior; the orbitofrontal prefrontal circuit, mediating social behavior, and the medial frontal circuit, involved in motivation. Damage to the frontal cortex impairs planning, problem solving, reasoning, concept formation, temporal ordering of stimuli, estimation, attention, memory search, maintaining information in working memory, associative learning,certain forms of skilled motor activities, image generation and manipulation of the spatial properties of a stimulus, metacognitive thinking, and social cognition. Several theories have been proposed to explain the functions of the prefrontal cortex. Currently,the most influential cognitive models are: the Norman and Shallice supervisory attentional system, involved in non-routine selection; the Baddeley working memory model with the central executive as a supervisory controlling system, in which impairment leads to a 'dysexecutive syndrome'; and the Grafman's model of managerial knowledge units, stored as macrostructured information in the frontal cortex. The prefrontal cortex is essential for attentional control, manipulation of stored knowledge and modulation of complex actions, cognition, emotion and behavior.

  7. Motor Cortex Neuroplasticity Following Brachial Plexus Transfer

    PubMed Central

    Dimou, Stefan; Biggs, Michael; Tonkin, Michael; Hickie, Ian B.; Lagopoulos, Jim

    2013-01-01

    In the past decade, research has demonstrated that cortical plasticity, once thought only to exist in the early stages of life, does indeed continue on into adulthood. Brain plasticity is now acknowledged as a core principle of brain function and describes the ability of the central nervous system to adapt and modify its structural organization and function as an adaptive response to functional demand. In this clinical case study we describe how we used neuroimaging techniques to observe the functional topographical expansion of a patch of cortex along the sensorimotor cortex of a 27-year-old woman following brachial plexus transfer surgery to re-innervate her left arm. We found bilateral activations present in the thalamus, caudate, insula as well as across the sensorimotor cortex during an elbow flex motor task. In contrast we found less activity in the sensorimotor cortex for a finger tap motor task in addition to activations lateralized to the left inferior frontal gyrus and thalamus and bilaterally for the insula. From a pain perspective the patient who had experienced extensive phantom limb pain (PLP) before surgery found these sensations were markedly reduced following transfer of the right brachial plexus to the intact left arm. Within the context of this clinical case the results suggest that functional improvements in limb mobility are associated with increased activation in the sensorimotor cortex as well as reduced PLP. PMID:23966938

  8. A Computational Model of Cerebral Cortex Folding

    PubMed Central

    Nie, Jingxin; Guo, Lei; Li, Gang; Faraco, Carlos; Miller, L Stephen; Liu, Tianming

    2010-01-01

    The geometric complexity and variability of the human cerebral cortex has long intrigued the scientific community. As a result, quantitative description of cortical folding patterns and the understanding of underlying folding mechanisms have emerged as important research goals. This paper presents a computational 3-dimensional geometric model of cerebral cortex folding initialized by MRI data of a human fetal brain and deformed under the governance of a partial differential equation modeling cortical growth. By applying different simulation parameters, our model is able to generate folding convolutions and shape dynamics of the cerebral cortex. The simulations of this 3D geometric model provide computational experimental support to the following hypotheses: 1) Mechanical constraints of the skull regulate the cortical folding process. 2) The cortical folding pattern is dependent on the global cell growth rate of the whole cortex. 3) The cortical folding pattern is dependent on relative rates of cell growth in different cortical areas. 4) The cortical folding pattern is dependent on the initial geometry of the cortex. PMID:20167224

  9. Dissociating motor cortex from the motor

    PubMed Central

    Schieber, Marc H

    2011-01-01

    Abstract During closed-loop control of a brain–computer interface, neurons in the primary motor cortex can be intensely active even though the subject may be making no detectable movement or muscle contraction. How can neural activity in the primary motor cortex become dissociated from the movements and muscles of the native limb that it normally controls? Here we examine circumstances in which motor cortex activity is known to dissociate from movement – including mental imagery, visuo-motor dissociation and instructed delay. Many such motor cortex neurons may be related to muscle activity only indirectly. Furthermore, the integration of thousands of synaptic inputs by individual α-motoneurons means that under certain circumstances even cortico-motoneuronal cells, which make monosynaptic connections to α-motoneurons, can become dissociated from muscle activity. The natural ability of motor cortex neurons under voluntarily control to become dissociated from bodily movement may underlie the utility of this cortical area for controlling brain–computer interfaces. PMID:22005673

  10. [Numerical taxonomy of corlor in Phellodendron Cortex].

    PubMed

    Jin, Yan; Huang, Lu-qi; Yuan, Yuan; Zhang, Shan-shan; Jin, Shi-yuan

    2015-10-01

    Through the investigation of Phellodendron Cortex on the market, and 28 batches of samples were collected. By using spectrophotometer the color values of outer surface, inner surface and cross - section of these samples were measured. These measured color data was translated into 3D structure diagram by using the Lab color space tool. The level difference value, the mean value and the threshold value were calculated based the measured color data of these different batches of samples. All 28 groups measured data was analyzed using the methods of Ward linkage and average Euclidean distance. At the same time, we invited Professor Jin Shiyuan, the "Chinese medicine master", to identify, quality-evaluate and grade these 28 batches of Phellodendron Cortex samples base on the traditional experience, then compared the traditional empirical results with the spectrophotometer measurement results. The result showed that, the Phellodendron Cortex could be divided into Phellodendri Amurensis Cortex and Phellodendri Chinensis Cortex by color numerical clustering, and classified according to quality. The classification result has a high degree of consistency with the traditional experience.

  11. Role of hypotension in decreasing cerebral blood flow in porcine endotoxemia

    SciTech Connect

    Miller, C.F.; Breslow, M.J.; Shapiro, R.M.; Traystman, R.J. )

    1987-10-01

    The role of reduced arterial blood pressure (MAP) in decreasing cerebral blood flow (CBF) during endotoxemia was studied in pentobarbital-anesthetized pigs. Microspheres were used to measure regional CBF changes during MAP manipulations in animals with and without endotoxin. Endotoxin decreased MAP to 50 mmHg and decreased blood flow to the cortex and cerebellum without affecting cerebral cortical oxygen consumption (CMRo{sub 2}). Elevating MAP from 50 to 70 mmHg during endotoxemia with norepinephrine did not change cortical blood flow or CMRo{sub 2} but increased cerebellar blood flow. Brain stem blood flow was not affected by endotoxin or norepinephrine. When MAP was decreased to 50 mmHg by hemorrhage without endotoxin, no change in blood flow to cortex, cerebellum, or brain stem was observed from base-line levels. These results suggest that decreased MAP below a lower limit for cerebral autoregulation does not account for the decreased CBF observed after endotoxin.

  12. Activations of muscarinic M1 receptors in the anterior cingulate cortex contribute to the antinociceptive effect via GABAergic transmission

    PubMed Central

    Matsuzaki, Yu; Honda, Kenji; Eto, Fumihiro; Furukawa, Tomonori; Migita, Keisuke; Irie, Keiichi; Mishima, Kenichi; Ueno, Shinya

    2017-01-01

    Background Cholinergic systems regulate the synaptic transmission resulting in the contribution of the nociceptive behaviors. Anterior cingulate cortex is a key cortical area to play roles in nociception and chronic pain. However, the effect of the activation of cholinergic system for nociception is still unknown in the cortical area. Here, we tested whether the activation of cholinergic receptors can regulate nociceptive behaviors in adult rat anterior cingulate cortex by integrative methods including behavior, immunohistochemical, and electrophysiological methods. Results We found that muscarinic M1 receptors were clearly expressed in the anterior cingulate cortex. Using behavioral tests, we identified that microinjection of a selective muscarinic M1 receptors agonist McN-A-343 into the anterior cingulate cortex dose dependently increased the mechanical threshold. In contrast, the local injection of McN-A-343 into the anterior cingulate cortex showed normal motor function. The microinjection of a selective M1 receptors antagonist pirenzepine blocked the McN-A-343-induced antinociceptive effect. Pirenzepine alone into the anterior cingulate cortex decreased the mechanical thresholds. The local injection of the GABAA receptors antagonist bicuculline into the anterior cingulate cortex also inhibited the McN-A-343-induced antinociceptive effect and decreased the mechanical threshold. Finally, we further tested whether the activation of M1 receptors could regulate GABAergic transmission using whole-cell patch-clamp recordings. The activation of M1 receptors enhanced the frequency of spontaneous and miniature inhibitory postsynaptic currents as well as the amplitude of spontaneous inhibitory postsynaptic currents in the anterior cingulate cortex. Conclusions These results suggest that the activation of muscarinic M1 receptors in part increased the mechanical threshold by increasing GABAergic transmitter release and facilitating GABAergic transmission in the anterior

  13. Remodeling the Dendritic Spines in the Hindlimb Representation of the Sensory Cortex after Spinal Cord Hemisection in Mice.

    PubMed

    Zhang, Kexue; Zhang, Jinhui; Zhou, Yanmei; Chen, Chao; Li, Wei; Ma, Lei; Zhang, Licheng; Zhao, Jingxin; Gan, Wenbiao; Zhang, Lihai; Tang, Peifu

    2015-01-01

    Spinal cord injury (SCI) can induce remodeling of multiple levels of the cerebral cortex system especially in the sensory cortex. The aim of this study was to assess, in vivo and bilaterally, the remodeling of dendritic spines in the hindlimb representation of the sensory cortex after spinal cord hemisection. Thy1-YFP transgenic mice were randomly divided into the control group and the SCI group, and the spinal vertebral plates (T11-T12) of all mice were excised. Next, the left hemisphere of the spinal cord (T12) was hemisected in the SCI group. The hindlimb representations of the sensory cortex in both groups were imaged bilaterally on the day before (0d), and three days (3d), two weeks (2w), and one month (1m) after the SCI. The rates of stable, newly formed, and eliminated spines were calculated by comparing images of individual dendritic spine in the same areas at different time points. In comparison to the control group, the rate of newly formed spines in the contralateral sensory cortex of the SCI group increased at three days and two weeks after injury. The rates of eliminated spines in the bilateral sensory cortices increased and the rate of stable spines in the bilateral cortices declined at two weeks and one month. From three days to two weeks, the stable rates of bilaterally stable spines in the SCI group decreased. In comparison to the control group and contralateral cortex in the SCI group, the re-emerging rate of eliminated spines in ipsilateral cortex of the SCI group decreased significantly. The stable rates of newly formed spines in bilateral cortices of the SCI group decreased from two weeks to one month. We found that the remodeling in the hindlimb representation of the sensory cortex after spinal cord hemisection occurred bilaterally. This remodeling included eliminating spines and forming new spines, as well as changing the reorganized regions of the brain cortex after the SCI over time. Soon after the SCI, the cortex was remodeled by

  14. Neuronal Migration Dynamics in the Developing Ferret Cortex.

    PubMed

    Gertz, Caitlyn C; Kriegstein, Arnold R

    2015-10-21

    During mammalian neocortical development, newborn excitatory and inhibitory neurons must migrate over long distances to reach their final positions within the cortical plate. In the lissencephalic rodent brain, pyramidal neurons are born in the ventricular and subventricular zones of the pallium and migrate along radial glia fibers to reach the appropriate cortical layer. Although much less is known about neuronal migration in species with a gyrencephalic cortex, retroviral studies in the ferret and primate suggest that, unlike the rodent, pyramidal neurons do not follow strict radial pathways and instead can disperse horizontally. However, the means by which pyramidal neurons laterally disperse remain unknown. In this study, we identified a viral labeling technique for visualizing neuronal migration in the ferret, a gyrencephalic carnivore, and found that migration was predominantly radial at early postnatal ages. In contrast, neurons displayed more tortuous migration routes with a decreased frequency of cortical plate-directed migration at later stages of neurogenesis concomitant with the start of brain folding. This was accompanied by neurons migrating sequentially along several different radial glial fibers, suggesting a mode by which pyramidal neurons may laterally disperse in a folded cortex. These findings provide insight into the migratory behavior of neurons in gyrencephalic species and provide a framework for using nonrodent model systems for studying neuronal migration disorders. Elucidating neuronal migration dynamics in the gyrencephalic, or folded, cortex is important for understanding neurodevelopmental disorders. Similar to the rodent, we found that neuronal migration was predominantly radial at early postnatal ages in the gyrencephalic ferret cortex. Interestingly, ferret neurons displayed more tortuous migration routes and a decreased frequency of radial migration at later ages coincident with the start of cortical folding. We found that ferret

  15. Age-related changes of microcirculation in pia mater of rats' sensorimotor cortex.

    PubMed

    Sokolova, I B; Sergeev, I V; Fedotova, O R; Melnikova, N N; Dvoretsky, D P

    2016-01-01

    We studied the density of the microvascular network in the pia mater, the tissue perfusion and saturation of the oxygen of sensorimotor cortex of hypertensive rats of different ages. Our investigations shown that the microvascular density in the pia mater was not only decreased, but also was increased. The perfusion of sensorimotor cortex was reduced and tissue saturation was enlarged. By the age of 12 months orienting-exploratory rats behavior became worse significantly in all major indicators of the test «open field».

  16. Effects of naltrexone on firing activity of rat cortex neurons and its interactions with ethanol.

    PubMed

    Kozhechkin, S N; Mednikova, Yu S; Kolik, L G

    2013-09-01

    Naltrexone dose-dependently decreased neuron firing rate in the rat frontal cortex after intravenous (1-20 mg/kg) and microelectrophoretic administration. Microelectrophoretic applications of naltrexone reduced the excitatory neuronal response of neurons to low doses of ethanol (electroosmotic application) and potentiated depression of firing activity induced by ethanol in high doses. We concluded that opioid peptides take part in generation of spontaneous neuronal activity in the frontal cortex and neuronal excitation caused by ethanol in low doses. Naltrexone acts as a synergist of ethanol in its depressive effect on cortical neurons.

  17. 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

  18. 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.

  19. Auditory spatial processing in the human cortex.

    PubMed

    Salminen, Nelli H; Tiitinen, Hannu; May, Patrick J C

    2012-12-01

    The auditory system codes spatial locations in a way that deviates from the spatial representations found in other modalities. This difference is especially striking in the cortex, where neurons form topographical maps of visual and tactile space but where auditory space is represented through a population rate code. In this hemifield code, sound source location is represented in the activity of two widely tuned opponent populations, one tuned to the right and the other to the left side of auditory space. Scientists are only beginning to uncover how this coding strategy adapts to various spatial processing demands. This review presents the current understanding of auditory spatial processing in the cortex. To this end, the authors consider how various implementations of the hemifield code may exist within the auditory cortex and how these may be modulated by the stimulation and task context. As a result, a coherent set of neural strategies for auditory spatial processing emerges.

