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  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 Central

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

    2015-01-01

    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. PMID:25480358

  3. 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.

  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. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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).

  3. 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.

  4. 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.

  5. Damage to temporo-parietal cortex decreases incidental activation of thematic relations during spoken word comprehension.

    PubMed

    Mirman, Daniel; Graziano, Kristen M

    2012-07-01

    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 examine incidental activation of taxonomic and thematic relations during spoken word comprehension in participants with aphasia. Three groups of participants were tested: neurologically intact control participants (N=14), individuals with aphasia resulting from lesions in left hemisphere BA 39 and surrounding temporo-parietal cortex regions (N=7), and individuals with the same degree of aphasia severity and semantic impairment and anterior left hemisphere lesions (primarily inferior frontal gyrus and anterior temporal lobe) that spared BA 39 (N=6). The posterior lesion group showed reduced and delayed activation of thematic relations, but not taxonomic relations. In contrast, the anterior lesion group exhibited longer-lasting activation of taxonomic relations and did not differ from control participants in terms of activation of thematic relations. These results suggest that taxonomic and thematic semantic knowledge are functionally and neuroanatomically distinct, with the temporo-parietal cortex playing a particularly important role in thematic semantics.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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.

  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. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. Cytoarchitecture-Dependent Decrease in Propagation Velocity of Cortical Spreading Depression in the Rat Insular Cortex Revealed by Optical Imaging.

    PubMed

    Fujita, Satoshi; Mizoguchi, Naoko; Aoki, Ryuhei; Cui, Yilong; Koshikawa, Noriaki; Kobayashi, Masayuki

    2016-04-01

    Cortical spreading depression (SD) is a self-propagating wave of depolarization accompanied by a substantial disturbance of the ionic distribution between the intra- and extracellular compartments. Glial cells, including astrocytes, play critical roles in maintenance of the extracellular environment, including ionic distribution. Therefore, SD propagation in the cerebral cortex may depend on the density of astrocytes. The present study aimed to examine the profile of SD propagation in the insular cortex (IC), which is located between the neocortex and paleocortex and is where the density of astrocytes gradually changes. The velocity of SD propagation in the neocortex, including the somatosensory, motor, and granular insular cortices (5.7 mm/min), was higher than that (2.8 mm/min) in the paleocortex (agranular insular and piriform cortices). Around thick vessels, including the middle cerebral artery, SD propagation was frequently delayed and sometimes disappeared. Immunohistological analysis of glial fibrillary acidic protein (GFAP) demonstrated the sparse distribution of astrocytes in the somatosensory cortex and the IC dorsal to the rhinal fissure, whereas the ventral IC showed a higher density of astrocytes. These results suggest that cortical cytoarchitectonic features, which possibly involve the distribution of astrocytes, are crucial for regulating the velocity of SD propagation in the cerebral cortex.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  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. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

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

    PubMed

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

    2015-10-15

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

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. The relationship between brain cortical activity and brain oxygenation in the prefrontal cortex during hypergravity exposure.

    PubMed

    Smith, Craig; Goswami, Nandu; Robinson, Ryan; von der Wiesche, Melanie; Schneider, Stefan

    2013-04-01

    Artificial gravity has been proposed as a method to counteract the physiological deconditioning of long-duration spaceflight; however, the effects of hypergravity on the central nervous system has had little study. The study aims to investigate whether there is a relationship between prefrontal cortex brain activity and prefrontal cortex oxygenation during exposure to hypergravity. Twelve healthy participants were selected to undergo hypergravity exposure aboard a short-arm human centrifuge. Participants were exposed to hypergravity in the +Gz axis, starting from 0.6 +Gz for women, and 0.8 +Gz for men, and gradually increasing by 0.1 +Gz until the participant showed signs of syncope. Brain cortical activity was measured using electroencephalography (EEG) and localized to the prefrontal cortex using standard low-resolution brain electromagnetic tomography (LORETA). Prefrontal cortex oxygenation was measured using near-infrared spectroscopy (NIRS). A significant increase in prefrontal cortex activity (P < 0.05) was observed during hypergravity exposure compared with baseline. Prefrontal cortex oxygenation was significantly decreased during hypergravity exposure, with a decrease in oxyhemoglobin levels (P < 0.05) compared with baseline and an increase in deoxyhemoglobin levels (P < 0.05) with increasing +Gz level. No significant correlation was found between prefrontal cortex activity and oxy-/deoxyhemoglobin. It is concluded that the increase in prefrontal cortex activity observed during hypergravity was most likely not the result of increased +Gz values resulting in a decreased oxygenation produced through hypergravity exposure. No significant relationship between prefrontal cortex activity and oxygenation measured by NIRS concludes that brain activity during exposure to hypergravity may be difficult to measure using NIRS. Instead, the increase in prefrontal cortex activity might be attributable to psychological stress, which could pose a problem for the use of a

  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

    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

  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. 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

  6. 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.

  7. 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.

  8. 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.

  9. Appetite - decreased

    MedlinePlus

    ... cancer Ovarian cancer Stomach cancer Pancreatic cancer Other causes of decreased appetite include: Chronic liver disease Chronic kidney disease Chronic obstructive pulmonary disease (COPD) Dementia Heart failure ...

  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. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. [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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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…

  9. Remodeling of the piriform cortex after lesion in adult rodents.

    PubMed

    Rossi, Sharyn L; Mahairaki, Vasiliki; Zhou, Lijun; Song, Yeajin; Koliatsos, Vassilis E

    2014-09-10

    Denervation of the piriform cortex by bulbotomy causes a series of important cellular changes in the inhibitory interneurons of layer I and transsynaptic apoptosis of a large number of pyramidal neurons in outer layer II within 24 h. In this study, we report that following the marked loss of neurons in outer layer II, the piriform cortex is reconstituted by the addition of newly formed neurons that restore the number to a preinjury level within 30 days. We provide evidence that the number of newly divided neuronal progenitors increases after injury and further show that a population of doublecortin-positive cells that resides in the piriform cortex decreases after injury. Taken together, these findings suggest that the piriform cortex has significant neurogenic potential that is activated following sensory denervation and may contribute toward the replacement of neurons in outer layer II.

  10. 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

  11. 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.

  12. 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.

  13. 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…

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. Electrocorticography Reveals Enhanced Visual Cortex Responses to Visual Speech

    PubMed Central

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

    2015-01-01

    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. PMID:24904069

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

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

    DTIC Science & Technology

    2013-01-01

    a study of combat casualties in an emergency department in Iraq. Electrocardiograms of 70 acutely injured adults were recorded. Twelve underwent LSIs...and 50 milliseconds, square root of the mean of the squares of differences between adjacent NN intervals) were computed. Results: Differences in mean HR...2.48; P b .001) differed significantly. Conclusions: Complexity of HR dynamics over a range of time scales was lower in high risk than in low risk combat

  12. [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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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…

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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…

  7. 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.

  8. 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…

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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.