  20. Mapping receptive fields in primary visual cortex

    PubMed Central

    Ringach, Dario L

    2004-01-01

    Nearly 40 years ago, in the pages of this journal, Hubel and Wiesel provided the first description of receptive fields in the primary visual cortex of higher mammals. They defined two classes of cortical cells, ‘simple’ and ‘complex’, based on neural responses to simple visual stimuli. The notion of a hierarchy of receptive fields, where increasingly intricate receptive fields are constructed from more elementary ones, was introduced. Since those early days we have witnessed the birth of quantitative methods to map receptive fields and mathematical descriptions of simple and complex cell function. Insights gained from these models, along with new theoretical concepts, are refining our understanding of receptive field structure and the underlying cortical circuitry. Here, I provide a brief historical account of the evolution of receptive field mapping in visual cortex along with the associated conceptual advancements, and speculate on the shape novel theories of the cortex may take as a result these measurements. PMID:15155794

  1. Mismatch Receptive Fields in Mouse Visual Cortex.

    PubMed

    Zmarz, Pawel; Keller, Georg B

    2016-11-23

    In primary visual cortex, a subset of neurons responds when a particular stimulus is encountered in a certain location in visual space. This activity can be modeled using a visual receptive field. In addition to visually driven activity, there are neurons in visual cortex that integrate visual and motor-related input to signal a mismatch between actual and predicted visual flow. Here we show that these mismatch neurons have receptive fields and signal a local mismatch between actual and predicted visual flow in restricted regions of visual space. These mismatch receptive fields are aligned to the retinotopic map of visual cortex and are similar in size to visual receptive fields. Thus, neurons with mismatch receptive fields signal local deviations of actual visual flow from visual flow predicted based on self-motion and could therefore underlie the detection of objects moving relative to the visual flow caused by self-motion. VIDEO ABSTRACT.

  2. Spatial updating in human parietal cortex

    NASA Technical Reports Server (NTRS)

    Merriam, Elisha P.; Genovese, Christopher R.; Colby, Carol L.

    2003-01-01

    Single neurons in monkey parietal cortex update visual information in conjunction with eye movements. This remapping of stimulus representations is thought to contribute to spatial constancy. We hypothesized that a similar process occurs in human parietal cortex and that we could visualize it with functional MRI. We scanned subjects during a task that involved remapping of visual signals across hemifields. We observed an initial response in the hemisphere contralateral to the visual stimulus, followed by a remapped response in the hemisphere ipsilateral to the stimulus. We ruled out the possibility that this remapped response resulted from either eye movements or visual stimuli alone. Our results demonstrate that updating of visual information occurs in human parietal cortex.

  3. Controlling contractile instabilities in the actomyosin cortex

    PubMed Central

    Nishikawa, Masatoshi; Naganathan, Sundar Ram; Jülicher, Frank; Grill, Stephan W

    2017-01-01

    The actomyosin cell cortex is an active contractile material for driving cell- and tissue morphogenesis. The cortex has a tendency to form a pattern of myosin foci, which is a signature of potentially unstable behavior. How a system that is prone to such instabilities can rveliably drive morphogenesis remains an outstanding question. Here, we report that in the Caenorhabditis elegans zygote, feedback between active RhoA and myosin induces a contractile instability in the cortex. We discover that an independent RhoA pacemaking oscillator controls this instability, generating a pulsatory pattern of myosin foci and preventing the collapse of cortical material into a few dynamic contracting regions. Our work reveals how contractile instabilities that are natural to occur in mechanically active media can be biochemically controlled to robustly drive morphogenetic events. DOI: http://dx.doi.org/10.7554/eLife.19595.001 PMID:28117665

  4. Spatial updating in human parietal cortex

    NASA Technical Reports Server (NTRS)

    Merriam, Elisha P.; Genovese, Christopher R.; Colby, Carol L.

    2003-01-01

    Single neurons in monkey parietal cortex update visual information in conjunction with eye movements. This remapping of stimulus representations is thought to contribute to spatial constancy. We hypothesized that a similar process occurs in human parietal cortex and that we could visualize it with functional MRI. We scanned subjects during a task that involved remapping of visual signals across hemifields. We observed an initial response in the hemisphere contralateral to the visual stimulus, followed by a remapped response in the hemisphere ipsilateral to the stimulus. We ruled out the possibility that this remapped response resulted from either eye movements or visual stimuli alone. Our results demonstrate that updating of visual information occurs in human parietal cortex.

  5. Medial reward and lateral non-reward orbitofrontal cortex circuits change in opposite directions in depression.

    PubMed

    Cheng, Wei; Rolls, Edmund T; Qiu, Jiang; Liu, Wei; Tang, Yanqing; Huang, Chu-Chung; Wang, XinFa; Zhang, Jie; Lin, Wei; Zheng, Lirong; Pu, JunCai; Tsai, Shih-Jen; Yang, Albert C; Lin, Ching-Po; Wang, Fei; Xie, Peng; Feng, Jianfeng

    2016-12-01

    The first brain-wide voxel-level resting state functional connectivity neuroimaging analysis of depression is reported, with 421 patients with major depressive disorder and 488 control subjects. Resting state functional connectivity between different voxels reflects correlations of activity between those voxels and is a fundamental tool in helping to understand the brain regions with altered connectivity and function in depression. One major circuit with altered functional connectivity involved the medial orbitofrontal cortex Brodmann area 13, which is implicated in reward, and which had reduced functional connectivity in depression with memory systems in the parahippocampal gyrus and medial temporal lobe, especially involving the perirhinal cortex Brodmann area 36 and entorhinal cortex Brodmann area 28. The Hamilton Depression Rating Scale scores were correlated with weakened functional connectivity of the medial orbitofrontal cortex Brodmann area 13. Thus in depression there is decreased reward-related and memory system functional connectivity, and this is related to the depressed symptoms. The lateral orbitofrontal cortex Brodmann area 47/12, involved in non-reward and punishing events, did not have this reduced functional connectivity with memory systems. Second, the lateral orbitofrontal cortex Brodmann area 47/12 had increased functional connectivity with the precuneus, the angular gyrus, and the temporal visual cortex Brodmann area 21. This enhanced functional connectivity of the non-reward/punishment system (Brodmann area 47/12) with the precuneus (involved in the sense of self and agency), and the angular gyrus (involved in language) is thus related to the explicit affectively negative sense of the self, and of self-esteem, in depression. A comparison of the functional connectivity in 185 depressed patients not receiving medication and 182 patients receiving medication showed that the functional connectivity of the lateral orbitofrontal cortex Brodmann

  6. Space representation in the prefrontal cortex.

    PubMed

    Funahashi, Shintaro

    2013-04-01

    The representation of space and its function in the prefrontal cortex have been examined using a variety of behavioral tasks. Among them, since the delayed-response task requires the temporary maintenance of spatial information, this task has been used to examine the mechanisms of spatial representation. In addition, the concept of working memory to explain prefrontal functions has helped us to understand the nature and functions of space representation in the prefrontal cortex. The detailed analysis of delay-period activity observed in spatial working memory tasks has provided important information for understanding space representation in the prefrontal cortex. Directional delay-period activity has been shown to be a neural correlate of the mechanism for temporarily maintaining information and represent spatial information for the visual cue and the saccade. In addition, many task-related prefrontal neurons exhibit spatially selective activities. These neurons are also important components of spatial information processing. In fact, information flow from sensory-related neurons to motor-related neurons has been demonstrated, along with a change in spatial representation as the trial progresses. The dynamic functional interactions among neurons exhibiting different task-related activities and representing different aspects of information could play an essential role in information processing. In addition, information provided from other cortical or subcortical areas might also be necessary for the representation of space in the prefrontal cortex. To better understand the representation of space and its function in the prefrontal cortex, we need to understand the nature of functional interactions between the prefrontal cortex and other cortical and subcortical areas.

  7. Perirhinal cortex and temporal lobe epilepsy

    PubMed Central

    Biagini, Giuseppe; D'Antuono, Margherita; Benini, Ruba; de Guzman, Philip; Longo, Daniela; Avoli, Massimo

    2013-01-01

    The perirhinal cortex—which is interconnected with several limbic structures and is intimately involved in learning and memory—plays major roles in pathological processes such as the kindling phenomenon of epileptogenesis and the spread of limbic seizures. Both features may be relevant to the pathophysiology of mesial temporal lobe epilepsy that represents the most refractory adult form of epilepsy with up to 30% of patients not achieving adequate seizure control. Compared to other limbic structures such as the hippocampus or the entorhinal cortex, the perirhinal area remains understudied and, in particular, detailed information on its dysfunctional characteristics remains scarce; this lack of information may be due to the fact that the perirhinal cortex is not grossly damaged in mesial temporal lobe epilepsy and in models mimicking this epileptic disorder. However, we have recently identified in pilocarpine-treated epileptic rats the presence of selective losses of interneuron subtypes along with increased synaptic excitability. In this review we: (i) highlight the fundamental electrophysiological properties of perirhinal cortex neurons; (ii) briefly stress the mechanisms underlying epileptiform synchronization in perirhinal cortex networks following epileptogenic pharmacological manipulations; and (iii) focus on the changes in neuronal excitability and cytoarchitecture of the perirhinal cortex occurring in the pilocarpine model of mesial temporal lobe epilepsy. Overall, these data indicate that perirhinal cortex networks are hyperexcitable in an animal model of temporal lobe epilepsy, and that this condition is associated with a selective cellular damage that is characterized by an age-dependent sensitivity of interneurons to precipitating injuries, such as status epilepticus. PMID:24009554

  8. Acute Alcohol Intoxication Decreases Glucose Metabolism but Increases Acetate Uptake in the Human Brain

    PubMed Central

    Volkow, Nora D.; Kim, Sung Won; Wang, Gene-Jack; Alexoff, David; Logan, Jean; Muench, Lisa; Shea, Colleen; Telang, Frank; Fowler, Joanna S.; Wong, Christopher; Benveniste, Helene; Tomasi, Dardo

    2012-01-01

    Alcohol intoxication results in marked reductions in brain glucose metabolism, which we hypothesized reflect not just its GABAergic enhancing effects but also metabolism of acetate as an alternative brain energy source. To test this hypothesis we separately assessed the effects of alcohol intoxication on brain glucose and acetate metabolism using Positron Emission Tomography (PET). We found that alcohol intoxication significantly decreased whole brain glucose metabolism (measured with FDG) with the largest decrements in cerebellum and occipital cortex and the smallest in thalamus. In contrast, alcohol intoxication caused a significant increase in [1-11C]acetate brain uptake (measured as standard uptake value, SUV), with the largest increases occurring in cerebellum and the smallest in thalamus. In heavy alcohol drinkers [1-11C]acetate brain uptake during alcohol challenge trended to be higher than in occasional drinkers (p <0.06) and the increases in [1-11C]acetate uptake in cerebellum with alcohol were positively associated with the reported amount of alcohol consumed (r=0.66, p<0.01). Our findings corroborate a reduction of brain glucose metabolism during intoxication and document an increase in brain acetate uptake. The opposite changes observed between regional brain metabolic decrements and regional increases in [1-11C]acetate uptake support the hypothesis that during alcohol intoxication the brain may rely on acetate as an alternative brain energy source and provides preliminary evidence that heavy alcohol exposures may facilitate the use of acetate as an energy substrate. These findings raise the question of the potential therapeutic benefits that increasing plasma acetate concentration (ie ketogenic diets) may have in alcoholics undergoing alcohol detoxification. PMID:22947541

  9. Infralimbic cortex controls core body temperature in a histamine dependent manner.

    PubMed

    Riveros, M E; Perdomo, G; Torrealba, F

    2014-04-10

    An increase in body temperature accelerates biochemical reactions and behavioral and physiological responses. A mechanism to actively increase body temperature would be beneficial during motivated behaviors. The prefrontal cortex is implicated in organizing motivated behavior; the infralimbic cortex, a subregion of the medial prefrontal cortex, has the necessary connectivity to serve the role of initiating such thermogenic mechanism at the beginning of the appetitive phase of motivated behavior; further, this cortex is active during motivated behavior and its disinhibition produces a marked behavioral and vegetative arousal increase, together with increases in histamine levels. We wanted to explore if this arousal was related to histaminergic activation after pharmacological infralimbic disinhibition and during the appetitive phase of motivated behavior. We measured core temperature and motor activity in response to picrotoxin injection in the infralimbic cortex, as well as during food-related appetitive behavior, evoked by enticing hungry rats with food. Pretreatment with the H1 receptor antagonist pyrilamine decreased thermal response to picrotoxin and enticement and completely blunted motor response to enticement. Motor and temperature responses to enticement were also completely abolished by infralimbic cortex inhibition with muscimol. To assess if this histamine dependent temperature increase was produced by an active sympathetic mediated thermogenic mechanism or was just a consequence of increased locomotor activity, we injected propranolol (i.p.), a β adrenergic receptor blocker, before picrotoxin injection into the infralimbic cortex. Propranolol reduced the temperature increase without affecting locomotor activity. Altogether, these results suggest that infralimbic activation is necessary for appetitive behavior by inducing a motor and a vegetative arousal increase mediated by central histamine. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Phonetic invariance in the human auditory cortex.

    PubMed

    Aulanko, R; Hari, R; Lounasmaa, O V; Näätänen, R; Sams, M

    1993-09-30

    Neuromagnetic signals evoked by synthesized syllables (/bae/ and /gae/) were recorded over the left auditory cortex of healthy humans. The fundamental frequencies of the syllables varied as if the same speaker had pronounced them at 16 different pitches. Specific mismatch responses to infrequent syllables among frequent syllables of the other type indicated that phonetically invariant information had been extracted at the level of the auditory cortex from the extensive irrelevant pitch variation. Such a detection mechanism is necessary for perceiving speech sounds in natural situations with a great deal of acoustic variation present.

  11. Dopamine depletion of the prefrontal cortex induces dendritic spine loss: reversal by atypical antipsychotic drug treatment.

    PubMed

    Wang, Hui-Dong; Deutch, Ariel Y

    2008-05-01

    Dystrophic changes in dendrites of cortical neurons are present in several neuro-psychiatric disorders, including schizophrenia. The mechanisms that account for dendritic changes in the prefrontal cortex (PFC) in schizophrenia are unclear. Cognitive deficits in schizophrenia have been linked to compromised cortical dopamine function, and the density of the PFC dopamine innervation is decreased in schizophrenia. We determined if 6-hydroxydopamine lesions of the ventral tegmental area that disrupt the PFC dopamine innervation cause dystrophic changes in cortical neurons. Three weeks post-operatively we observed a marked decrease in basal dendritic length and spine density of layer V pyramidal cells in the prelimbic cortex; no change was seen in neurons of the motor cortex. We then examined rats in which the PFC dopamine innervation was lesioned and 3 weeks later were started on chronic treatment with an atypical (olanzapine) or typical (haloperidol) antipsychotic drug. Olanzapine but not haloperidol reversed lesion-induced changes in PFC pyramidal cell dendrites. These data suggest that dopamine regulates dendritic structure in PFC neurons. Moreover, the findings are consistent with a decrease in cortical dopaminergic tone contributing to the pathological changes in the cortex of schizophrenia, and suggest that the progressive cortical loss in schizophrenia may be slowed or reversed by treatment with atypical antipsychotic drugs.