  6. Entorhinal cortex stimulation modulates amygdala and piriform cortex responses to olfactory bulb inputs in the rat.

    PubMed

    Mouly, A-M; Di Scala, G

    2006-01-01

    The rodent olfactory bulb sends direct projections to the piriform cortex and to two structures intimately implicated in memory processes, the entorhinal cortex and the amygdala. The piriform cortex has monosynaptic projections with the amygdala and the piriform cortex and is therefore in a position to modulate olfactory input either directly in the piriform cortex, or via the amygdala. In order to investigate this hypothesis, field potential signals induced in anesthetized rats by electrical stimulation of the olfactory bulb or the entorhinal cortex were recorded simultaneously in the piriform cortex (anterior part and posterior part) and the amygdala (basolateral nucleus and cortical nucleus). Single-site paired-pulse stimulation was used to assess the time courses of short-term inhibition and facilitation in each recording site in response to electrical stimulation of the olfactory bulb and entorhinal cortex. Paired-pulse stimulation of the olfactory bulb induced homosynaptic inhibition for short interpulse interpulse intervals (20-30 ms) in all the recording sites, with a significantly lower degree of inhibition in the anterior piriform cortex than in the other structures. At longer intervals (40-80 ms), paired-pulse facilitation was observed in all the structures. Paired-pulse stimulation of the entorhinal cortex mainly resulted in inhibition for the shortest interval duration (20 ms) in anterior piriform cortex, posterior piriform cortex and amygdala basolateral but not cortical nucleus. Double-site paired-pulse stimulation was then applied to determine if stimulation of the entorhinal cortex can modulate responses to olfactory bulb stimulation. For short interpulse intervals (20 ms) heterosynaptic inhibition was observed in anterior piriform cortex, posterior piriform cortex and amygdala basolateral but not cortical nucleus. The level of inhibition was greater in the basolateral nucleus than in the other structures. Taken together these data suggest that the

  7. Preparatory attention in visual cortex.

    PubMed

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

    2017-03-02

    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.

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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…

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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…

  5. 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.

  6. 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

  7. 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)

  8. 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

  9. 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

  10. [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.

  11. Viscoelastic behavior of polymers undergoing crosslinking reactions.

    NASA Technical Reports Server (NTRS)

    Moacanin, J.; Aklonis, J. J.

    1971-01-01

    Previously a method was developed for predicting the viscoelastic response of polymers undergoing scission reactions. These results are now extended to include crosslinking reactions. As for scission, at any given time the character of the network chains is determined by the instantaneous crosslink density. For scission all chains were assumed to carry the same stress; for crosslinking, however, the stress is distributed between the 'new' and 'old' chains. Equations for calculating the creep response of a system which experiences a step increase in crosslink density are derived.

  12. 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.

  13. 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

  14. 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

  15. [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.

  16. Resistance to Clopidogrel among Iranian Patients Undergoing Angioplasty Intervention

    PubMed Central

    Haji Aghajani, Mohammad; Kobarfard, Farzad; Safi, Olia; Sheibani, Kourosh; Sistanizad, Mohammad

    2013-01-01

    To study the resistance to standard dosage of clopidogrel among Iranian patients following percutaneous coronary intervention measured by platelet aggregation test. Patients undergoing percutaneous coronary intervention in Imam Hussein Medical center, Tehran, Iran, who were under treatment with aspirin, but had no history of clopidogrel usage, entered the study. Patients received standard dosage of clopidogrel (Plavix®, Sanofi, France, 600 mg loading dose and 75 mg/day afterward). Platelet aggregation was measured using light transmission aggregometer. The response to the drug was categorized as complete resistance (platelet aggregation decreased less than 10%), intermediate resistance (platelet aggregation decreased between 10 to 30%) and complete response (platelet aggregation decreased to 30% or more). All patients were evaluated for major adverse cardio vascular events one month after the angioplasty based on MACE criteria by phone contact. Thirty-one patients with a mean age of 59 ± 13 entered the study. Sixty-five percent of patients showed complete response to clopidogrel (95% CI: 45% to 81%), 22% showed intermediate resistance (95% CI: 10-41%) and 13% showed complete resistance (95% CI: 4-30%). One month after the angioplasty, no major adverse cardiovascular event was recorded. Based on our findings, it seems that there is no major difference between Iranian population and other studies regarding the resistance to clopidogrel. Due to the limited number of participants in our study, further investigations with higher number of patients are recommended to more precisely calculate the percentage of resistance among Iranian patients. PMID:24250685

  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. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  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. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. Reducing psychological distress in patients undergoing chemotherapy.

    PubMed

    Milanti, Ariesta; Metsälä, Eija; Hannula, Leena

    Psychological distress is a common problem among patients with cancer, yet it mostly goes unreported and untreated. This study examined the association of a psycho-educational intervention with the psychological distress levels of breast cancer and cervical cancer patients undergoing chemotherapy. The design of the study was quasi-experimental, pretest-posttest design with a comparison group. One hundred patients at a cancer hospital in Jakarta, Indonesia, completed Distress Thermometer screening before and after chemotherapy. Fifty patients in the intervention group were given a psycho-educational video with positive reappraisal, education and relaxation contents, while receiving chemotherapy. Patients who received the psycho-educational intervention had significantly lower distress levels compared with those in the control group. Routine distress screening, followed by distress management and outcome assessment, is needed to improve the wellbeing of cancer patients.

  19. Nutrition assessment in patients undergoing liver transplant

    PubMed Central

    Bakshi, Neha; Singh, Kalyani

    2014-01-01

    Liver transplantation (LT) is a major surgery performed on patients with end stage liver disease. Nutrition is an integral part of patient care, and protein-energy malnutrition is almost universally present in patients suffering from liver disease undergoing LT. Nutrition assessment of preliver transplant phase helps to make a good nutrition care plan for the patients. Nutrition status has been associated with various factors which are related to the success of liver transplant such as morbidity, mortality, and length of hospital stay. To assess the nutritional status of preliver transplant patients, combinations of nutrition assessment methods should be used like subjective global assessment, Anthropometry mid arm-muscle circumference, Bioelectrical impedance analysis (BIA) and handgrip strength. PMID:25316978

  20. 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.

  1. [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.

  2. INTESTINAL MALROTATION IN PATIENTS UNDERGOING BARIATRIC SURGERY

    PubMed Central

    VIDAL, Eduardo Arevalo; RENDON, Francisco Abarca; ZAMBRANO, Trino Andrade; GARCÍA, Yudoco Andrade; VITERI, Mario Ferrin; CAMPOS, Josemberg Marins; RAMOS, Manoela Galvão; RAMOS, Almino Cardoso

    2016-01-01

    ABSTRACT Background: Intestinal malrotation is a rare congenital anomaly. In adults is very difficult to recognize due to the lack of symptoms. Diagnosis is usually incidental during surgical procedures or at autopsy. Aim: To review the occurrence and recognition of uneventful intestinal malrotation discovered during regular cases of bariatric surgeries. Methods: Were retrospectively reviewed the medical registry of 20,000 cases undergoing bariatric surgery, from January 2002 to January 2016, looking for the occurrence of intestinal malrotation and consequences in the intraoperative technique and immediate evolution of the patients. Results: Five cases (0,025%) of intestinal malrotation were found. All of them were males, aging 45, 49, 37,52 and 39 years; BMI 35, 42, 49, 47 and 52 kg/m2, all of them with a past medical history of morbid obesity. The patient with BMI 35 kg/m2 suffered from type 2 diabetes also. All procedures were completed by laparoscopic approach, with no conversions. In one patient was not possible to move the jejunum to the upper abdomen in order to establish the gastrojejunostomy and a sleeve gastrectomy was performed. In another patient was not possible to fully recognize the anatomy due to bowel adhesions and a single anastomosis gastric bypass was preferred. No leaks or bleeding were identified. There were no perioperative complications. All patients were discharged 72 h after the procedure and no immediate 30-day complications were reported. Conclusion: Patients with malrotation can successfully undergo laparoscopic bariatric surgery. May be necessary changes in the surgical original strategy regarding the malrotation. Surgeons must check full abdominal anatomical condition prior to start the division of the stomach. PMID:27683770

  3. 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.

  4. Evidence for mild thyroidal impairment in women undergoing endurance training

    SciTech Connect

    Boyden, T.W.; Pamenter, R.W.; Stanforth, P.; Rotkis, T.; Wilmore, J.H.

    1982-01-01

    The effects of endurance training on body composition and the pituitary-thyroid axis were studied in 29 healthy, young (mean age, 28.7 yr), regularly menstruating women. Women who were initially jogging a mean of 13.5 miles/week were selected for this study to minimize dropouts. Body composition, measured by hydrostatic weighing, and nonfasting plasma concentrations of T/sub 4/, T/sub 3/, rT/sub 3/, TSH, and TRH-stimulated TSH, measured by RIA, were examined initially and after each subject's weekly mileage had increased to 30 miles (..delta..30, mean total body weight did not change, mean fat weight decreased (-1.02 kg/ P<0.005), and mean lean weight increased (+0.75 kg; P<0.05). T/sub 4/ and unstimulated TSH did not change. However, mean (+/- SE) T/sub 3/ decreased from 107.2 +/- 4.4 to 97.9 +/- 3.4 ng/dl (P<0.025), and mean rT/sub 3/ decreased from 170.9 +/- 13.9 to 154.6 +/- 13.2 pg/ml (P<0.025). The decrease in T/sub 3/ and rT/sub 3/ were accompanied by significantly greater TSH responses to TRH stimulation (mean (+/- SE) area under TSH curve, 1381.4 +/- 123 vs. 1712.8 +/- 202 ..mu..IU/ml-min; P < 0.01). These results indicate that physically active women who undergo additional endurance training 1) become more lean without a change in total body weight, and 2) have changes in T/sub 3/, rT/sub 3/, and TRH-stimulated TSH indicative of mild thyroidal impairment.

  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. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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…

  12. 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.

  13. The piriform cortex and human focal epilepsy.

    PubMed

    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.

  14. 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

  15. 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

  16. 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…

  17. 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…

  18. 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…

  19. Solar-wind velocity decreases

    NASA Astrophysics Data System (ADS)

    Geranios, A.

    1980-08-01

    A model is developed to account for the solar wind electron and proton temperature decreases observed following the passage of an interplanetary shock wave and during the velocity decrease of a solar wind stream. The equations of mass and energy conservation are solved for a fully ionized, electrically neutral plasma expanding radially and spherically symmetrically, taking into account the heat flux from the solor corona to the plasma along the open magnetic field lines, and the electron thermal conductivity. An analytical relationship between the temperature and the velocity of the solar wind plasma is obtained which is found to be in agreement with experimental measurements made by the Vela 5 and 6 and IMP 6 satellites from August 1969-May 1974. It is thus proposed that the observed low plasma temperatures are due to the fact that the temperature decrease of the expanding plasma exceeds the heat gain due to thermal conduction from the corona.

  20. Transverse Mode Dynamics of VCSELs Undergoing Current Modulation

    NASA Technical Reports Server (NTRS)

    Goorjian, Peter M.; Ning, C. Z.; Agrawal, Govind

    2000-01-01

    Transverse mode dynamics of a 20-micron-diameter vertical-cavity surface-emitting laser (VCSEL) undergoing gain switching by deep current modulation is studied numerically. The direct current (dc) level is set slightly below threshold and is modulated by a large alternating current (ac). The resulting optical pulse train and transverse-mode patterns are obtained numerically. The ac frequency is varied from 2.5 GHz to 10 GHz, and the ac amplitude is varied from one-half to four times that of the dc level. At high modulation frequencies, a regular pulse train is not generated unless the ac amplitude is large enough. At all modulation frequencies, the transverse spatial profile switches from single-mode to multiple-mode pattern as the ac pumping level is increased. Optical pulse widths vary in the range 5-30 ps. with the pulse width decreasing when either the frequency is increased or the ac amplitude is decreased. The numerical modeling uses an approximation form of the semiconductor Maxwell-Bloch equations. Temporal evolution of the spatial profiles of the laser (and of carrier density) is determined without any assumptions about the type or number of modes. Keywords: VCSELs, current modulation, gain switching, transverse mode dynamics, computational modeling

  1. Preoperative Optimization of the Heart Failure Patient Undergoing Cardiac Surgery.

    PubMed

    Pichette, Maxime; Liszkowski, Mark; Ducharme, Anique

    2017-01-01

    Heart failure patients who undergo cardiac surgery are exposed to significant perioperative complications and high mortality. We herein review the literature concerning preoperative optimization of these patients. Salient findings are that end-organ dysfunction and medication should be optimized before surgery. Specifically: (1) reversible causes of anemia should be treated and a preoperative hemoglobin level of 100 g/L obtained; (2) renal function and volume status should be optimized; (3) liver function must be carefully evaluated; (4) nutritional status should be assessed and cachexia treated to achieve a preoperative albumin level of at least 30 g/L and a body mass index > 20; and (5) medication adjustments performed, such as withholding inhibitors of the renin-angiotensin-aldosterone system before surgery and continuing, but not starting, β-blockers. Levels of natriuretic peptides (brain natriuretic peptide [BNP] and N-terminal proBNP) provide additional prognostic value and therefore should be measured. In addition, individual patient's risk should be objectively assessed using standard formulas such as the EuroSCORE-II or Society of Thoracic Surgeons risk scores, which are simple and validated for various cardiac surgeries, including left ventricular assist device implantation. When patients are identified as high risk, preoperative hemodynamic optimization might be achieved with the insertion of a pulmonary artery catheter and hemodynamic-based tailored therapy. Finally, a prophylactic intra-aortic balloon pump might be considered in certain circumstances to decrease morbidity and even mortality, like in some high risk heart failure patients who undergo cardiac surgery, whereas routine preoperative inotropes are not recommended and should be reserved for patients in shock, except maybe for levosimendan.

  2. 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

  3. [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.

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. Olfactory experience modulates immature neuron development in postnatal and adult guinea pig piriform cortex.