  12. Prefrontal Cortex and Somatosensory Cortex in Tactile Crossmodal Association: An Independent Component Analysis of ERP Recordings

    PubMed Central

    Wang, Liping; Lenz, Fred A.; Hsiao, Steven S.; Bodner, Mark; Hong, Bo; Zhou, Yong-Di

    2007-01-01

    Our previous studies on scalp-recorded event-related potentials (ERPs) showed that somatosensory N140 evoked by a tactile vibration in working memory tasks was enhanced when human subjects expected a coming visual stimulus that had been paired with the tactile stimulus. The results suggested that such enhancement represented the cortical activities involved in tactile-visual crossmodal association. In the present study, we further hypothesized that the enhancement represented the neural activities in somatosensory and frontal cortices in the crossmodal association. By applying independent component analysis (ICA) to the ERP data, we found independent components (ICs) located in the medial prefrontal cortex (around the anterior cingulate cortex, ACC) and the primary somatosensory cortex (SI). The activity represented by the IC in SI cortex showed enhancement in expectation of the visual stimulus. Such differential activity thus suggested the participation of SI cortex in the task-related crossmodal association. Further, the coherence analysis and the Granger causality spectral analysis of the ICs showed that SI cortex appeared to cooperate with ACC in attention and perception of the tactile stimulus in crossmodal association. The results of our study support with new evidence an important idea in cortical neurophysiology: higher cognitive operations develop from the modality-specific sensory cortices (in the present study, SI cortex) that are involved in sensation and perception of various stimuli. PMID:17712419

  13. Vertical transmission of Zika virus targeting the radial glial cells affects cortex development of offspring mice

    PubMed Central

    Wu, Kong-Yan; Zuo, Guo-Long; Li, Xiao-Feng; Ye, Qing; Deng, Yong-Qiang; Huang, Xing-Yao; Cao, Wu-Chun; Qin, Cheng-Feng; Luo, Zhen-Ge

    2016-01-01

    The recent Zika virus (ZIKV) epidemic in Latin America coincided with a marked increase in microcephaly in newborns. However, the causal link between maternal ZIKV infection and malformation of the fetal brain has not been firmly established. Here we show a vertical transmission of ZIKV in mice and a marked effect on fetal brain development. We found that intraperitoneal (i.p.) injection of a contemporary ZIKV strain in pregnant mice led to the infection of radial glia cells (RGs) of dorsal ventricular zone of the fetuses, the primary neural progenitors responsible for cortex development, and caused a marked reduction of these cortex founder cells in the fetuses. Interestingly, the infected fetal mice exhibited a reduced cavity of lateral ventricles and a discernable decrease in surface areas of the cortex. This study thus supports the conclusion that vertically transmitted ZIKV affects fetal brain development and provides a valuable animal model for the evaluation of potential therapeutic or preventative strategies. PMID:27174054

  14. Effect of central neurotropic substances on the hypophysisadrenal cortex system during immobilization of animals

    NASA Technical Reports Server (NTRS)

    Ryzhenkov, V. Y.

    1980-01-01

    The immobilization of guinea pigs for 5, 12, 24 and 48 hours, by securing to a slab, results in a persistent rise of the blood plasma 17-oxycorticosteroid concentration. Repeated administration of phenobarbital (50 mg/kg) and of the sodium salt of gamma-oxybutyric acid (500 mg/kg), as well as the combined administration of central m- and n-cholinolytics with small doses of phenobarbital tends to inhibit activation of the adrenal cortex during 48 hour immobilization of the animals. Repeated administration of aminazine (20 mg/kg) tends to decrease activation of the adrenal cortex. The administration of reserpine (0.1-5 mg/kg) 12-18 hours before immobilization of guinea pigs increases the response of the hypophysis-adrenal cortex system.

  15. Effects of lindane on the glucose metabolism in rat brain cortex cells

    SciTech Connect

    Pulido, J.A.; del Hoyo, N.; Perez-Albarsanz, M.A. )

    1990-01-01

    The influence of 0.5 mM {gamma}-hexachlorocyclohexane ({gamma}-HCH, lindane) on glucose transport has been investigated using the analog 3-O-methyl-D(U-{sup 14}C) glucose. The glucose uptake was lineal for at least 10 sec. Preincubation of dissociated brain cortex cells with lindane decreased the transport of glucose with respect to the controls. The treatment of brain cortex cells with other organochlorine compounds indicated that the {alpha}-, {delta}-HCH isomers and dieldrin reproduced the same inhibitory pattern, while {beta}-HCH and endrin were inactive. The total radioactivity incorporated into CO{sub 2} from (U-{sup 14}C) glucose in the cerebral cortex is also inhibited by lindane in a time dependent manner.

  16. Effect of externally added carnitine on the synthesis of acetylcholine in rat cerebral cortex cells.

    PubMed

    Wawrzeńczyk, A; Nałecz, K A; Nałecz, M J

    1995-06-01

    Acetylcholine synthesis from radiolabelled glucose was monitored in cerebral cortex cells isolated from brains of suckling and adult rats. Acetylcholine synthesis was found much higher in suckling animals, both in the absence and presence of acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) inhibitor, paraoxon. Together with choline (20 microM), carnitine was found to stimulate acetylcholine synthesis in a synergistic way in cortex cells from adult rats (18%). Choline, however, was incapable of reversing an inhibitory effect exerted by carnitine on acetylcholine synthesis in cortex cells from suckling animals. Distribution of carnitine derivatives was found significantly different in the cells from young and old animals, the content of acetylcarnitine decreased with age with a corresponding increase of free carnitine. The observed differences in carnitine effect on acetylcholine synthesis suggested that high acetylcarnitine in cells capable of beta-oxidation might be correlated with the lower level of acetylcholine synthesis.

  17. The involvement of Nek2 and Notch in the proliferation of rat adrenal cortex triggered by POMC-derived peptides.

    PubMed

    de Mendonca, Pedro Omori Ribeiro; Costa, Ismael Cabral; Lotfi, Claudimara Ferini Pacicco

    2014-01-01

    The adrenal gland is a dynamic organ that undergoes constant cell turnover. This allows for rapid organ remodeling in response to the physiological demands of the HPA axis, which is controlled by proopiomelanocortin (POMC)-derived peptides, such as adrenocorticotropic hormone (ACTH) and N-Terminal peptides (N-POMC). In the rat adrenal cortex, POMC-derived peptides trigger a mitogenic effect, and this process increases cyclins D and E, while inhibiting p27Kip1. The goal of the present study was to further explore the mitogenic effect of ACTH and synthetic N-POMC1-28 peptides by investigating the differences in the expression of key genes involved in the cell cycle of the rat adrenal cortex, following inhibition of the HPA axis. Moreover, we evaluated the differences between the inner and outer fractions of the adrenal cortex (ZF-fraction and ZG-fraction) in terms of their response patterns to different stimuli. In the current study, the inhibition of the HPA axis repressed the expression of Ccnb2, Camk2a, and Nek2 genes throughout the adrenal cortex, while treatments with POMC-derived peptides stimulated Nek2, gene and protein expression, and Notch2 gene expression. Furthermore, Notch1 protein expression was restricted to the subcapsular region of the cortex, an area of the adrenal cortex that is well-known for proliferation. We also showed that different regions of the adrenal cortex respond to HPA-axis inhibition and to induction with POMC-derived peptides at different times. These results suggest that cells in the ZG and ZF fractions could be at different phases of the cell cycle. Our results contribute to the understanding of the mechanisms involved in cell cycle regulation in adrenocortical cells triggered by N-POMC peptides and ACTH, and highlight the involvement of genes such as Nek2 and Notch.

  18. A disinhibitory microcircuit initiates critical period plasticity in visual cortex

    PubMed Central

    Kuhlman, Sandra J.; Olivas, Nicholas D.; Tring, Elaine; Ikrar, Taruna; Xu, Xiangmin; Trachtenberg, Joshua T.

    2014-01-01

    Early sensory experience instructs the maturation of neural circuitry in cortex 1,2. This has been extensively studied in the primary visual cortex where loss of vision to one eye permanently degrades cortical responsiveness to that eye 3,4, a phenomenon known as ocular dominance plasticity (ODP). Cortical inhibition mediates this process 4-6, but the precise role of specific classes of inhibitory neurons in ODP is controversial. Here we report that evoked firing rates of binocular excitatory neurons in primary visual cortex immediately drop by half when vision is restricted to one eye, but gradually return to normal over the following 24 hours, despite the fact that vision remains restricted to one eye. This restoration of binocular-like excitatory firing rates following monocular deprivation results from a rapid, though transient reduction in the firing rates of fast-spiking, parvalbumin-positive (PV) interneurons, which in turn can be attributed to a decrease in local excitatory circuit input onto PV interneurons. This reduction in PV cell evoked responses following monocular lid suture is restricted to the critical period for ODP and appears to be necessary for subsequent shifts in excitatory ODP. Pharmacologically enhancing inhibition at the time of sight deprivation blocks ODP and, conversely, pharmaco-genetic reduction of PV cell firing rates can extend the critical period for ODP. These findings define the microcircuit changes initiating competitive plasticity during critical periods of cortical development. Moreover, they show that the restoration of evoked firing rates of L2/3 pyramidal neurons by PV-specific disinhibition is a key step in the progression of ocular dominance plasticity. PMID:23975100

  19. Abnormal activation of the primary somatosensory cortex in spasmodic dysphonia: an fMRI study.

    PubMed

    Simonyan, Kristina; Ludlow, Christy L

    2010-11-01

    Spasmodic dysphonia (SD) is a task-specific focal dystonia of unknown pathophysiology, characterized by involuntary spasms in the laryngeal muscles during speaking. Our aim was to identify symptom-specific functional brain activation abnormalities in adductor spasmodic dysphonia (ADSD) and abductor spasmodic dysphonia (ABSD). Both SD groups showed increased activation extent in the primary sensorimotor cortex, insula, and superior temporal gyrus during symptomatic and asymptomatic tasks and decreased activation extent in the basal ganglia, thalamus, and cerebellum during asymptomatic tasks. Increased activation intensity in SD patients was found only in the primary somatosensory cortex during symptomatic voice production, which showed a tendency for correlation with ADSD symptoms. Both SD groups had lower correlation of activation intensities between the primary motor and sensory cortices and additional correlations between the basal ganglia, thalamus, and cerebellum during symptomatic and asymptomatic tasks. Compared with ADSD patients, ABSD patients had larger activation extent in the primary sensorimotor cortex and ventral thalamus during symptomatic task and in the inferior temporal cortex and cerebellum during symptomatic and asymptomatic voice production. The primary somatosensory cortex shows consistent abnormalities in activation extent, intensity, correlation with other brain regions, and symptom severity in SD patients and, therefore, may be involved in the pathophysiology of SD.

  20. Effect of the cortex on ultrasonic backscatter measurements of cancellous bone.

    PubMed

    Hoffmeister, Brent K; Holt, Andrew P; Kaste, Sue C

    2011-10-07

    Ultrasonic backscatter techniques offer a promising new approach for detecting changes in bone caused by osteoporosis. However, several challenges impede clinical implementation of backscatter techniques. This study examines how the dense outer surface of bone (the cortex) affects backscatter measurements of interior regions of porous (cancellous) bone tissue. Fifty-two specimens of bone were prepared from 13 human femoral heads so that the same region of cancellous bone could be ultrasonically interrogated through the cortex or along directions that avoided the cortex. Backscatter signals were analyzed over a frequency range of 0.8-3.0 MHz to determine two ultrasonic parameters: apparent integrated backscatter (AIB) and frequency slope of apparent backscatter (FSAB). The term 'apparent' means that the parameters are sensitive to the frequency-dependent effects of diffraction and attenuation. Significant (p < 0.001) changes in AIB and FSAB indicated that measurements through the cortex decreased the apparent backscattered power and increased the frequency dependence of the power. However, the cortex did not affect the correlation of AIB and FSAB with the x-ray bone mineral density of the specimens. This suggests that results from many previous in vitro backscatter studies of specimens of purely cancellous bone may be extrapolated with greater confidence to in vivo conditions.

  1. No Modulation of Visual Cortex Excitability by Transcranial Direct Current Stimulation.

    PubMed

    Brückner, Sabrina; Kammer, Thomas

    2016-01-01

    Measuring phosphene thresholds (PTs) is often used to investigate changes in the excitability of the human visual cortex through different brain stimulation methods like repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS). In several studies, PT increase or decrease has been shown after rTMS or tDCS application. Recently, using PT measurements we showed that the state of the neurons in the visual cortex after rTMS might have an influence on the modulatory effects of stimulation. In the present study we aimed to investigate whether visual cortex activity following stimulation influences the modulatory effects of tDCS as well. In a between-group design, anodal or cathodal tDCS was applied to the visual cortex twice per subject, with either high or low visual demand following stimulation. We observed no modulation of PT neither directly following both anodal and cathodal tDCS nor following the visual demand periods. We rather found high inter-individual variability in the response to tDCS, and intra-individual reliability in the direction of modulation was observed for cathodal tDCS only. Thus, our results do not confirm the modulatory effects of tDCS on visual cortex excitability published previously. Moreover, they support the confirmation that tDCS effects have little reliability on varied TMS outcome measurements.

  2. Complementary activation of the ipsilateral primary motor cortex during a sustained handgrip task.

    PubMed

    Shibuya, Kenichi; Kuboyama, Naomi; Yamada, Seigo

    2016-01-01

    Near-infrared spectroscopy (NIRS) can be used to examine bilateral motor cortex activation during a sustained motor task in brain areas where increased oxygenation reflects cortical activation. This study examines the time course of activation of the bilateral motor cortex during a moderate-intensity handgrip task. Ten healthy right-handed male subjects participated in this study. Functional NIRS probes were placed over the cortex to measure motor cortical activations while the subjects performed a 180-s handgrip task incrementally [30-60% of the maximal voluntary contraction (MVC) at 0.17% increase/s] Contralateral primary motor cortex (ContraM1) oxygenation values significantly increased from baseline between 40 and 120 s after the start of the motor task (p < 0.05). Moreover, the ipsilateral primary motor cortex (IpsiM1) oxygenation values significantly increased from baseline between 140 and 180 s after the start of the motor task (p < 0.05). IpsiM1 oxygenation gradually increased from 140 to 180 s, whereas ContraM1 oxygenation gradually decreased from 120 to 180 s after the start of the motor task. These results suggest that the complementary functions of IpsiM1 become activated in response to the working of the ContraM1 during a continuous handgrip task.