    PubMed

    He, X; Zhang, X-M; Wu, J; Fu, J; Mou, L; Lu, D-H; Cai, Y; Luo, X-G; Pan, A; Yan, X-X

    2014-02-14

    Immature neurons expressing doublecortin (DCX+) are present around cortical layer II in various mammals including guinea pigs and humans, especially enriched in the paleocortex. However, little is known whether and how functional experience affects the development of this population of neurons. We attempted to explore a modulation by experience to layer II DCX+ cells in the primary olfactory cortex in postnatal and adult guinea pigs. Neonatal and 1-year-old guinea pigs were subjected to unilateral naris-occlusion, followed 1 and 2months later by morphometry of DCX+ cells in the piriform cortex. DCX+ somata and processes were reduced in the deprived relative to the non-deprived piriform cortex in both age groups at the two surviving time points. The number of DCX+ cells was decreased in the deprived side relative to internal control at 1 and 2months in the youths and at 2months in the adults post-occlusion. The mean somal area of DCX+ cells showed a trend of decrease in the deprived side relative to the internal control in the youths. In addition, DCX+ cells in the deprived side exhibited a lower frequency of colocalization with the neuron-specific nuclear antigen (NeuN) relative to counterparts. These results suggest that normal olfactory experience is required for the maintenance and development of DCX+ immature neurons in postnatal and adult guinea pig piriform cortex.

  10. 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].

  11. 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

  12. 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.

  13. Music and ambient operating room noise in patients undergoing spinal anesthesia.

    PubMed

    Ayoub, Chakib M; Rizk, Laudi B; Yaacoub, Chadi I; Gaal, Dorothy; Kain, Zeev N

    2005-05-01

    Previous studies have indicated that music decreases intraoperative sedative requirements in patients undergoing surgical procedures under regional anesthesia. In this study we sought to determine whether this decrease in sedative requirements results from music or from eliminating operating room (OR) noise. A secondary aim of the study was to examine the relationship of response to intraoperative music and participants' culture (i.e., American versus Lebanese). Eighty adults (36 American and 54 Lebanese) undergoing urological procedures with spinal anesthesia and patient-controlled IV propofol sedation were randomly assigned to intraoperative music, white noise, or OR noise. We found that, controlling for ambient OR noise, intraoperative music decreases propofol requirements (0.004 +/- 0.002 mg . kg(-1) . min(-1) versus 0.014 +/- 0.004 mg . kg(-1) . min(-1) versus 0.012 +/- 0.002 mg . kg(-1) . min(-1); P = 0.026). We also found that, regardless of group assignment, Lebanese patients used less propofol as compared with American patients (0.005 +/- 0.001 mg . kg(-1) . min(-1) versus 0.017 +/- 0.003 mg . kg(-1) . min(-1); P = 0.001) and that, in both sites, patients in the music group required less propofol (P < 0.05). We conclude that when controlling for ambient OR noise, intraoperative music decreases propofol requirements of both Lebanese and American patients who undergo urological surgery under spinal anesthesia.

  14. 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

  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. Constipation Risk in Patients Undergoing Abdominal Surgery

    PubMed Central

    Celik, Sevim; Atar, Nurdan Yalcin; Ozturk, Nilgun; Mendes, Guler; Kuytak, Figen; Bakar, Esra; Dalgiran, Duygu; Ergin, Sumeyra

    2015-01-01

    Background: Problems regarding bowel elimination are quite common in patients undergoing abdominal surgery. Objectives: To determine constipation risk before the surgery, bowel elimination during postoperative period, and the factors affecting bowel elimination. Patients and Methods: This is a cross-sectional study. It was conducted in a general surgery ward of a university hospital in Zonguldak, Turkey between January 2013 and May 2013. A total of 107 patients were included in the study, who were selected by convenience sampling. Constipation Risk Assessment Scale (CRAS), patient information form, medical and nursing records were used in the study. Results: The mean age of the patients was found to be 55.97 ± 15.74 (year). Most of the patients have undergone colon (37.4%) and stomach surgeries (21.5%). Open surgical intervention (83.2%) was performed on almost all patients (96.3%) under general anesthesia. Patients were at moderate risk for constipation with average scores of 11.71 before the surgery. A total of 77 patients (72%) did not have bowel elimination problem during postoperative period. The type of the surgery (P < 0.05), starting time for oral feeding after the surgery (P < 0.05), and mobilization (P < 0.05) were effective on postoperative bowel elimination. Conclusions: There is a risk for constipation after abdominal surgery. Postoperative practices are effective on the risk of constipation. PMID:26380107

  17. Masticatory muscles of mouse do not undergo atrophy in space

    PubMed Central

    Philippou, Anastassios; Minozzo, Fabio C.; Spinazzola, Janelle M.; Smith, Lucas R.; Lei, Hanqin; Rassier, Dilson E.; Barton, Elisabeth R.

    2015-01-01

    Muscle loading is important for maintaining muscle mass; when load is removed, atrophy is inevitable. However, in clinical situations such as critical care myopathy, masticatory muscles do not lose mass. Thus, their properties may be harnessed to preserve mass. We compared masticatory and appendicular muscles responses to microgravity, using mice aboard the space shuttle Space Transportation System-135. Age- and sex-matched controls remained on the ground. After 13 days of space flight, 1 masseter (MA) and tibialis anterior (TA) were frozen rapidly for biochemical and functional measurements, and the contralateral MA was processed for morphologic measurements. Flight TA muscles exhibited 20 ± 3% decreased muscle mass, 2-fold decreased phosphorylated (P)-Akt, and 4- to 12-fold increased atrogene expression. In contrast, MAs had no significant change in mass but a 3-fold increase in P-focal adhesion kinase, 1.5-fold increase in P-Akt, and 50–90% lower atrogene expression compared with limb muscles, which were unaltered in microgravity. Myofibril force measurements revealed that microgravity caused a 3-fold decrease in specific force and maximal shortening velocity in TA muscles. It is surprising that myofibril-specific force from both control and flight MAs were similar to flight TA muscles, yet power was compromised by 40% following flight. Continued loading in microgravity prevents atrophy, but masticatory muscles have a different set point that mimics disuse atrophy in the appendicular muscle.—Philippou, A., Minozzo, F. C., Spinazzola, J. M., Smith, L. R., Lei, H., Rassier, D. E., Barton, E. R. Masticatory muscles of mouse do not undergo atrophy in space. PMID:25795455

  18. Long-term modifications of synaptic efficacy in the human inferior and middle temporal cortex

    NASA Technical Reports Server (NTRS)

    Chen, W. R.; Lee, S.; Kato, K.; Spencer, D. D.; Shepherd, G. M.; Williamson, A.

    1996-01-01

    The primate temporal cortex has been demonstrated to play an important role in visual memory and pattern recognition. It is of particular interest to investigate whether activity-dependent modification of synaptic efficacy, a presumptive mechanism for learning and memory, is present in this cortical region. Here we address this issue by examining the induction of synaptic plasticity in surgically resected human inferior and middle temporal cortex. The results show that synaptic strength in the human temporal cortex could undergo bidirectional modifications, depending on the pattern of conditioning stimulation. High frequency stimulation (100 or 40 Hz) in layer IV induced long-term potentiation (LTP) of both intracellular excitatory postsynaptic potentials and evoked field potentials in layers II/III. The LTP induced by 100 Hz tetanus was blocked by 50-100 microM DL-2-amino-5-phosphonovaleric acid, suggesting that N-methyl-D-aspartate receptors were responsible for its induction. Long-term depression (LTD) was elicited by prolonged low frequency stimulation (1 Hz, 15 min). It was reduced, but not completely blocked, by DL-2-amino-5-phosphonovaleric acid, implying that some other mechanisms in addition to N-methyl-DL-aspartate receptors were involved in LTD induction. LTD was input-specific, i.e., low frequency stimulation of one pathway produced LTD of synaptic transmission in that pathway only. Finally, the LTP and LTD could reverse each other, suggesting that they can act cooperatively to modify the functional state of cortical network. These results suggest that LTP and LTD are possible mechanisms for the visual memory and pattern recognition functions performed in the human temporal cortex.

  19. Calbindins decreased after space flight

    NASA Technical Reports Server (NTRS)

    Sergeev, I. N.; Rhoten, W. B.; Carney, M. D.

    1996-01-01

    Exposure of the body to microgravity during space flight causes a series of well-documented changes in Ca2+ metabolism, yet the cellular and molecular mechanisms leading to these changes are poorly understood. Calbindins, vitamin D-dependent Ca2+ binding proteins, are believed to have a significant role in maintaining cellular Ca2+ homeostasis. In this study, we used biochemical and immunocytochemical approaches to analyze the expression of calbindin-D28k and calbindin-D9k in kidneys, small intestine, and pancreas of rats flown for 9 d aboard the space shuttle. The effects of microgravity on calbindins in rats from space were compared with synchronous Animal Enclosure Module controls, modeled weightlessness animals (tail suspension), and their controls. Exposure to microgravity resulted in a significant and sustained decrease in calbindin-D28k content in the kidney and calbindin-D9k in the small intestine of flight animals, as measured by enzyme-linked immunosorbent assay (ELISA). Modeled weightlessness animals exhibited a similar decrease in calbindins by ELISA. Immunocytochemistry (ICC) in combination with quantitative computer image analysis was used to measure in situ the expression of calbindins in the kidney and the small intestine, and the expression of insulin in pancreas. There was a large decrease of immunoreactivity in renal distal tubular cell-associated calbindin-D28k and in intestinal absorptive cell-associated calbindin-D9k of space flight and modeled weightlessness animals compared with matched controls. No consistent difference in pancreatic insulin immunoreactivity between space flight, modeled weightlessness, and controls was observed. Regression analysis of results obtained by quantitative ICC and ELISA for space flight, modeled weightlessness animals, and their controls demonstrated a significant correlation. These findings after a short-term exposure to microgravity or modeled weightlessness suggest that a decreased expression of calbindins

  20. Somatostatin and Neuropeptide Y Neurons Undergo Different Plasticity in Parahippocampal Regions in Kainic Acid–Induced Epilepsy

    PubMed Central

    Drexel, Meinrad; Kirchmair, Elke; Wieselthaler-Hölzl, Anna; Preidt, Adrian Patrick; Sperk, Günther

    2012-01-01

    Parahippocampal brain areas including the subiculum, presubiculum and parasubiculum, and entorhinal cortex give rise to major input and output neurons of the hippocampus and exert increased excitability in animal models and human temporal lobe epilepsy. Using immunohistochemistry and in situ hybridization for somatostatin and neuropeptide Y, we investigated plastic morphologic and neurochemical changes in parahippocampal neurons in the kainic acid (KA) model of temporal lobe epilepsy. Although constitutively contained in similar subclasses of γ-aminobutyric acid (GABA)-ergic neurons, both neuropeptide systems undergo distinctly different changes in their expression. Somatostatin messenger RNA (mRNA) is rapidly but transiently expressed de novo in pyramidal neurons of the subiculum and entorhinal cortex 24 hours after KA. Surviving somatostatin interneurons display increased mRNA levels at late intervals (3 months) after KA and increased labeling of their terminals in the outer molecular layer of the subiculum; the labeling correlates with the number of spontaneous seizures, suggesting that the seizures may trigger somatostatin expression. In contrast, neuropeptide Y mRNA is consistently expressed in principal neurons of the proximal subiculum and the lateral entorhinal cortex and labeling for the peptide persistently increased in virtually all major excitatory pathways of the hippocampal formation. The pronounced plastic changes differentially involving both neuropeptide systems indicate marked rearrangement of parahippocampal areas, presumably aiming at endogenous seizure protection. Their receptors may be targets for anticonvulsive drug therapy. PMID:22437342

  1. 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.

  2. 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

  3. Pyrrolidine dithiocarbamate protects the piriform cortex in the pilocarpine status epilepticus model.

    PubMed

    Soerensen, Jonna; Pekcec, Anton; Fuest, Christina; Nickel, Astrid; Potschka, Heidrun

    2009-12-01

    Pyrrolidine dithiocarbamate (PDTC) has a dual mechanism of action as an antioxidant and an inhibitor of the transcription factor kappa-beta. Both, production of reactive oxygen species as well as activation of NF-kappaB have been implicated in severe neuronal damage in different sub-regions of the hippocampus as well as in the surrounding cortices. The effect of PDTC on status epilepticus-associated cell loss in the hippocampus and piriform cortex was evaluated in the rat fractionated pilocarpine model. Treatment with 150 mg/kg PDTC before and following status epilepticus significantly increased the mortality rate to 100%. Administration of 50 mg/kg PDTC (low-dose) did not exert major effects on the development of a status epilepticus or the mortality rate. In vehicle-treated rats, status epilepticus caused pronounced neuronal damage in the piriform cortex comprising both pyramidal cells and interneurons. Low-dose PDTC treatment almost completely protected from lesions in the piriform cortex. A significant decrease in neuronal density of the hippocampal hilar formation was identified in vehicle- and PDTC-treated rats following status epilepticus. In conclusion, the NF-kappaB inhibitor and antioxidant PDTC protected the piriform cortex, whereas it did not affect hilar neuronal loss. These data might indicate that the generation of reactive oxygen species and activation of NF-kappaB plays a more central role in seizure-associated neuronal damage in the temporal cortex as compared to the hippocampal hilus. However, future investigations are necessary to exactly analyze the biochemical mechanisms by which PDTC exerted its beneficial effects in the piriform cortex.

  4. 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.

  5. Secular period decreasing of 17 detached chromospherically active binaries

    NASA Astrophysics Data System (ADS)

    Luo, C. Q.; Luo, Y. P.; Zhang, X. B.; Deng, L. C.; Luo, Z. Q.; Yang, S. Z.

    2008-10-01

    The long-term orbital period changes of detached chromospheric active binaries were surveyed. 17 of such systems are found to be undergoing secular period decreasing with the rates (dP/dt) of -3.05 × 10-9 to -3.77 × 10-5 days per year. The longer the orbital period, the more rapidly the period decreases. Following Stepien (1995), the period decreasing rate due to the angular momentum loss (AML) caused by magnetic wind is computed for each system. A comparison shows that the observed dP/dt's are obviously higher than that of the theoretical predictions by 1-3 orders of magnitude. It suggests that the magnetic wind is not likely the determinant mechanism driving the AML in close binaries.