  3. Mapping the relationship between subgenual cingulate cortex functional connectivity and depressive symptoms across adolescence

    PubMed Central

    Strikwerda-Brown, Cherie; Davey, Christopher G.; Whittle, Sarah; Allen, Nicholas B.; Byrne, Michelle L.; Schwartz, Orli S.; Simmons, Julian G.; Dwyer, Dominic

    2015-01-01

    Changes in the functional connectivity of the subgenual anterior cingulate cortex (SGC) have been linked with depressive symptoms. The aim of this study was to map this relationship across mid to late adolescence. Employing a longitudinal functional magnetic resonance imaging (fMRI) design, associations between patterns of resting-state SGC functional connectivity and symptoms of depression were examined at two time points in an initial sample of 72 adolescents. Using a region-of-interest approach, these associations were evaluated cross-sectionally and longitudinally. Cross-sectionally, weaker SGC functional connectivity with the posterior cingulate cortex (PCC), angular gyrus and dorsal prefrontal cortex at baseline, and weaker SGC connectivity with the dorsomedial prefrontal cortex (DMPFC) and ventromedial prefrontal cortex at follow-up, were associated with higher depressive symptoms. Longitudinally, a decrease in SGC functional connectivity with DMPFC, PCC, angular gyrus and middle temporal gyrus was associated with higher depressive symptoms at follow-up. The observation of weaker SGC connectivity predicting increased symptoms contrasts with the majority of resting-state fMRI studies in clinically depressed populations. Taken together with these past studies, our findings suggest depression-related changes in SGC functional connectivity may differ across developmental and illness stages. PMID:25416726

  4. Chronic treadmill running does not enhance mitochondrial oxidative capacity in the cortex or striatum.

    PubMed

    Herbst, Eric A F; Roussakis, Christina; Matravadia, Sarthak; Holloway, Graham P

    2015-11-01

    The aims of the present study were to determine in healthy animals if 1) acute exercise stimulated traditional exercise signaling pathways in the cortex and striatum, and 2) if chronic exercise training increased the oxidative capacity of these brain regions. Male C57BL/6 mice were left sedentary, acutely exercised for 15 or 60 min to examine potential signaling cascades activated by exercise, or chronically exercise for 4 wk to examine the impact of prolonged training. The cortex and striatum were analyzed for changes in the phosphorylation of AMPK, CAMKII, ERK1/2, and P38 with acute exercise, or markers of mitochondrial protein content, mtDNA copy number, and mitochondrial respiration with chronic exercise. In mice, acute treadmill running did not alter the phosphorylation of AMPK, CAMKII, or P38 in either the cortex or the striatum, but decreased ERK1/2 phosphorylation in only the cortex for the duration of the exercise bout. Following chronic exercise training, mitochondrial respiration, mtDNA copy number, and protein content of various subunits of the electron transport chain were not altered in adult mice. Combined, these data suggest that exercise does not result in increased phosphorylation of traditional signaling kinases or enhanced mitochondrial oxidative capacity in either the cortex or the striatum of healthy animals. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2014-09-19

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

  6. Early down regulation of the glial Kir4.1 and GLT-1 expression in pericontusional cortex of the old male mice subjected to traumatic brain injury.

    PubMed

    Gupta, R K; Prasad, S

    2013-10-01

    Astroglia play multiple roles in brain function by providing matrix to neurons, secreting neurotrophic factors, maintaining K(+) and glutamate homeostasis and thereby controlling synaptic plasticity which undergoes alterations during aging. K(+) and glutamate homeostasis is maintained by astrocytes membrane bound inwardly rectifying K(+) channel (Kir4.1) and glutamate transporter-1 (GLT-1 or EAAT-2) proteins, respectively in the synapse and their expression may be altered due to traumatic brain injury (TBI). Also, it is not well understood whether this change is age dependent. To find out this, TBI was experimentally induced in adult and old male AKR strain mice using CHI technique, and expression of the Kir4.1 and GLT-1 in the pericontusional cortex at various time intervals was studied by Western blotting and semi quantitative RT-PCR techniques. Here, we report that expression of both Kir4.1 and GLT-1 genes at transcript and protein levels is significantly down regulated in the pericontusional ipsi-lateral cortex of old TBI mice as compared to that in the adult TBI mice as function of time after injury. Further, expression of both the genes starts decreasing early in old mice i.e., from the first hour after TBI as compared to that starts from fourth hour in adult TBI mice. Thus TBI affects expression of Kir4.1 and GLT-1 genes in age- and time dependent manner and it may lead to accumulations of more K(+) and glutamate early in the synapse of old mice as compared to adult. This may be implicated in the TBI induced early and severe neuronal depolarization and excito-neurotoxicity in old age.

  7. Lymphedema treatment decreases pain intensity in lipedema.

    PubMed

    Szolnoky, G; Varga, E; Varga, M; Tuczai, M; Dósa-Rácz, E; Kemény, L

    2011-12-01

    Lipedema is a disproportional obesity featuring light pressure-induced or spontaneous pain. On the basis of our clinical observations, lymphedema therapy, as practiced in our clinic, reduces the perception of pain beyond leg volume reduction. We therefore aimed to measure pain intensity prior and subsequent to treatment. 38 women with lipedema were enrolled in the study with 19 patients undergoing treatment and 19 serving as the control group using exclusively moisturizers. Treatment consisted of once daily manual lymph drainage (MLD), intermittent pneumatic compression (IPC), and multilayered short-stretch bandaging performed throughout a 5-day-course. Pain was evaluated with a 10-item questionnaire, a pain rating scale (PRS), and the Wong-Baker Faces scale. Treatment resulted in a significant reduction of pain with a decrease in mean scores of all three measures. In the control group, only PRS showed significant decrease. Our study results indicate that this treatment regimen not only reduces leg volume and capillary fragility, but also improves pain intensity in patients with lipedema.

  8. Multiple Transient Signals in Human Visual Cortex Associated with an Elementary Decision

    PubMed Central

    Nolte, Guido

    2017-01-01

    The cerebral cortex continuously undergoes changes in its state, which are manifested in transient modulations of the cortical power spectrum. Cortical state changes also occur at full wakefulness and during rapid cognitive acts, such as perceptual decisions. Previous studies found a global modulation of beta-band (12–30 Hz) activity in human and monkey visual cortex during an elementary visual decision: reporting the appearance or disappearance of salient visual targets surrounded by a distractor. The previous studies disentangled neither the motor action associated with behavioral report nor other secondary processes, such as arousal, from perceptual decision processing per se. Here, we used magnetoencephalography in humans to pinpoint the factors underlying the beta-band modulation. We found that disappearances of a salient target were associated with beta-band suppression, and target reappearances with beta-band enhancement. This was true for both overt behavioral reports (immediate button presses) and silent counting of the perceptual events. This finding indicates that the beta-band modulation was unrelated to the execution of the motor act associated with a behavioral report of the perceptual decision. Further, changes in pupil-linked arousal, fixational eye movements, or gamma-band responses were not necessary for the beta-band modulation. Together, our results suggest that the beta-band modulation was a top-down signal associated with the process of converting graded perceptual signals into a categorical format underlying flexible behavior. This signal may have been fed back from brain regions involved in decision processing to visual cortex, thus enforcing a “decision-consistent” cortical state. SIGNIFICANCE STATEMENT Elementary visual decisions are associated with a rapid state change in visual cortex, indexed by a modulation of neural activity in the beta-frequency range. Such decisions are also followed by other events that might affect the state

  9. Cerebellum to motor cortex paired associative stimulation induces bidirectional STDP-like plasticity in human motor cortex.

    PubMed

    Lu, Ming-Kuei; Tsai, Chon-Haw; Ziemann, Ulf

    2012-01-01

    The cerebellum is crucially important for motor control and adaptation. Recent non-invasive brain stimulation studies have indicated the possibility to alter the excitability of the cerebellum and its projections to the contralateral motor cortex, with behavioral consequences on motor control and adaptation. Here we sought to induce bidirectional spike-timing dependent plasticity (STDP)-like modifications of motor cortex (M1) excitability by application of paired associative stimulation (PAS) in healthy subjects. Conditioning stimulation over the right lateral cerebellum (CB) preceded focal transcranial magnetic stimulation (TMS) of the left M1 hand area at an interstimulus interval of 2 ms (CB→M1 PAS(2 ms)), 6 ms (CB→M1 PAS(6 ms)) or 10 ms (CB→M1 PAS(10 ms)) or randomly alternating intervals of 2 and 10 ms (CB→M1 PAS(Control)). Effects of PAS on M1 excitability were assessed by the motor-evoked potential (MEP) amplitude, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cerebellar-motor cortex inhibition (CBI) in the first dorsal interosseous muscle of the right hand. CB→M1 PAS(2 ms) resulted in MEP potentiation, CB→M1 PAS(6 ms) and CB→M1 PAS(10 ms) in MEP depression, and CB→M1 PAS(Control) in no change. The MEP changes lasted for 30-60 min after PAS. SICI and CBI decreased non-specifically after all PAS protocols, while ICF remained unaltered. The physiological mechanisms underlying these MEP changes are carefully discussed. Findings support the notion of bidirectional STDP-like plasticity in M1 mediated by associative stimulation of the cerebello-dentato-thalamo-cortical pathway and M1. Future studies may investigate the behavioral significance of this plasticity.

  10. Dynamics of 3D view invariance in monkey inferotemporal cortex.

    PubMed

    Ratan Murty, N Apurva; Arun, Sripati P

    2015-04-01

    Rotations in depth are challenging for object vision because features can appear, disappear, be stretched or compressed. Yet we easily recognize objects across views. Are the underlying representations view invariant or dependent? This question has been intensely debated in human vision, but the neuronal representations remain poorly understood. Here, we show that for naturalistic objects, neurons in the monkey inferotemporal (IT) cortex undergo a dynamic transition in time, whereby they are initially sensitive to viewpoint and later encode view-invariant object identity. This transition depended on two aspects of object structure: it was strongest when objects foreshortened strongly across views and were similar to each other. View invariance in IT neurons was present even when objects were reduced to silhouettes, suggesting that it can arise through similarity between external contours of objects across views. Our results elucidate the viewpoint debate by showing that view invariance arises dynamically in IT neurons out of a representation that is initially view dependent. Copyright © 2015 the American Physiological Society.

  11. Differential Development of the Ventral Visual Cortex Extends Through Adolescence

    PubMed Central

    Golarai, Golijeh; Liberman, Alina; Yoon, Jennifer M. D.; Grill-Spector, Kalanit

    2009-01-01

    The ventral temporal cortex (VTC) in humans includes functionally defined regions that preferentially respond to objects, faces, and places. Recent developmental studies suggest that the face selective region in the fusiform gyrus (‘fusiform face area’, FFA) undergoes a prolonged development involving substantial increases in its volume after 7 years of age. However, the endpoint of this development is not known. Here we used functional magnetic resonance imaging (fMRI) to examine the development of face-, object- and place selective regions in the VTC of adolescents (12–16 year olds) and adults (18–40 year olds). We found that the volume of face selective activations in the right fusiform gyrus was substantially larger in adults than in adolescents, and was positively correlated with age. This development was associated with higher response amplitudes and selectivity for faces in face selective regions of VTC and increased differentiation of the distributed response patterns to faces versus non-face stimuli across the entire VTC. Furthermore, right FFA size was positively correlated with face recognition memory performance, but not with recognition memory of objects or places. In contrast, the volume of object- and place selective cortical regions or their response amplitudes did not change across these age groups. Thus, we found a striking and prolonged development of face selectivity across the VTC during adolescence that was specifically associated with proficiency in face recognition memory. These findings have important implications for theories of development and functional specialization in VTC. PMID:20204140

  12. Lithium/pilocarpine status epilepticus-induced neuropathology of piriform cortex and adjoining structures in rats is age-dependent.

    PubMed

    Druga, R; Kubová, H; Suchomelová, L; Haugvicová, R

    2003-01-01

    Distribution of LiCl/pilocarpine status epilepticus-induced neuronal damage was studied in the piriform cortex and in adjoining structures in 12-day-old, 25-day-old and adult rats. No distinct structural and neuronal alterations were detected in the basal telencephalon in 12-day-old rats surviving status epilepticus (SE) for one week or two months. In 25-day-old rats a decrease in Nissl staining was evident. There was also cell loss and gliosis in the caudal 2/3 of the piriform cortex, in the superficial amygdaloid nuclei, in the dorsal and ventral endopiriform nucleus and in the rostrolateral part of the entorhinal cortical area. In adult animals, the topography of neuropathological changes in the basal telencephalon was comparable to those in 25-day-old rats. The damage in the caudal 2/3 or caudal half of the piriform cortex in adult rats with survival times one week or two months was characterized by a marked loss of neurons and striking glial infiltration. The thickness of the piriform cortex and superficial amygdaloid nuclei was significantly reduced. In 25-day-old and in adult animals the sublayer IIb and layer III of the piriform cortex was more affected, while sublayer IIa was less damaged. Parvalbumin (PV) immunocytochemistry revealed a significant decrease in the number of PV-immunoreactive neurons in the rostral piriform cortex and in the dorsal claustrum in animals surviving for two months.

  13. Microglia in the Cerebral Cortex in Autism

    ERIC Educational Resources Information Center

    Tetreault, Nicole A.; Hakeem, Atiya Y.; Jiang, Sue; Williams, Brian A.; Allman, Elizabeth; Wold, Barbara J.; Allman, John M.

    2012-01-01

    We immunocytochemically identified microglia in fronto-insular (FI) and visual cortex (VC) in autopsy brains of well-phenotyped subjects with autism and matched controls, and stereologically quantified the microglial densities. Densities were determined blind to phenotype using an optical fractionator probe. In FI, individuals with autism had…

  14. Motor Cortex Reorganization across the Lifespan

    ERIC Educational Resources Information Center

    Plowman, Emily K.; Kleim, Jeffrey A.

    2010-01-01

    The brain is a highly dynamic structure with the capacity for profound structural and functional change. Such neural plasticity has been well characterized within motor cortex and is believed to represent one of the neural mechanisms for acquiring and modifying motor behaviors. A number of behavioral and neural signals have been identified that…

  15. Primary Auditory Cortex Regulates Threat Memory Specificity

    ERIC Educational Resources Information Center

    Wigestrand, Mattis B.; Schiff, Hillary C.; Fyhn, Marianne; LeDoux, Joseph E.; Sears, Robert M.

    2017-01-01

    Distinguishing threatening from nonthreatening stimuli is essential for survival and stimulus generalization is a hallmark of anxiety disorders. While auditory threat learning produces long-lasting plasticity in primary auditory cortex (Au1), it is not clear whether such Au1 plasticity regulates memory specificity or generalization. We used…

  16. Excitatory neuronal connectivity in the barrel cortex

    PubMed Central

    Feldmeyer, Dirk

    2012-01-01

    Neocortical areas are believed to be organized into vertical modules, the cortical columns, and the horizontal layers 1–6. In the somatosensory barrel cortex these columns are defined by the readily discernible barrel structure in layer 4. Information processing in the neocortex occurs along vertical and horizontal axes, thereby linking individual barrel-related columns via axons running through the different cortical layers of the barrel cortex. Long-range signaling occurs within the neocortical layers but also through axons projecting through the white matter to other neocortical areas and subcortical brain regions. Because of the ease of identification of barrel-related columns, the rodent barrel cortex has become a prototypical system to study the interactions between different neuronal connections within a sensory cortical area and between this area and other cortical as well subcortical regions. Such interactions will be discussed specifically for the feed-forward and feedback loops between the somatosensory and the somatomotor cortices as well as the different thalamic nuclei. In addition, recent advances concerning the morphological characteristics of excitatory neurons and their impact on the synaptic connectivity patterns and signaling properties of neuronal microcircuits in the whisker-related somatosensory cortex will be reviewed. In this context, their relationship between the structural properties of barrel-related columns and their function as a module in vertical synaptic signaling in the whisker-related cortical areas will be discussed. PMID:22798946

  17. The Piriform Cortex and Human Focal Epilepsy

    PubMed Central

    Vaughan, David N.; Jackson, Graeme D.

    2014-01-01

    It is surprising that the piriform cortex, when compared to the hippocampus, has been given relatively little significance in human epilepsy. Like the hippocampus, it has a phylogenetically preserved three-layered cortex that is vulnerable to excitotoxic injury, has broad connections to both limbic and cortical areas, and is highly epileptogenic – being critical to the kindling process. The well-known phenomenon of early olfactory auras in temporal lobe epilepsy highlights its clinical relevance in human beings. Perhaps because it is anatomically indistinct and difficult to approach surgically, as it clasps the middle cerebral artery, it has, until now, been understandably neglected. In this review, we emphasize how its unique anatomical and functional properties, as primary olfactory cortex, predispose it to involvement in focal epilepsy. From recent convergent findings in human neuroimaging, clinical epileptology, and experimental animal models, we make the case that the piriform cortex is likely to play a facilitating and amplifying role in human focal epileptogenesis, and may influence progression to epileptic intractability. PMID:25538678

  18. Developmental Outcomes after Early Prefrontal Cortex Damage

    ERIC Educational Resources Information Center

    Eslinger, Paul J.; Flaherty-Craig, Claire V.; Benton, Arthur L.

    2004-01-01

    The neuropsychological bases of cognitive, social, and moral development are minimally understood, with a seemingly wide chasm between developmental theories and brain maturation models. As one approach to bridging ideas in these areas, we review 10 cases of early prefrontal cortex damage from the clinical literature, highlighting overall clinical…

  19. Motor cortex inhibition induced by acoustic stimulation.

    PubMed

    Kühn, Andrea A; Sharott, Andrew; Trottenberg, Thomas; Kupsch, Andreas; Brown, Peter

    2004-09-01

    The influence of the brainstem motor system on cerebral motor areas may play an important role in motor control in health and disease. A new approach to investigate this interaction in man is combining acoustic stimulation activating the startle system with transcranial magnetic stimulation (TMS) over the motor cortex. However, it is unclear whether the inhibition of TMS responses following acoustic stimulation occurs at the level of the motor cortex through reticulo-cortical projections or subcortically, perhaps through reticulo-spinal projections. We compared the influence of acoustic stimulation on motor effects elicited by TMS over motor cortical areas to those evoked with subcortical electrical stimulation (SES) through depth electrodes in five patients treated with deep brain stimulation for Parkinson's disease. SES bypasses the motor cortex, demonstrating any interaction with acoustic stimuli at the subcortical level. EMG was recorded from the contralateral biceps brachii muscle. Acoustic stimulation was delivered binaurally through headphones and used as a conditioning stimulus at an interstimulus interval of 50 ms. When TMS was used as the test stimulus, the area and amplitude of the conditioned motor response was significantly inhibited (area: 57.5+/-12.9%, amplitude: 47.9+/-7.4%, as percentage of unconditioned response) whereas facilitation occurred with SES (area: 110.1+/-4.3%, amplitude: 116.9+/-6.9%). We conclude that a startle-evoked activation of reticulo-cortical projections transiently inhibits the motor cortex.

  20. Microglia in the Cerebral Cortex in Autism

    ERIC Educational Resources Information Center

    Tetreault, Nicole A.; Hakeem, Atiya Y.; Jiang, Sue; Williams, Brian A.; Allman, Elizabeth; Wold, Barbara J.; Allman, John M.

    2012-01-01

    We immunocytochemically identified microglia in fronto-insular (FI) and visual cortex (VC) in autopsy brains of well-phenotyped subjects with autism and matched controls, and stereologically quantified the microglial densities. Densities were determined blind to phenotype using an optical fractionator probe. In FI, individuals with autism had…

  1. Primary Auditory Cortex Regulates Threat Memory Specificity

    ERIC Educational Resources Information Center

    Wigestrand, Mattis B.; Schiff, Hillary C.; Fyhn, Marianne; LeDoux, Joseph E.; Sears, Robert M.

    2017-01-01

    Distinguishing threatening from nonthreatening stimuli is essential for survival and stimulus generalization is a hallmark of anxiety disorders. While auditory threat learning produces long-lasting plasticity in primary auditory cortex (Au1), it is not clear whether such Au1 plasticity regulates memory specificity or generalization. We used…

  2. Motor Cortex Reorganization across the Lifespan

    ERIC Educational Resources Information Center

    Plowman, Emily K.; Kleim, Jeffrey A.

    2010-01-01

    The brain is a highly dynamic structure with the capacity for profound structural and functional change. Such neural plasticity has been well characterized within motor cortex and is believed to represent one of the neural mechanisms for acquiring and modifying motor behaviors. A number of behavioral and neural signals have been identified that…

  3. [The importance of the cortex and subcortical structures of the brain in the perception of acute and chronic pain].

    PubMed

    Reschetniak, V K; Kukushkin, M L; Gurko, N S

    2014-01-01

    This review presents the current data in the literature about the importance of the cortex and subcortical structures of the brain in the perception of acute and chronic pain. Discussed the importance of various areas of the brain in perception discriminative and affective components of pain. Discusses also gender differences in pain perception depending on the functional activity of brain cortex and antinociceptive subcortical structures. Analyzed the morphological changes of cortical and subcortical structures of the brain in chronic pain syndromes. It is proved that the decrease in the volume of gray and white matter of cerebral cortex and subcortical structures is a consequence and not the cause of chronic pain syndrome. Discusses the features activate and deactivate certain areas of the cortex of the brain in acute and chronic pain. Analyzed same features the activation of several brain structures in migraine and cluster headache.

  4. Motion Direction Biases and Decoding in Human Visual Cortex

    PubMed Central

    Wang, Helena X.; Merriam, Elisha P.; Freeman, Jeremy

    2014-01-01

    Functional magnetic resonance imaging (fMRI) studies have relied on multivariate analysis methods to decode visual motion direction from measurements of cortical activity. Above-chance decoding has been commonly used to infer the motion-selective response properties of the underlying neural populations. Moreover, patterns of reliable response biases across voxels that underlie decoding have been interpreted to reflect maps of functional architecture. Using fMRI, we identified a direction-selective response bias in human visual cortex that: (1) predicted motion-decoding accuracy; (2) depended on the shape of the stimulus aperture rather than the absolute direction of motion, such that response amplitudes gradually decreased with distance from the stimulus aperture edge corresponding to motion origin; and 3) was present in V1, V2, V3, but not evident in MT+, explaining the higher motion-decoding accuracies reported previously in early visual cortex. These results demonstrate that fMRI-based motion decoding has little or no dependence on the underlying functional organization of motion selectivity. PMID:25209297

  5. Exon Microarray Analysis of Human Dorsolateral Prefrontal Cortex in Alcoholism

    PubMed Central

    Manzardo, Ann M.; Gunewardena, Sumedha; Wang, Kun; Butler, Merlin G.

    2014-01-01

    Background Alcohol abuse is associated with cellular and biochemical disturbances that impact upon protein and nucleic acid synthesis, brain development, function and behavioral responses. To further characterize the genetic influences in alcoholism and the effects of alcohol consumption on gene expression, we used a highly sensitive exon microarray to examine mRNA expression in human frontal cortex of alcoholics and control males. Methods Messenger RNA was isolated from the dorsolateral prefrontal cortex (dlPFC, Brodmann area 9) of 7 adult Alcoholic (6 males, 1 female, mean age 48 years) and 7 matched controls. Affymetrix Human Exon 1.0 ST Array was performed according to standard procedures and the results analyzed at the gene level. Microarray findings were validated using qRT-PCR, and the ontology of disturbed genes characterized using Ingenuity Pathway Analysis (IPA). Results Decreased mRNA expression was observed for genes involved in cellular adhesion (e.g., CTNNA3, ITGA2), transport (e.g., TF, ABCA8), nervous system development (e.g., LRP2, UGT8, GLDN) and signaling (e.g., RASGRP, LGR5) with influence over lipid and myelin synthesis (e.g., ASPA, ENPP2, KLK6). IPA identified disturbances in network functions associated with neurological disease, and development including cellular assembly and organization impacting on psychological disorders. Conclusions Our data in alcoholism support a reduction in expression of dlPFC mRNA for genes involved with neuronal growth, differentiation and signaling that targets white matter of the brain. PMID:24890784

  6. Neurophysiologic correlates of fMRI in human motor cortex.

    PubMed

    Hermes, Dora; Miller, Kai J; Vansteensel, Mariska J; Aarnoutse, Erik J; Leijten, Frans S S; Ramsey, Nick F

    2012-07-01

    The neurophysiological underpinnings of functional magnetic resonance imaging (fMRI) are not well understood. To understand the relationship between the fMRI blood oxygen level dependent (BOLD) signal and neurophysiology across large areas of cortex, we compared task related BOLD change during simple finger movement to brain surface electric potentials measured on a similar spatial scale using electrocorticography (ECoG). We found that spectral power increases in high frequencies (65-95 Hz), which have been related to local neuronal activity, colocalized with spatially focal BOLD peaks on primary sensorimotor areas. Independent of high frequencies, decreases in low frequency rhythms (<30 Hz), thought to reflect an aspect of cortical-subcortical interaction, colocalized with weaker BOLD signal increase. A spatial regression analysis showed that there was a direct correlation between the amplitude of the task induced BOLD change on different areas of primary sensorimotor cortex and the amplitude of the high frequency change. Low frequency change explained an additional, different part of the spatial BOLD variance. Together, these spectral power changes explained a significant 36% of the spatial variance in the BOLD signal change (R(2) = 0.36). These results suggest that BOLD signal change is largely induced by two separate neurophysiological mechanisms, one being spatially focal neuronal processing and the other spatially distributed low frequency rhythms. Copyright © 2011 Wiley-Liss, Inc.

  7. Hyperspectral optical tomography of intrinsic signals in the rat cortex

    PubMed Central

    Konecky, Soren D.; Wilson, Robert H.; Hagen, Nathan; Mazhar, Amaan; Tkaczyk, Tomasz S.; Frostig, Ron D.; Tromberg, Bruce J.

    2015-01-01

    Abstract. We introduce a tomographic approach for three-dimensional imaging of evoked hemodynamic activity, using broadband illumination and diffuse optical tomography (DOT) image reconstruction. Changes in diffuse reflectance in the rat somatosensory cortex due to stimulation of a single whisker were imaged at a frame rate of 5 Hz using a hyperspectral image mapping spectrometer. In each frame, images in 38 wavelength bands from 484 to 652 nm were acquired simultaneously. For data analysis, we developed a hyperspectral DOT algorithm that used the Rytov approximation to quantify changes in tissue concentration of oxyhemoglobin (ctHbO2) and deoxyhemoglobin (ctHb) in three dimensions. Using this algorithm, the maximum changes in ctHbO2 and ctHb were found to occur at 0.29±0.02 and 0.66±0.04  mm beneath the surface of the cortex, respectively. Rytov tomographic reconstructions revealed maximal spatially localized increases and decreases in ctHbO2 and ctHb of 321±53 and 555±96  nM, respectively, with these maximum changes occurring at 4±0.2  s poststimulus. The localized optical signals from the Rytov approximation were greater than those from modified Beer–Lambert, likely due in part to the inability of planar reflectance to account for partial volume effects. PMID:26835483

  8. Ventromedial prefrontal cortex and the regulation of physiological arousal

    PubMed Central

    Hu, Sien; Chao, Herta H.; Ide, Jaime S.; Luo, Xi; Farr, Olivia M.; Li, Chiang-shan R.

    2014-01-01

    Neuroimaging studies show a correlation between activity of the ventromedial prefrontal cortex (vmPFC) and skin conductance measurements. However, little is known whether this brain region plays a causal role in regulating physiological arousal. To address this question, we employed Granger causality analysis (GCA) to establish causality between cerebral blood oxygenation level-dependent and skin conductance signals in 24 healthy adults performing a cognitive task during functional magnetic resonance imaging. The results showed that activity of the vmPFC not only negatively correlated with skin conductance level (SCL) but also Granger caused SCL, thus establishing the direction of influence. Importantly, across participants, the strength of Granger causality was negatively correlated to phasic skin conductance responses elicited by external events during the behavioral task. In contrast, activity of the dorsal anterior cingulate cortex positively correlated with SCL but did not show a causal relationship in GCA. These new findings indicate that the vmPFC plays a causal role in regulating physiological arousal. Increased vmPFC activity leads to a decrease in skin conductance. The findings may also advance our understanding of dysfunctions of the vmPFC in mood and anxiety disorders that involve altered control of physiological arousal. PMID:23620600

  9. Background sounds contribute to spectrotemporal plasticity in primary auditory cortex.

    PubMed

    Moucha, Raluca; Pandya, Pritesh K; Engineer, Navzer D; Rathbun, Daniel L; Kilgard, Michael P

    2005-05-01

    The mammalian auditory system evolved to extract meaningful information from complex acoustic environments. Spectrotemporal selectivity of auditory neurons provides a potential mechanism to represent natural sounds. Experience-dependent plasticity mechanisms can remodel the spectrotemporal selectivity of neurons in primary auditory cortex (A1). Electrical stimulation of the cholinergic nucleus basalis (NB) enables plasticity in A1 that parallels natural learning and is specific to acoustic features associated with NB activity. In this study, we used NB stimulation to explore how cortical networks reorganize after experience with frequency-modulated (FM) sweeps, and how background stimuli contribute to spectrotemporal plasticity in rat auditory cortex. Pairing an 8-4 kHz FM sweep with NB stimulation 300 times per day for 20 days decreased tone thresholds, frequency selectivity, and response latency of A1 neurons in the region of the tonotopic map activated by the sound. In an attempt to modify neuronal response properties across all of A1 the same NB activation was paired in a second group of rats with five downward FM sweeps, each spanning a different octave. No changes in FM selectivity or receptive field (RF) structure were observed when the neural activation was distributed across the cortical surface. However, the addition of unpaired background sweeps of different rates or direction was sufficient to alter RF characteristics across the tonotopic map in a third group of rats. These results extend earlier observations that cortical neurons can develop stimulus specific plasticity and indicate that background conditions can strongly influence cortical plasticity.

  10. Dielectric elastomer energy harvesting undergoing polarization saturation

    NASA Astrophysics Data System (ADS)

    Liu, Liwu; Luo, Xiaojian; Liu, Yanju; Leng, Jinsong

    2012-04-01

    Mechanical energy can be converted into electrical energy by using a dielectric elastomer generator. The elastomer is susceptible to various models of failure, including electrical breakdown, electromechanical instability, loss of tension, and rupture by stretching. The models of failure define a cycle of maximal energy that can be converted. On the other hand, when subjected to voltage, the charge will be induced on a dielectric elastomer. When the voltage is small, the charge increases with the voltage. Along with the continuously increase of voltage, when the charge approaches a certain value, it would become saturated. This paper develops a thermodynamic model of dielectric elastomers undergoing polarization saturation. We studied the typical failure model with three variables of Gent Model silicone energy harvester and obtained an analytical solution of the constitutive equation of dielectric elastomer undergoing polarization saturation. These results can be used to facilitate the design and manufacture of dielectric elastomer energy harvesters.

  11. The effects of short-term enriched environment on capillaries of the middle-aged rat cortex.

    PubMed

    Qiu, Xuan; Li, Chen; Jiang, Rong; Chen, Lin; Huang, Chunxia; Yang, Shu; Lu, Wei; Shi, Xiaoyan; Zhao, Yuanyu; Gao, Yuan; Cheng, Guohua; Tang, Yong

    2011-11-14

    There has been no study investigating the effects of enriched environment on the capillaries of cortex with new stereological methods. In the present study, both 14 month female and male Sprague-Dawley rats were randomly divided into enriched environment (EE) rats and standard environment (SE) rats. EE rats were reared in enriched environment and SE rats were reared in standard environment for 4 months. The effects of short-term enriched environment on the cortex volume and on the total volume, total length, total surface area and mean diameter of the capillaries in the cortex of mid-aged Sprague-Dawley rats were quantitatively investigated with immunohistochemistry technique and unbiased stereological methods. There were no significant differences in the cortex volume, the total length and total surface area of the capillaries in the cortex between EE rats and SE rats. The total volume of the capillaries in the cortex of female EE rats and male EE rats was significantly increased when compared to female SE rats and male SE rats. The mean diameter of the capillaries in the cortex of female EE rats was significantly decreased when compared to that in female SE rats, but there was no significant difference in the mean diameter of the capillaries in the cortex between male EE rats and male SE rats. The present results indicate that enriched environment had a positive effect on the capillaries in the cortex of middle-aged rats. The present study might provide an important morphological basis for searching the ethology strategy to delay the progress of brain aging in the future.