  6. Chronic Stress Decreases Cerebrovascular Responses During Rat Hindlimb Electrical Stimulation

    PubMed Central

    Lee, Sohee; Kang, Bok-Man; Shin, Min-Kyoo; Min, Jiwoong; Heo, Chaejeong; Lee, Yubu; Baeg, Eunha; Suh, Minah

    2015-01-01

    Repeated stress is one of the major risk factors for cerebrovascular disease, including stroke, and vascular dementia. However, the functional alterations in the cerebral hemodynamic response induced by chronic stress have not been clarified. Here, we investigated the in vivo cerebral hemodynamic changes and accompanying cellular and molecular changes in chronically stressed rats. After 3 weeks of restraint stress, the elicitation of stress was verified by behavioral despair in the forced swimming test and by physical indicators of stress. The evoked changes in the cerebral blood volume and pial artery responses following hindpaw electrical stimulation were measured using optical intrinsic signal imaging. We observed that, compared to the control group, animals under chronic restraint stress exhibited a decreased hemodynamic response, with a smaller pial arterial dilation in the somatosensory cortex during hindpaw electrical stimulation. The effect of chronic restraint stress on vasomodulator enzymes, including neuronal nitric oxide synthase (nNOS) and heme oxygenase-2 (HO-2), was assessed in the somatosensory cortex. Chronic restraint stress downregulated nNOS and HO-2 compared to the control group. In addition, we examined the subtypes of cells that can explain the environmental changes due to the decreased vasomodulators. The expression of parvalbumin in GABAergic interneurons and glutamate receptor-1 in neurons were decreased, whereas the microglial activation was increased. Our results suggest that the chronic stress-induced alterations in cerebral vascular function and the modulations of the cellular expression in the neuro-vasomodulatory system may be crucial contributing factors in the development of various vascular-induced conditions in the brain. PMID:26778944

  7. Anterior Insular Cortex and Emotional Awareness

    PubMed Central

    Gu, Xiaosi; Hof, Patrick R.; Friston, Karl J.; Fan, Jin

    2014-01-01

    This paper reviews the foundation for a role of the human anterior insular cortex (AIC) in emotional awareness, defined as the conscious experience of emotions. We first introduce the neuroanatomical features of AIC and existing findings on emotional awareness. Using empathy, the awareness and understanding of other people’s emotional states, as a test case, we then present evidence to demonstrate: 1) AIC and anterior cingulate cortex (ACC) are commonly coactivated as revealed by a meta-analysis, 2) AIC is functionally dissociable from ACC, 3) AIC integrates stimulus-driven and top-down information, and 4) AIC is necessary for emotional awareness. We propose a model in which AIC serves two major functions: integrating bottom-up interoceptive signals with top-down predictions to generate a current awareness state and providing descending predictions to visceral systems that provide a point of reference for autonomic reflexes. We argue that AIC is critical and necessary for emotional awareness. PMID:23749500

  8. Monkey cortex through fMRI glasses.

    PubMed

    Vanduffel, Wim; Zhu, Qi; Orban, Guy A

    2014-08-06

    In 1998 several groups reported the feasibility of fMRI experiments in monkeys, with the goal to bridge the gap between invasive nonhuman primate studies and human functional imaging. These studies yielded critical insights in the neuronal underpinnings of the BOLD signal. Furthermore, the technology has been successful in guiding electrophysiological recordings and identifying focal perturbation targets. Finally, invaluable information was obtained concerning human brain evolution. We here provide a comprehensive overview of awake monkey fMRI studies mainly confined to the visual system. We review the latest insights about the topographic organization of monkey visual cortex and discuss the spatial relationships between retinotopy and category- and feature-selective clusters. We briefly discuss the functional layout of parietal and frontal cortex and continue with a summary of some fascinating functional and effective connectivity studies. Finally, we review recent comparative fMRI experiments and speculate about the future of nonhuman primate imaging.

  9. Barrel cortex and whisker-mediated behaviors.

    PubMed

    Brecht, Michael

    2007-08-01

    Neural networks of the rodent barrel cortex are particularly tractable for developing a quantitative understanding of response transformations in a cortical column. A column in barrel cortex consists of approximately 10 compartments. Two thalamic input pathways, a sensory lemniscal one and sensorimotor paralemniscal one, are transformed to approximately 7 population outputs, each with distinct spatiotemporal response characteristics. Granular and supragranular layers are sites of segregated processing in lemniscal and paralemniscal pathways, whereas infragranular layers are sites of intracolumnar, lemniscal/paralemniscal integration. Individual thalamocortical connections are relatively weak, and a considerable fraction of thalamocortical afferents contributes to each sensory response. Intracortically, relatively few but strong synaptic connections contribute to sensory responses, and responses are rapidly terminated by inhibition. Overall cortical population activity is very low. Whiskers mediate a wide range of behaviors and many natural tactile behaviors occur very rapidly. Vibrissal object recognition can be size invariant and motion invariant and is based on the tactile 'Gestaltwahrnehmung' of shape.

  10. Interareal synchronization in the visual cortex.

    PubMed

    Bressler, S L

    1996-04-01

    The primary visual cortex (V1) is part of a highly interconnected network of cortical areas, hierarchically organized but operating concurrently across hierarchical levels. The high degree of reciprocal interconnection among visual cortical areas provides a framework for their interaction during the performance of visual scene analysis. The functional interdependency of visual cortical areas which develops during scene analysis can be investigated by techniques which measure interareal correlated activity. Evidence from monkeys performing a visual pattern discrimination suggests that synchronization of aperiodic activity from neuronal ensembles in cortical areas at different hierarchical levels is a relevant aspect of visual function. The near-periodic nature of the synchronized response to moving light bars in earlier studies may have been a result of the type of stimulus used. Various models of visual cortex are discussed in which interareal synchronization plays a functional role.

  11. The role of prefrontal cortex in psychopathy

    PubMed Central

    Koenigs, Michael

    2014-01-01

    Psychopathy is a personality disorder characterized by remorseless and impulsive antisocial behavior. Given the significant societal costs of the recidivistic criminal activity associated with the disorder, there is a pressing need for more effective treatment strategies, and hence, a better understanding of the psychobiological mechanisms underlying the disorder. The prefrontal cortex (PFC) is likely to play an important role in psychopathy. In particular, the ventromedial and anterior cingulate sectors of PFC are theorized to mediate a number of social and affective decision-making functions that appear to be disrupted in psychopathy. This article provides a critical summary of human neuroimaging data implicating prefrontal dysfunction in psychopathy. A growing body of evidence associates psychopathy with structural and functional abnormalities in ventromedial PFC and anterior cingulate cortex. Although this burgeoning field still faces a number of methodological challenges and outstanding questions that will need to be resolved by future studies, the research to date has established a link between psychopathy and PFC. PMID:22752782

  12. The role of the premotor cortex and the primary motor cortex in action verb comprehension: evidence from Granger causality analysis.