  12. Sensorimotor organization in double cortex syndrome.

    PubMed

    Jirsch, Jeffrey D; Bernasconi, Neda; Villani, Flavio; Vitali, Paolo; Avanzini, Giuliano; Bernasconi, Andrea

    2006-06-01

    Subcortical band heterotopia is a diffuse malformation of cortical development related to pharmacologically intractable epilepsy. On magnetic resonance imaging (MRI), patients with "double cortex" syndrome (DCS) present with a band of heterotopic gray matter separated from the overlying cortex by a layer of white matter. The function and connectivity of the subcortical heterotopic band in humans is only partially understood. We studied six DCS patients with bilateral subcortical band heterotopias and six healthy controls using functional MRI (fMRI). In controls, simple motor task elicited contralateral activation of the primary motor cortex (M1) and ipsilateral activation of the cerebellum and left supplementary motor area (SMA). All DCS patients showed task-related contralateral activation of both M1 and the underlying heterotopic band. Ipsilateral motor activation was seen in 4/6 DCS patients. Furthermore, there were additional activations of nonprimary normotopic cortical areas. The sensory stimulus resulted in activation of the contralateral primary sensory cortex (SI) and the thalamus in all healthy subjects. The left sensory task also induced a contralateral activation of the insular cortex. Sensory activation of the contralateral SI was seen in all DCS patients and secondary somatosensory areas in 5/6. The heterotopic band beneath SI became activated in 3/6 DCS patients. Activations were also seen in subcortical structures for both paradigms. In DCS, motor and sensory tasks induce an activation of the subcortical heterotopic band. The recruitment of bilateral primary areas and higher-order association normotopic cortices indicates the need for a widespread network to perform simple tasks.

  13. [Raman spectra of monkey cerebral cortex tissue].

    PubMed

    Zhu, Ji-chun; Guo, Jian-yu; Cai, Wei-ying; Wang, Zu-geng; Sun, Zhen-rong

    2010-01-01

    Monkey cerebral cortex, an important part in the brain to control action and thought activities, is mainly composed of grey matter and nerve cell. In the present paper, the in situ Raman spectra of the cerebral cortex of the birth, teenage and aged monkeys were achieved for the first time. The results show that the Raman spectra for the different age monkey cerebral cortex exhibit most obvious changes in the regions of 1000-1400 and 2800-3000 cm(-1). With monkey growing up, the relative intensities of the Raman bands at 1313 and 2885 cm(-1) mainly assigned to CH2 chain vibrational mode of lipid become stronger and stronger whereas the relative intensities of the Raman bands at 1338 and 2932 cm(-1) mainly assigned to CH3 chain vibrational mode of protein become weaker and weaker. In addition, the two new Raman bands at 1296 and 2850 cm(-1) are only observed in the aged monkey cerebral cortex, therefore, the two bands can be considered as a character or "marker" to differentiate the caducity degree with monkey growth In order to further explore the changes, the relative intensity ratios of the Raman band at 1313 cm(-1) to that at 1338 cm(-1) and the Raman band at 2885 cm(-1) to that at 2 932 cm(-1), I1313/I1338 and I2885/I2932, which are the lipid-to-protein ratios, are introduced to denote the degree of the lipid content. The results show that the relative intensity ratios increase significantly with monkey growth, namely, the lipid content in the cerebral cortex increases greatly with monkey growth. So, the authors can deduce that the overmuch lipid is an important cause to induce the caducity. Therefore, the results will be a powerful assistance and valuable parameter to study the order of life growth and diagnose diseases.

  14. Cerebral Cortex Structure in Prodromal Huntington Disease

    PubMed Central

    Nopoulos, Peggy C.; Aylward, Elizabeth H.; Ross, Christopher A.; Johnson, Hans J.; Magnotta, Vincent A.; Juhl, Andrew R.; Pierson, Ronald K.; Mills, James; Langbehn, Douglas R.; Paulsen, Jane S.

    2010-01-01

    Neuroimaging studies of subjects who are gene-expanded for Huntington Disease, but not yet diagnosed (termed prodromal HD), report that the cortex is “spared,” despite the decrement in striatal and cerebral white-matter volume. Measurement of whole-cortex volume can mask more subtle, but potentially clinically relevant regional changes in volume, thinning, or surface area. The current study addressed this limitation by evaluating cortical morphology of 523 prodromal HD subjects. Participants included 693 individuals enrolled in the PREDICT-HD protocol. Of these participants, 523 carried the HD gene mutation (prodromal HD group); the remaining 170 were non gene-expanded and served as the comparison group. Based on age and CAG repeat length, gene-expanded subjects were categorized as “Far from onset,” “Midway to onset,” “Near onset,” and “already diagnosed.” MRI scans were processed using FreeSurfer. Cortical volume, thickness, and surface area were not significantly different between the Far from onset group and controls. However, beginning in the Midway to onset group, the cortex showed significant volume decrement, affecting most the posterior and superior cerebral regions. This pattern progressed when evaluating the groups further into the disease process. Areas that remained mostly unaffected included ventral and medial regions of the frontal and temporal cortex. Morphologic changes were mostly in thinning as surface area did not substantially change in most regions. Early in the course of HD, the cortex shows changes that are manifest as cortical thinning and are most robust in the posterior and superior regions of the cerebrum. PMID:20688164

  15. Coagulation management in patients undergoing neurosurgical procedures.

    PubMed

    Robba, Chiara; Bertuetti, Rita; Rasulo, Frank; Bertuccio, Alessando; Matta, Basil

    2017-10-01

    Management of coagulation in neurosurgical procedures is challenging. In this contest, it is imperative to avoid further intracranial bleeding. Perioperative bleeding can be associated with a number of factors, including anticoagulant drugs and coagulation status but is also linked to the characteristic and the site of the intracranial disorder. The aim of this review will be to focus primarily on the new evidence regarding the management of coagulation in patients undergoing craniotomy for neurosurgical procedures. Antihemostatic and anticoagulant drugs have shown to be associated with perioperative bleeding. On the other hand, an increased risk of venous thromboembolism and hypercoagulative state after elective and emergency neurosurgery, in particular after brain tumor surgery, has been described in several patients. To balance the risk between thrombosis and bleeding, it is important to be familiar with the perioperative changes in coagulation and with the recent management guidelines for anticoagulated patients undergoing neurosurgical procedures, in particular for those taking new direct anticoagulants. We have considered the current clinical trials and literature regarding both safety and efficacy of deep venous thrombosis prophylaxis in the neurosurgical population. These were mainly trials concerning both elective surgical and intensive care patients with a poor grade intracranial bleed or multiple traumas with an associated severe traumatic brain injury (TBI). Coagulation management remains a major issue in patients undergoing neurosurgical procedures. However, in this field of research, literature quality is poor and further studies are necessary to identify the best strategies to minimize risks in this group of patients.

  16. Preoperative Medical Testing in Medicare Patients Undergoing Cataract Surgery

    PubMed Central

    Chen, Catherine L.; Lin, Grace A.; Bardach, Naomi S.; Clay, Theodore H.; Boscardin, W. John; Gelb, Adrian W.; Maze, Mervyn; Gropper, Michael A.; Dudley, R. Adams

    2017-01-01

    BACKGROUND Routine preoperative testing is not recommended for patients undergoing cataract surgery, because testing neither decreases adverse events nor improves outcomes. We sought to assess adherence to this guideline, estimate expenditures from potentially unnecessary testing, and identify patient and health care system characteristics associated with potentially unnecessary testing. METHODS Using an observational cohort of Medicare beneficiaries undergoing cataract surgery in 2011, we determined the prevalence and cost of preoperative testing in the month before surgery. We compared the prevalence of preoperative testing and office visits with the mean percentage of beneficiaries who underwent tests and had office visits during the preceding 11 months. Using multivariate hierarchical analyses, we examined the relationship between preoperative testing and characteristics of patients, health system characteristics, surgical setting, care team, and occurrence of a preoperative office visit. RESULTS Of 440,857 patients, 53% had at least one preoperative test in the month before surgery. Expenditures on testing during that month were $4.8 million higher and expenditures on office visits $12.4 million higher (42% and 78% higher, respectively) than the mean monthly expenditures during the preceding 11 months. Testing varied widely among ophthalmologists; 36% of ophthalmologists ordered preoperative tests for more than 75% of their patients. A patient’s probability of undergoing testing was associated mainly with the ophthalmologist who managed the preoperative evaluation. CONCLUSIONS Preoperative testing before cataract surgery occurred frequently and was more strongly associated with provider practice patterns than with patient characteristics. (Funded by the Foundation for Anesthesia Education and Research and the Grove Foundation.) PMID:25875258

  17. 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.

  18. No evidence of somatotopic place of articulation feature mapping in motor cortex during passive speech perception.

    PubMed

    Arsenault, Jessica S; Buchsbaum, Bradley R

    2016-08-01

    The motor theory of speech perception has experienced a recent revival due to a number of studies implicating the motor system during speech perception. In a key study, Pulvermüller et al. (2006) showed that premotor/motor cortex differentially responds to the passive auditory perception of lip and tongue speech sounds. However, no study has yet attempted to replicate this important finding from nearly a decade ago. The objective of the current study was to replicate the principal finding of Pulvermüller et al. (2006) and generalize it to a larger set of speech tokens while applying a more powerful statistical approach using multivariate pattern analysis (MVPA). Participants performed an articulatory localizer as well as a speech perception task where they passively listened to a set of eight syllables while undergoing fMRI. Both univariate and multivariate analyses failed to find evidence for somatotopic coding in motor or premotor cortex during speech perception. Positive evidence for the null hypothesis was further confirmed by Bayesian analyses. Results consistently show that while the lip and tongue areas of the motor cortex are sensitive to movements of the articulators, they do not appear to preferentially respond to labial and alveolar speech sounds during passive speech perception.

  19. Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex.

    PubMed

    Rubino, Tiziana; Prini, Pamela; Piscitelli, Fabiana; Zamberletti, Erica; Trusel, Massimo; Melis, Miriam; Sagheddu, Claudia; Ligresti, Alessia; Tonini, Raffaella; Di Marzo, Vincenzo; Parolaro, Daniela

    2015-01-01

    Current concepts suggest that exposure to THC during adolescence may act as a risk factor for the development of psychiatric disorders later in life. However, the molecular underpinnings of this vulnerability are still poorly understood. To analyze this, we investigated whether and how THC exposure in female rats interferes with different maturational events occurring in the prefrontal cortex during adolescence through biochemical, pharmacological and electrophysiological means. We found that the endocannabinoid system undergoes maturational processes during adolescence and that THC exposure disrupts them, leading to impairment of both endocannabinoid signaling and endocannabinoid-mediated LTD in the adult prefrontal cortex. THC also altered the maturational fluctuations of NMDA subunits, leading to larger amounts of gluN2B at adulthood. Adult animals exposed to THC during adolescence also showed increased AMPA gluA1 with no changes in gluA2 subunits. Finally, adolescent THC exposure altered cognition at adulthood. All these effects seem to be triggered by the disruption of the physiological role played by the endocannabinoid system during adolescence. Indeed, blockade of CB1 receptors from early to late adolescence seems to prevent the occurrence of pruning at glutamatergic synapses. These results suggest that vulnerability of adolescent female rats to long-lasting THC adverse effects might partly reside in disruption of the pivotal role played by the endocannabinoid system in the prefrontal cortex maturation.

  20. Live Imaging of Primary Cerebral Cortex Cells Using a 2D Culture System.

    PubMed

    Landeira, Bruna Soares; Araújo, Jéssica Alves de Medeiros; Schroeder, Timm; Müller, Ulrich; Costa, Marcos R

    2017-08-09

    During cerebral cortex development, progenitor cells undergo several rounds of symmetric and asymmetric cell divisions to generate new progenitors or postmitotic neurons. Later, some progenitors switch to a gliogenic fate, adding to the astrocyte and oligodendrocyte populations. Using time-lapse video-microscopy of primary cerebral cortex cell cultures, it is possible to study the cellular and molecular mechanisms controlling the mode of cell division and cell cycle parameters of progenitor cells. Similarly, the fate of postmitotic cells can be examined using cell-specific fluorescent reporter proteins or post-imaging immunocytochemistry. More importantly, all these features can be analyzed at the single-cell level, allowing the identification of progenitors committed to the generation of specific cell types. Manipulation of gene expression can also be performed using viral-mediated transfection, allowing the study of cell-autonomous and non-cell-autonomous phenomena. Finally, the use of fusion fluorescent proteins allows the study of symmetric and asymmetric distribution of selected proteins during division and the correlation with daughter cells fate. Here, we describe the time-lapse video-microscopy method to image primary cerebral cortex murine cells for up to several days and analyze the mode of cell division, cell cycle length and fate of newly generated cells. We also describe a simple method to transfect progenitor cells, which can be applied to manipulate genes of interest or simply label cells with reporter proteins.

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

    PubMed

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

    2016-07-01

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

  2. Cholecystokinin from the entorhinal cortex enables neural plasticity in the auditory cortex.

    PubMed

    Li, Xiao; Yu, Kai; Zhang, Zicong; Sun, Wenjian; Yang, Zhou; Feng, Jingyu; Chen, Xi; Liu, Chun-Hua; Wang, Haitao; Guo, Yi Ping; He, Jufang

    2014-03-01

    Patients with damage to the medial temporal lobe show deficits in forming new declarative memories but can still recall older memories, suggesting that the medial temporal lobe is necessary for encoding memories in the neocortex. Here, we found that cortical projection neurons in the perirhinal and entorhinal cortices were mostly immunopositive for cholecystokinin (CCK). Local infusion of CCK in the auditory cortex of anesthetized rats induced plastic changes that enabled cortical neurons to potentiate their responses or to start responding to an auditory stimulus that was paired with a tone that robustly triggered action potentials. CCK infusion also enabled auditory neurons to start responding to a light stimulus that was paired with a noise burst. In vivo intracellular recordings in the auditory cortex showed that synaptic strength was potentiated after two pairings of presynaptic and postsynaptic activity in the presence of CCK. Infusion of a CCKB antagonist in the auditory cortex prevented the formation of a visuo-auditory association in awake rats. Finally, activation of the entorhinal cortex potentiated neuronal responses in the auditory cortex, which was suppressed by infusion of a CCKB antagonist. Together, these findings suggest that the medial temporal lobe influences neocortical plasticity via CCK-positive cortical projection neurons in the entorhinal cortex.