    PubMed

    Yang, Jie; Shu, Hua

    2012-08-01

    Although numerous studies find the premotor cortex and the primary motor cortex are involved in action language comprehension, so far the nature of these motor effects is still in controversy. Some researchers suggest that the motor effects reflect that the premotor cortex and the primary motor cortex make functional contributions to the semantic access of action verbs, while other authors argue that the motor effects are caused by comprehension. In the current study, we used Granger causality analysis to investigate the roles of the premotor cortex and the primary motor cortex in processing of manual-action verbs. Regions of interest were selected in the primary motor cortex (M1) and the premotor cortex based on a hand motion task, and in the left posterior middle temporal gyrus (lexical semantic area) based on the reading task effect. We found that (1) the left posterior middle temporal gyrus had a causal influence on the left M1; and (2) the left posterior middle temporal gyrus and the left premotor cortex had bidirectional causal relations. These results suggest that the premotor cortex and the primary motor cortex play different roles in manual verb comprehension. The premotor cortex may be involved in motor simulation that contributes to action language processing, while the primary motor cortex may be engaged in a processing stage influenced by the meaning access of manual-action verbs. Further investigation combining effective connectivity analysis and technique with high temporal resolution is necessary for better clarification of the roles of the premotor cortex and the primary motor cortex in action language comprehension.

  13. 76 FR 27326 - Agency Forms Undergoing Paperwork Reduction Act Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-11

    ... Interpretation is a national systematic study investigating how the rapid evolution of laboratory medicine is... undergoing rapid change with the continuing introduction of new tests, increased focus on...

  14. The auditory representation of speech sounds in human motor cortex.

    PubMed

    Cheung, Connie; Hamiton, Liberty S; Johnson, Keith; Chang, Edward F

    2016-03-04

    In humans, listening to speech evokes neural responses in the motor cortex. This has been controversially interpreted as evidence that speech sounds are processed as articulatory gestures. However, it is unclear what information is actually encoded by such neural activity. We used high-density direct human cortical recordings while participants spoke and listened to speech sounds. Motor cortex neural patterns during listening were substantially different than during articulation of the same sounds. During listening, we observed neural activity in the superior and inferior regions of ventral motor cortex. During speaking, responses were distributed throughout somatotopic representations of speech articulators in motor cortex. The structure of responses in motor cortex during listening was organized along acoustic features similar to auditory cortex, rather than along articulatory features as during speaking. Motor cortex does not contain articulatory representations of perceived actions in speech, but rather, represents auditory vocal information.

  15. Early exposure to urethane anesthesia: Effects on neuronal activity in the piriform cortex of the developing brain.

    PubMed

    Kajiwara, Riichi; Takashima, Ichiro

    2015-07-23

    Exposure to urethane anesthesia reportedly produces selective neuronal cell loss in the piriform cortex of young brains; however, resulting functional deficits have not been investigated. The present study found abnormalities in piriform cortex activity of isolated brains in vitro that were harvested from guinea pigs exposed to urethane anesthesia at 14 days of age. Current source density (CSD) analysis and voltage-sensitive dye (VSD) imaging experiments were conducted 48h after urethane injection. We applied paired-pulse stimulation to the lateral olfactory tract (LOT) and assessed short-interval intra-cortical inhibition in the piriform cortex. CSD analysis revealed that a current sink in layer Ib remained active in response to successive stimuli, with an inter-stimulus interval of 30-60 ms, which was typically strongly inhibited. VSD imaging demonstrated stronger and extended neural activity in the urethane-treated piriform cortex, even in response to a second stimulus delivered in short succession. We identified gamma-aminobutyric acid (GABA) ergic neurons in the piriform cortex of sham and urethane-treated animals and found a decrease in GABA-immunoreactive cell density in the urethane group. These results suggest that urethane exposure induces loss of GABAergic interneurons and a subsequent reduction in paired-pulse inhibition in the immature piriform cortex.

  16. Decreasing Fires in Mediterranean Europe.

    PubMed

    Turco, Marco; Bedia, Joaquín; Di Liberto, Fabrizio; Fiorucci, Paolo; von Hardenberg, Jost; Koutsias, Nikos; Llasat, Maria-Carmen; Xystrakis, Fotios; Provenzale, Antonello

    2016-01-01

    Forest fires are a serious environmental hazard in southern Europe. Quantitative assessment of recent trends in fire statistics is important for assessing the possible shifts induced by climate and other environmental/socioeconomic changes in this area. Here we analyse recent fire trends in Portugal, Spain, southern France, Italy and Greece, building on a homogenized fire database integrating official fire statistics provided by several national/EU agencies. During the period 1985-2011, the total annual burned area (BA) displayed a general decreasing trend, with the exception of Portugal, where a heterogeneous signal was found. Considering all countries globally, we found that BA decreased by about 3020 km2 over the 27-year-long study period (i.e. about -66% of the mean historical value). These results are consistent with those obtained on longer time scales when data were available, also yielding predominantly negative trends in Spain and France (1974-2011) and a mixed trend in Portugal (1980-2011). Similar overall results were found for the annual number of fires (NF), which globally decreased by about 12600 in the study period (about -59%), except for Spain where, excluding the provinces along the Mediterranean coast, an upward trend was found for the longer period. We argue that the negative trends can be explained, at least in part, by an increased effort in fire management and prevention after the big fires of the 1980's, while positive trends may be related to recent socioeconomic transformations leading to more hazardous landscape configurations, as well as to the observed warming of recent decades. We stress the importance of fire data homogenization prior to analysis, in order to alleviate spurious effects associated with non-stationarities in the data due to temporal variations in fire detection efforts.

  17. Decreasing Fires in Mediterranean Europe

    PubMed Central

    Turco, Marco; Bedia, Joaquín; Di Liberto, Fabrizio; Fiorucci, Paolo; von Hardenberg, Jost; Koutsias, Nikos; Llasat, Maria-Carmen; Xystrakis, Fotios; Provenzale, Antonello

    2016-01-01

    Forest fires are a serious environmental hazard in southern Europe. Quantitative assessment of recent trends in fire statistics is important for assessing the possible shifts induced by climate and other environmental/socioeconomic changes in this area. Here we analyse recent fire trends in Portugal, Spain, southern France, Italy and Greece, building on a homogenized fire database integrating official fire statistics provided by several national/EU agencies. During the period 1985-2011, the total annual burned area (BA) displayed a general decreasing trend, with the exception of Portugal, where a heterogeneous signal was found. Considering all countries globally, we found that BA decreased by about 3020 km2 over the 27-year-long study period (i.e. about -66% of the mean historical value). These results are consistent with those obtained on longer time scales when data were available, also yielding predominantly negative trends in Spain and France (1974-2011) and a mixed trend in Portugal (1980-2011). Similar overall results were found for the annual number of fires (NF), which globally decreased by about 12600 in the study period (about -59%), except for Spain where, excluding the provinces along the Mediterranean coast, an upward trend was found for the longer period. We argue that the negative trends can be explained, at least in part, by an increased effort in fire management and prevention after the big fires of the 1980’s, while positive trends may be related to recent socioeconomic transformations leading to more hazardous landscape configurations, as well as to the observed warming of recent decades. We stress the importance of fire data homogenization prior to analysis, in order to alleviate spurious effects associated with non-stationarities in the data due to temporal variations in fire detection efforts. PMID:26982584