  3. GABAA receptor subunit gene expression in human prefrontal cortex: comparison of schizophrenics and controls

    NASA Technical Reports Server (NTRS)

    Akbarian, S.; Huntsman, M. M.; Kim, J. J.; Tafazzoli, A.; Potkin, S. G.; Bunney, W. E. Jr; Jones, E. G.; Bloom, F. E. (Principal Investigator)

    1995-01-01

    The prefrontal cortex of schizophrenics is hypoactive and displays changes related to inhibitory, GABAergic neurons, and GABAergic synapses. These changes include decreased levels of glutamic acid decarboxylase (GAD), the enzyme for GABA synthesis, upregulation of muscimol binding, and downregulation of benzodiazepine binding to GABAA receptors. Studies in the visual cortex of nonhuman primates have demonstrated that gene expression for GAD and for several GABAA receptor subunit polypeptides is under control of neuronal activity, raising the possibility that similar mechanisms in the hypoactive prefrontal cortex of schizophrenics may explain the abnormalities in GAD and in GABAA receptor regulation. In the present study, which is the first of its type on human cerebral cortex, levels of mRNAs for six GABAA receptor subunits (alpha 1, alpha 2, alpha 5, beta 1, beta 2, gamma 2) and their laminar expression patterns were analyzed in the prefrontal cortex of schizophrenics and matched controls, using in situ hybridization histochemistry and densitometry. Three types of laminar expression pattern were observed: mRNAs for the alpha 1, beta 2, and gamma 2 subunits, which are the predominant receptor subunits expressed in the mature cortex, were expressed at comparatively high levels by cells of all six cortical layers, but most intensely by cells in lower layer III and layer IV. mRNAs for the alpha 2, alpha 5, and beta 1 subunits were expressed at lower levels; alpha 2 and beta 1 were expressed predominantly by cells in layers II, III, and IV; alpha 5 was expressed predominantly in layers IV, V, and VI. There were no significant changes in overall mRNA levels for any of the receptor subunits in the prefrontal cortex of schizophrenics, and the laminar expression pattern of all six receptor subunit mRNAs did not differ between schizophrenics and controls. Because gene expression for GABAA receptor subunits is not consistently altered in the prefrontal cortex of

  4. 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

  5. GABAA receptor subunit gene expression in human prefrontal cortex: comparison of schizophrenics and controls

    NASA Technical Reports Server (NTRS)

    Akbarian, S.; Huntsman, M. M.; Kim, J. J.; Tafazzoli, A.; Potkin, S. G.; Bunney, W. E. Jr; Jones, E. G.; Bloom, F. E. (Principal Investigator)

    1995-01-01

    The prefrontal cortex of schizophrenics is hypoactive and displays changes related to inhibitory, GABAergic neurons, and GABAergic synapses. These changes include decreased levels of glutamic acid decarboxylase (GAD), the enzyme for GABA synthesis, upregulation of muscimol binding, and downregulation of benzodiazepine binding to GABAA receptors. Studies in the visual cortex of nonhuman primates have demonstrated that gene expression for GAD and for several GABAA receptor subunit polypeptides is under control of neuronal activity, raising the possibility that similar mechanisms in the hypoactive prefrontal cortex of schizophrenics may explain the abnormalities in GAD and in GABAA receptor regulation. In the present study, which is the first of its type on human cerebral cortex, levels of mRNAs for six GABAA receptor subunits (alpha 1, alpha 2, alpha 5, beta 1, beta 2, gamma 2) and their laminar expression patterns were analyzed in the prefrontal cortex of schizophrenics and matched controls, using in situ hybridization histochemistry and densitometry. Three types of laminar expression pattern were observed: mRNAs for the alpha 1, beta 2, and gamma 2 subunits, which are the predominant receptor subunits expressed in the mature cortex, were expressed at comparatively high levels by cells of all six cortical layers, but most intensely by cells in lower layer III and layer IV. mRNAs for the alpha 2, alpha 5, and beta 1 subunits were expressed at lower levels; alpha 2 and beta 1 were expressed predominantly by cells in layers II, III, and IV; alpha 5 was expressed predominantly in layers IV, V, and VI. There were no significant changes in overall mRNA levels for any of the receptor subunits in the prefrontal cortex of schizophrenics, and the laminar expression pattern of all six receptor subunit mRNAs did not differ between schizophrenics and controls. Because gene expression for GABAA receptor subunits is not consistently altered in the prefrontal cortex of

  6. Impairments of cingulated cortex in the generalized tonic-clonic seizure epilepsy by combining morphological and functional connectivity magnetic resonance imaging.

    PubMed

    Ke, Ming; Jin, Bixia; Liu, Guangyao; Yang, Xiaoping

    2017-01-01

    Previous studies suggested that the patients with generalized tonic-clonic seizure had structural abnormalities in the thalamus, cingulated cortex and some other specific brain regions. Concurrently, the abnormality in thalamocortical network and basal ganglia network has been found in idiopathic generalized epilepsy. The cingulated cortex, a nexus of information processing and regulation in human brain, is implicated in the propagation of generalized spike in IGE and the previous studies have suggested that the structural features and functional connectivity of the cingulated cortex have been changed. The aim of this study was to demonstrate the alterations in the cingulated cortex in generalized tonic-clonic seizure by combining morphological and functional connectivity magnetic resonance imaging. 19 patients with generalized tonic-clonic seizure and 19 age-and gender-matched healthy controls were involved in the study. The three-dimensional high-resolution T1-weighted magnetic resonance imaging data were acquired for voxel-based morphometry analysis, two-sample t-test run on the T1-weighted structural images revealed clusters exhibiting significant decreases in grey-matter volume in the generalized tonic-clonic seizure group, located within the cingulated cortex, thalamus, frontal lobe, temporal lobe, and cerebellum. The decreased gray matter volume in the cingulated cortex indicating that the cingulated cortex has structural impairments in generalized tonic-clonic seizure patients. The bilateral cingulated cortex, as detected with decreased gray matter volume in patients with generalized tonic-clonic seizure through voxel-based morphometry analysis, was selected as seed regions for functional connectivity analysis. Compared with controls, we found decreased functional connectivity to left anterior cingulated cortex (ROI1) in the cuneus, frontal lobe and precentral gyrus. There was no significant result when seeding at the right anterior cingulum gyrus (ROI2

  7. Cell Counts in Cerebral Cortex of an Autistic Patient.

    ERIC Educational Resources Information Center

    Coleman, Paul D.; And Others

    1985-01-01

    Numbers of neurons and glia were counted in the cerebral cortex of one case of autism and two age- and sex-matched controls. Cell counts were made in primary auditory cortex, Broca's speech area, and auditory association cortex. No consistent differences in cell density were found between brains of autistic and control patients. (Author/CL)

  8. A Functional Gradient in the Rodent Prefrontal Cortex Supports Behavioral Inhibition.

    PubMed

    Hardung, Stefanie; Epple, Robert; Jäckel, Zoe; Eriksson, David; Uran, Cem; Senn, Verena; Gibor, Lihi; Yizhar, Ofer; Diester, Ilka

    2017-02-20

    The ability to plan and execute appropriately timed responses to external stimuli is based on a well-orchestrated balance between movement initiation and inhibition. In impulse control disorders involving the prefrontal cortex (PFC) [1], this balance is disturbed, emphasizing the critical role that PFC plays in appropriately timing actions [2-4]. Here, we employed optogenetic and electrophysiological techniques to systematically analyze the functional role of five key subareas of the rat medial PFC (mPFC) and orbitofrontal cortex (OFC) in action control [5-9]. Inactivation of mPFC subareas induced drastic changes in performance, namely an increase (prelimbic cortex, PL) or decrease (infralimbic cortex, IL) of premature responses. Additionally, electrophysiology revealed a significant decrease in neuronal activity of a PL subpopulation prior to premature responses. In contrast, inhibition of OFC subareas (mainly the ventral OFC, i.e., VO) significantly impaired the ability to respond rapidly after external cues. Consistent with these findings, mPFC activity during response preparation predicted trial outcomes and reaction times significantly better than OFC activity. These data support the concept of opposing roles of IL and PL in directing proactive behavior and argue for an involvement of OFC in predominantly reactive movement control. By attributing defined roles to rodent PFC sections, this study contributes to a deeper understanding of the functional heterogeneity of this brain area and thus may guide medically relevant studies of PFC-associated impulse control disorders in this animal model for neural disorders [10-12].

  9. [Significance and expression of FKHR and AKT after subarachnoid hemorrhage in rat brain cortex].

    PubMed

    Miao, Chun-ming; Luo, Qi; Wang, Wei-wei; Kang, Jin-song; Shi, Guo-ying; Li, Hong-yan; Zhang, Yong

    2010-06-01

    To study the significance and expression of FKHR and AKT after subarachnoid hemorrhage (SAH) in rat brain cortex. Twenty-four rats were randomly divided into three groups: sham, SAH and SAH plus nimodipine (n=8 each). A reliable SAH model was established by double injections of blood into cistern magna in Wistar rats. The neurological scores were measured by Loeffler and the expressions of FKHR, P-FKHR, AKT and P-FKHR detected by Western blot. Compared with sham group, the neurological score of SAH group obviously decreased (P < 0.05), the expression of FKHR became elevated in rat cortex (P < 0.01), the expression of AKT had no change and the expressions of P-AKT and P-FKHR obviously decreased (all P < 0.01). But the neurological score markedly increased (P < 0.01) and the expressions of P-AKT and P-FKHR became elevated (all P < 0.01) after administration of nimodipine. Both P-AKT and P-FKHR are involved in the process of brain cortex damage induced by SAH. The protective effects of nimodipine on brain injury induced by SAH may be related to the elevated expressions of P-AKT and P-FKHR in brain cortex.

  10. Developmental role of the cell adhesion molecule Contactin-6 in the cerebral cortex and hippocampus

    PubMed Central

    Zuko, Amila; Oguro-Ando, Asami; van Dijk, Roland; Gregorio-Jordan, Sara; van der Zwaag, Bert; Burbach, J. Peter H.

    2016-01-01

    ABSTRACT The gene encoding the neural cell adhesion molecule Contactin-6 (Cntn6 a.k.a. NB-3) has been implicated as an autism risk gene, suggesting that its mutation is deleterious to brain development. Due to its GPI-anchor at Cntn6 may exert cell adhesion/receptor functions in complex with other membrane proteins, or serve as a ligand. We aimed to uncover novel phenotypes related to Cntn6 functions during development in the cerebral cortex of adult Cntn6−/− mice. We first determined Cntn6 protein and mRNA expression in the cortex, thalamic nuclei and the hippocampus at P14, which decreased specifically in the cortex at adult stages. Neuroanatomical analysis demonstrated a significant decrease of Cux1+ projection neurons in layers II-IV and an increase of FoxP2+ projection neurons in layer VI in the visual cortex of adult Cntn6−/− mice compared to wild-type controls. Furthermore, the number of parvalbumin+ (PV) interneurons was decreased in Cntn6−/− mice, while the amount of NPY+ interneurons remained unchanged. In the hippocampus the delineation and outgrowth of mossy fibers remained largely unchanged, except for the observation of a larger suprapyramidal bundle. The observed abnormalities in the cerebral cortex and hippocampus of Cntn6−/− mice suggests that Cntn6 serves developmental functions involving cell survival, migration and fasciculation. Furthermore, these data suggest that Cntn6 engages in both trans- and cis-interactions and may be involved in larger protein interaction networks. PMID:26939565

  11. [Eradication of Staphylococcus aureus in carrier patients undergoing joint arthroplasty].

    PubMed

    Barbero Allende, José M; Romanyk Cabrera, Juan; Montero Ruiz, Eduardo; Vallés Purroy, Alfonso; Melgar Molero, Virginia; Agudo López, Rosa; Gete García, Luis; López Álvarez, Joaquín

    2015-02-01

    Prosthetic joint infection (PJI) is a complication with serious repercussions and its main cause is Staphylococcus aureus. The purpose of this study is to determine whether decolonization of S.aureus carriers helps to reduce the incidence of PJI by S.aureus. An S.aureus screening test was performed on nasal carriers in patients undergoing knee or hip arthroplasty between January and December 2011. Patients with a positive test were treated with intranasal mupirocin and chlorhexidine soap 5 days. The incidence of PJI was compared with patients undergoing the same surgery between January and December 2010. A total of 393 joint replacements were performed in 391 patients from the control group, with 416 joint replacements being performed in the intervention group. Colonization study was performed in 382 patients (91.8%), of which 102 were positive (26.7%) and treated. There was 2 PJI due S.aureus compared with 9 in the control group (0.5% vs 2.3%, odds ratio [OR]: 0.2, 95% confidence interval [CI]: 0.4 to 2.3, P=.04). In our study, the detection of colonization and eradication of S.aureus carriers achieved a significant decrease in PJI due to S.aureus compared to a historical group. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  12. Altered Processing of Amyloid Precursor Protein in Cells Undergoing Apoptosis

    PubMed Central

    Fiorelli, Tina; Kirouac, Lisa; Padmanabhan, Jaya

    2013-01-01

    Altered proteolysis of amyloid precursor protein is an important determinant of pathology development in Alzheimer's disease. Here, we describe the detection of two novel fragments of amyloid precursor protein in H4 neuroglioma cells undergoing apoptosis. Immunoreactivity of these 25–35 kDa fragments to two different amyloid precursor protein antibodies suggests that they contain the amyloid-β region and an epitope near the C-terminus of amyloid precursor protein. Generation of these fragments is associated with cleavage of caspase-3 and caspase-7, suggesting activation of these caspases. Studies in neurons undergoing DNA damage-induced apoptosis also showed similar results. Inclusion of caspase inhibitors prevented the generation of these novel fragments, suggesting that they are generated by a caspase-dependent mechanism. Molecular weight prediction and immunoreactivity of the fragments generated suggested that such fragments could not be generated by cleavage at any previously identified caspase, secretase, or calpain site on amyloid precursor protein. Bioinformatic analysis of the amino acid sequence of amyloid precursor protein revealed that fragments fitting the observed size and immunoreactivity could be generated by either cleavage at a novel, hitherto unidentified, caspase site or at a previously identified matrix metalloproteinase site in the extracellular domain. Proteolytic cleavage at any of these sites leads to a decrease in the generation of α-secretase cleaved secreted APP, which has both anti-apoptotic and neuroprotective properties, and thus may contribute to neurodegeneration in Alzheimer's disease. PMID:23469123

  13. [Has ketamine preemptive analgesic effect in patients undergoing abdominal hysterectomy?].

    PubMed

    Karaman, Semra; Kocabaş, Seden; Zincircioğlu, Ciler; Firat, Vicdan

    2006-07-01

    The aim of this study was to determine if preemptive use of the NMDA receptor antogonist ketamine decreases postoperative pain in patients undergoing abdominal hystrectomy. A total of 60 patients admitted for total abdominal hysterectomy were included in this study after the approval of the ethic committee, and the patients were randomly classified into three groups. After standart general anaesthesia, before or after incision patients received bolus saline or ketamine. Group S received only saline while Group Kpre received ketamine 0.4 mg/kg before incision and saline after incision, and Group Kpost received saline before incision and 0.4 mg/kg ketamine after incision. Postoperatif analgesia was maintained with i.v. PCA morphine. Pain scores were assessed with Vizüal Analog Scale (VAS), Verbal Rating Scale (VRS) at 1., 2, 3., 4., 8., 12. ve 24. hours postoperatively. First analgesic requirement time, morphine consumption and side effects were recorded. There were no significant differences between groups with respect to VAS / VRS scores, the time for first analgesic dose, and morphine consumption ( p>0.05). Patients in Group S had significantly lower sedation scores than either of the ketamine treated groups ( p<0.05). In conclusion, a single dose of ketamin had no preemptive analgesic effect in patients undergoing abdominal hysterectomy, but further investigation is needed for different operation types and dose regimens.

  14. Clemastine Enhances Myelination in the Prefrontal Cortex and Rescues Behavioral Changes in Socially Isolated Mice

    PubMed Central

    Dupree, Jeffrey L.; Gacias, Mar; Frawley, Rebecca; Sikder, Tamjeed; Naik, Payal; Casaccia, Patrizia

    2016-01-01

    Altered myelin structure and oligodendrocyte function have been shown to correlate with cognitive and motor dysfunction and deficits in social behavior. We and others have previously demonstrated that social isolation in mice induced behavioral, transcriptional, and ultrastructural changes in oligodendrocytes of the prefrontal cortex (PFC). However, whether enhancing myelination and oligodendrocyte differentiation could be beneficial in reversing such changes remains unexplored. To test this hypothesis, we orally administered clemastine, an antimuscarinic compound that has been shown to enhance oligodendrocyte differentiation and myelination in vitro, for 2 weeks in adult mice following social isolation. Clemastine successfully reversed social avoidance behavior in mice undergoing prolonged social isolation. Impaired myelination was rescued by oral clemastine treatment, and was associated with enhanced oligodendrocyte progenitor differentiation and epigenetic changes. Clemastine induced higher levels of repressive histone methylation (H3K9me3), a marker for heterochromatin, in oligodendrocytes, but not neurons, of the PFC. This was consistent with the capability of clemastine in elevating H3K9 histone methyltransferases activity in cultured primary mouse oligodendrocytes, an effect that could be antagonized by cotreatment with muscarine. Our data suggest that promoting adult myelination is a potential strategy for reversing depressive-like social behavior. SIGNIFICANCE STATEMENT Oligodendrocyte development and myelination are highly dynamic processes influenced by experience and neuronal activity. However, whether enhancing myelination and oligodendrocyte differentiation is beneficial to treat depressive-like behavior has been unexplored. Mice undergoing prolonged social isolation display impaired myelination in the prefrontal cortex. Clemastine, a Food and Drug Administration-approved antimuscarinic compound that has been shown to enhance myelination under

  15. Transient contribution of left posterior parietal cortex to cognitive restructuring

    PubMed Central

    Sutoh, Chihiro; Matsuzawa, Daisuke; Hirano, Yoshiyuki; Yamada, Makiko; Nagaoka, Sawako; Chakraborty, Sudesna; Ishii, Daisuke; Matsuda, Shingo; Tomizawa, Haruna; Ito, Hiroshi; Tsuji, Hiroshi; Obata, Takayuki; Shimizu, Eiji

    2015-01-01

    Cognitive restructuring is a fundamental method within cognitive behavioural therapy of changing dysfunctional beliefs into flexible beliefs and learning to react appropriately to the reality of an anxiety-causing situation. To clarify the neural mechanisms of cognitive restructuring, we designed a unique task that replicated psychotherapy during a brain scan. The brain activities of healthy male participants were analysed using functional magnetic resonance imaging. During the brain scan, participants underwent Socratic questioning aimed at cognitive restructuring regarding the necessity of handwashing after using the restroom. The behavioural result indicated that the Socratic questioning effectively decreased the participants' degree of belief (DOB) that they must wash their hands. Alterations in the DOB showed a positive correlation with activity in the left posterior parietal cortex (PPC) while the subject thought about and rated own belief. The involvement of the left PPC not only in planning and decision-making but also in conceptualization may play a pivotal role in cognitive restructuring. PMID:25775998

  16. Microglia contact induces synapse formation in developing somatosensory cortex

    PubMed Central

    Miyamoto, Akiko; Wake, Hiroaki; Ishikawa, Ayako Wendy; Eto, Kei; Shibata, Keisuke; Murakoshi, Hideji; Koizumi, Schuichi; Moorhouse, Andrew J.; Yoshimura, Yumiko; Nabekura, Junichi

    2016-01-01

    Microglia are the immune cells of the central nervous system that play important roles in brain pathologies. Microglia also help shape neuronal circuits during development, via phagocytosing weak synapses and regulating neurogenesis. Using in vivo multiphoton imaging of layer 2/3 pyramidal neurons in the developing somatosensory cortex, we demonstrate here that microglial contact with dendrites directly induces filopodia formation. This filopodia formation occurs only around postnatal day 8–10, a period of intense synaptogenesis and when microglia have an activated phenotype. Filopodia formation is preceded by contact-induced Ca2+ transients and actin accumulation. Inhibition of microglia by genetic ablation decreases subsequent spine density, functional excitatory synapses and reduces the relative connectivity from layer 4 neurons. Our data provide the direct demonstration of microglial-induced spine formation and provide further insights into immune system regulation of neuronal circuit development, with potential implications for developmental disorders of immune and brain dysfunction. PMID:27558646

  17. Perirhinal Cortex Hyperexcitability in Pilocarpine-Treated Epileptic Rats

    PubMed Central

    Benini, Ruba; Longo, Daniela; Biagini, Giuseppe; Avoli, Massimo

    2016-01-01

    The perirhinal cortex (PC), which is heavily connected with several epileptogenic regions of the limbic system such as the entorhinal cortex and amygdala, is involved in the generation and spread of seizures. However, the functional alterations occurring within an epileptic PC network are unknown. Here, we analyzed this issue by using in vitro electrophysiology and immunohistochemistry in brain tissue obtained from pilocarpine-treated epileptic rats and age-matched, nonepileptic controls (NECs). Neurons recorded intracellularly from the PC deep layers in the two experimental groups had similar intrinsic and firing properties and generated spontaneous depolarizing and hyperpolarizing postsynaptic potentials with comparable duration and amplitude. However, spontaneous and stimulus-induced epileptiform discharges were seen with field potential recordings in over one-fifth of pilocarpine-treated slices but never in NEC tissue. These network events were reduced in duration by antagonizing NMDA receptors and abolished by NMDA + non-NMDA glutamatergic receptor antagonists. Pharmacologically isolated isolated inhibitory postsynaptic potentials had reversal potentials for the early GABAA receptor-mediated component that were significantly more depolarized in pilocarpine-treated cells. Experiments with a potassium-chloride cotransporter 2 antibody identified, in pilocarpine-treated PC, a significant immunostaining decrease that could not be explained by neuronal loss. However, interneurons expressing parvalbumin and neuropeptide Y were found to be decreased throughout the PC, whereas cholecystokinin-positive cells were diminished in superficial layers. These findings demonstrate synaptic hyper-excitability that is contributed by attenuated inhibition in the PC of pilocarpine-treated epileptic rats and underscore the role of PC networks in temporal lobe epilepsy. PMID:20865722

  18. [Hyperkalemia after arterial revascularization in a patient undergoing arm replantation].

    PubMed

    Imanaka, Norie; Nakasuji, Masato; Nomura, Masataka; Yoshioka, Miwako; Miyata, Taeko; Tanaka, Masuji

    2014-12-01

    A 25-year-old man was admitted for arm replantation. His left upper arm was completely amputated by conveyer belt Anesthesia was induced with propofol (80 mg), rocuronium (50 mg), remifentanil (0.15 μg x kg(-1) x min(-1)) and maintained with sevoflurane (1-2%) and remifentanil (0.1-0.3 μg x kg(-1) x min(-1)). The plastic surgeons revascularized subclavian artery quickly but blood pressure decreased to 40-50 mmHg because of massive bleeding and plasma potassium concentration reached 5.8 mEq x l(-1). Noradrenaline (0.3 μg x kg(-1) x min(-1)) and massive albumin on behalf of red blood cells were administered. After we treated hyperkalemia and hypotension, the subclavian vein was successfully revascularized. We should maintain low potassium concentration before revascularization in patients undergoing arm replantation.

  19. Task-relevancy effects on movement-related gating are modulated by continuous theta-burst stimulation of the dorsolateral prefrontal cortex and primary somatosensory cortex.

    PubMed

    Brown, Katlyn E; Ferris, Jennifer K; Amanian, Mohammad A; Staines, W Richard; Boyd, Lara A

    2015-03-01

    Movement-related gating ensures that decreased somatosensory information from external stimulation reaches the cortex during movement when compared to resting levels; however, gating may be influenced by task-relevant manipulations, such that increased sensory information ascends to the cortex when information is relevant to goal-based actions. These task-relevancy effects are hypothesized to be controlled by a network involving the dorsolateral prefrontal cortex (DLPFC) based on this region's known role in selective attention, modulating the primary somatosensory cortex (S1). The purpose of the current study was first to verify task-relevancy influences on movement-related gating in the upper limb, and second to test the contribution of the DLPFC and the primary somatosensory cortex (S1) to these relevancy effects. Ten healthy participants received median nerve stimulation at the left wrist during three conditions: rest, task-irrelevant movement, and task-relevant movement. Cortical responses to median nerve stimulations were measured in the form of somatosensory evoked potentials (SEPs). The three conditions were collected on a baseline day and on two separate days following continuous theta-burst (cTBS), which transiently reduces cortical excitability, over either the contralateral S1 or DLPFC. Results demonstrated a significant interaction between stimulation and condition, with a priori contrasts revealing that cTBS over either S1 or DLPFC diminished the relevancy-based modulation of SEP amplitudes; however, the degree of this effect was different. These results indicate that DLPFC influences over S1 are involved in the facilitation of relevant sensory information during movement.

  20. Visual cortex in aging and Alzheimer's disease: changes in visual field maps and population receptive fields

    PubMed Central

    Brewer, Alyssa A.; Barton, Brian

    2012-01-01

    Although several studies have suggested that cortical alterations underlie such age-related visual deficits as decreased acuity, little is known about what changes actually occur in visual cortex during healthy aging. Two recent studies showed changes in primary visual cortex (V1) during normal aging; however, no studies have characterized the effects of aging on visual cortex beyond V1, important measurements both for understanding the aging process and for comparison to changes in age-related diseases. Similarly, there is almost no information about changes in visual cortex in Alzheimer's disease (AD), the most common form of dementia. Because visual deficits are often reported as one of the first symptoms of AD, measurements of such changes in the visual cortex of AD patients might improve our understanding of how the visual system is affected by neurodegeneration as well as aid early detection, accurate diagnosis and timely treatment of AD. Here we use fMRI to first compare the visual field map (VFM) organization and population receptive fields (pRFs) between young adults and healthy aging subjects for occipital VFMs V1, V2, V3, and hV4. Healthy aging subjects do not show major VFM organizational deficits, but do have reduced surface area and increased pRF sizes in the foveal representations of V1, V2, and hV4 relative to healthy young control subjects. These measurements are consistent with behavioral deficits seen in healthy aging. We then demonstrate the feasibility and first characterization of these measurements in two patients with mild AD, which reveal potential changes in visual cortex as part of the pathophysiology of AD. Our data aid in our understanding of the changes in the visual processing pathways in normal aging and provide the foundation for future research into earlier and more definitive detection of AD. PMID:24570669

  1. Coumarin effects on amino acid levels in mice prefrontal cortex and hippocampus.

    PubMed

    Pereira, Elaine Cristina; Lucetti, Daniel Luna; Barbosa-Filho, José Maria; de Brito, Eliane Magalhães; Monteiro, Valdécio Silvano; Patrocínio, Manoel Cláudio Azevedo; de Moura, Rebeca Ribeiro; Leal, Luzia Kalyne Almeida Moreira; Macedo, Danielle Silveira; de Sousa, Francisca Cléa Florenço; de Barros Viana, Glauce Socorro; Vasconcelos, Silvânia Maria Mendes

    2009-04-24

    Coumarin is a compound known to be present in a wide variety of plants, microorganisms and animal species. Most of its effects were studied in organs and systems other than the central nervous system. The present work evaluated the effect of coumarin administration on the levels of gamma-aminobutyric acid (GABA), glutamate (GLU), glycine (GLY) and taurine (TAU) in the prefrontal cortex and hippocampus of mice. Male Swiss mice were treated with distilled water (controls), coumarin (20 or 40 mg/kg, i.p.) or diazepam (1 mg/kg, i.p.). Results showed that in the prefrontal cortex, coumarin at the lowest dose increased the levels of GLU and TAU, while GABA increased with both doses studied and GLY had its levels increased only at the dose of 40 mg/kg. Diazepam (DZP) increased the levels of GABA and TAU and decreased the levels of GLU and GLY in this area. In the hippocampus, only glutamate had its levels decreased after coumarin treatment, while diazepam increased the levels of GABA and TAU and decreased the levels of GLU in this brain region. We concluded that coumarin stimulates the release of endogenous amino acids, increasing the levels of inhibitory and excitatory amino acids in the prefrontal cortex, and decreasing glutamate levels in the hippocampus. Together, these results are of interest, considering that some neurodegenerative diseases and seizures are related to the imbalance of the amino acid levels in the CNS suggesting a perspective of a therapeutic use of coumarins in these disorders.

  2. Reconstructing Speech from Human Auditory Cortex

    PubMed Central

    Pasley, Brian N.; David, Stephen V.; Mesgarani, Nima; Flinker, Adeen; Shamma, Shihab A.; Crone, Nathan E.; Knight, Robert T.; Chang, Edward F.

    2012-01-01

    How the human auditory system extracts perceptually relevant acoustic features of speech is unknown. To address this question, we used intracranial recordings from nonprimary auditory cortex in the human superior temporal gyrus to determine what acoustic information in speech sounds can be reconstructed from population neural activity. We found that slow and intermediate temporal fluctuations, such as those corresponding to syllable rate, were accurately reconstructed using a linear model based on the auditory spectrogram. However, reconstruction of fast temporal fluctuations, such as syllable onsets and offsets, required a nonlinear sound representation based on temporal modulation energy. Reconstruction accuracy was highest within the range of spectro-temporal fluctuations that have been found to be critical for speech intelligibility. The decoded speech representations allowed readout and identification of individual words directly from brain activity during single trial sound presentations. These findings reveal neural encoding mechanisms of speech acoustic parameters in higher order human auditory cortex. PMID:22303281

  3. Reconstructing speech from human auditory cortex.

    PubMed

    Pasley, Brian N; David, Stephen V; Mesgarani, Nima; Flinker, Adeen; Shamma, Shihab A; Crone, Nathan E; Knight, Robert T; Chang, Edward F

    2012-01-01

    How the human auditory system extracts perceptually relevant acoustic features of speech is unknown. To address this question, we used intracranial recordings from nonprimary auditory cortex in the human superior temporal gyrus to determine what acoustic information in speech sounds can be reconstructed from population neural activity. We found that slow and intermediate temporal fluctuations, such as those corresponding to syllable rate, were accurately reconstructed using a linear model based on the auditory spectrogram. However, reconstruction of fast temporal fluctuations, such as syllable onsets and offsets, required a nonlinear sound representation based on temporal modulation energy. Reconstruction accuracy was highest within the range of spectro-temporal fluctuations that have been found to be critical for speech intelligibility. The decoded speech representations allowed readout and identification of individual words directly from brain activity during single trial sound presentations. These findings reveal neural encoding mechanisms of speech acoustic parameter