  18. Use of Dexmedetomidine in Patients Undergoing Craniotomies

    PubMed Central

    Jadhav, Nalini; Wagaskar, Vinayak; Kondwilkar, Bharati; Patil, Rajesh

    2017-01-01

    Introduction The neuroanaesthesia ensures stable perioperative cerebral haemodynamics, avoids sudden rise in intracranial pressure and prevents acute brain swelling. The clinical characteristics of dexmeditomidine make this intravenous agent a potentially attractive adjunct for neuroanaesthesia and in the neurological intensive care unit. Aim This study aimed to assess the effect of dexmedetomidine on intraoperative haemodynamic stability and to assess the intraoperative requirements of analgesic and other anaesthetic agents, and also to assess postoperative sedation, respiratory depression and any other side effects of dexmedetomidine as compared to placebo. Materials and Methods This prospective randomized study was done in 60 patients of either sex, age between 18 to 60 years and American Society of Anaesthesiologist (ASA) Grade I and II undergoing elective craniotomies under General Anaesthesia (GA) for intracranial Space Occupying Lesion (SOL). These 60 patients underwent thorough history, clinical examination and laboratory investigations. They were randomly divided into two groups, Group D (received Inj. Dexmedetomidine) and Group P (received Inj. Placebo). During bolus and infusion Heart Rate (HR), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Pressure (MAP), Peripheral oxygen saturation (SPO2) was recorded at every five minutes interval for first 20 minute. Results The mean age in Group D was 39.5 years and in Group P was 40 years. The sex distribution in two groups was in Group D, 12 patients (40%) were females and 18 (60%) patients were males. While in Group P 10 (33.3%) were females and 20 (66.7%) patients were males. The two groups were comparable with respect to diagnosis and type of surgery of patients and difference was not statistically significant. The mean HR, the mean DBP and the mean MAP was lower in Group D as compared to Group P and the difference was statistically significant. Conclusion Dexmedetomidine

  19. Thermoelectric device exhibiting decreased stress

    SciTech Connect

    Heath, D.L.; Chou, D.J.

    1985-02-05

    A thermoelectric device exhibiting both structural integrity and decreased stress across the device notwithstanding the application of thermally cycled temperature differentials thereacross includes, electrically interconnected thermoelectric elements and a rigidly affixed substrate. Thermal stress is relieved by using flexible conductors to interconnect the thermoelectric elements, and by the use of a flexile joint to attach a second substrate to the remainder of the device. Complete elimination of the second substrate may also be used to eliminate stress. Presence of the rigidly affixed substrate gives the device sufficient structural integrity to enable it to withstand rugged conditions.

  20. Technologies for Decreasing Mining Losses

    NASA Astrophysics Data System (ADS)

    Valgma, Ingo; Väizene, Vivika; Kolats, Margit; Saarnak, Martin

    2013-12-01

    In case of stratified deposits like oil shale deposit in Estonia, mining losses depend on mining technologies. Current research focuses on extraction and separation possibilities of mineral resources. Selective mining, selective crushing and separation tests have been performed, showing possibilities of decreasing mining losses. Rock crushing and screening process simulations were used for optimizing rock fractions. In addition mine backfilling, fine separation, and optimized drilling and blasting have been analyzed. All tested methods show potential and depend on mineral usage. Usage in addition depends on the utilization technology. The questions like stability of the material flow and influences of the quality fluctuations to the final yield are raised.

  1. Kinetics of plasma membrane and mitochondrial alterations in cells undergoing apoptosis

    SciTech Connect

    Lizard, G.; Fournel, S.; Genestier, L.; Dhedin, N.

    1995-11-01

    Programmed cell death or apoptosis is characterized by typical morphological alterations. By transmission electron microscopy, apoptotic cells are identified by condensation of the chromatin in tight apposition to the nuclear envelope, alteration of the nuclear envelope and fragmentation of the nucleus, whereas integrity of the plasma membrane and organelles is preserved. Conversely cells undergoing necrosis display and early desintegration of cytoplasmic membrane and swelling of mitochondria. In this study we assessed by flow cytometry the sequential alterations of forward angle light scatter, 90{degrees} light scatter, and fluorescence associated with fluorescein diacetate, rhodamine 123, and propidium iodide in two human B cell lines undergoing apoptosis induced by the topoisomerase II inhibitor VP-16. The kinetics of these modifications were compared to those of cells undergoing necrosis induced by the topoisomerase II inhibitor VP-16. The kinetics of these modifications were compared to those of cells undergoing necrosis induced by sodium azide. At the same time intervals, cells were examined by transmission electron microscopy and by UV microscopy after staining with Hoechst 33342. We report that sequential changes in light scatters and fluorescein diacetate are similar in cells undergoing apoptosis or necrosis, whereas apoptosis is characterized by a slightly delayed decrease of mitochondrial activity as assessed by rhodamine 123 staining. Surprisingly, a part of cells undergoing apoptosis displayed an early uptake of propidium iodide followed by a condensation and then a fragmentation of their nuclei. It is concluded that uptake of propidium iodide is a very early marker of cell death which does not discriminate between necrosis and apoptosis. Along with biochemical criteria, nuclear morphology revealed by staining with Hoechst 33342 would seem to be of the most simple and most discriminative assay of apoptosis. 33 refs., 5 figs., 1 tab.

  2. Human prefrontal cortex: evolution, development, and pathology.

    PubMed

    Teffer, Kate; Semendeferi, Katerina

    2012-01-01

    The prefrontal cortex is critical to many cognitive abilities that are considered particularly human, and forms a large part of a neural system crucial for normal socio-emotional and executive functioning in humans and other primates. In this chapter, we survey the literature regarding prefrontal development and pathology in humans as well as comparative studies of the region in humans and closely related primate species. The prefrontal cortex matures later in development than more caudal regions, and some of its neuronal subpopulations exhibit more complex dendritic arborizations. Comparative work suggests that the human prefrontal cortex differs from that of closely related primate species less in relative size than it does in organization. Specific reorganizational events in neural circuitry may have taken place either as a consequence of adjusting to increases in size or as adaptive responses to specific selection pressures. Living in complex environments has been recognized as a considerable factor in the evolution of primate cognition. Normal frontal lobe development and function are also compromised in several neurological and psychiatric disorders. A phylogenetically recent reorganization of frontal cortical circuitry may have been critical to the emergence of human-specific executive and social-emotional functions, and developmental pathology in these same systems underlies many psychiatric and neurological disorders, including autism and schizophrenia.

  3. Rhythmic spontaneous activity in the piriform cortex.

    PubMed

    Sanchez-Vives, Maria V; Descalzo, V F; Reig, R; Figueroa, N A; Compte, A; Gallego, R

    2008-05-01

    Slow spontaneous rhythmic activity is generated and propagates in neocortical slices when bathed in an artificial cerebrospinal fluid with ionic concentrations similar to the ones in vivo. This activity is extraordinarily similar to the activation of the cortex in physiological conditions (e.g., slow-wave sleep), thus representing a unique in vitro model to understand how cortical networks maintain and control ongoing activity. Here we have characterized the activity generated in the olfactory or piriform cortex and endopiriform nucleus (piriform network). Because these structures are prone to generate epileptic discharges, it seems critical to understand how they generate and regulate their physiological rhythmic activity. The piriform network gave rise to rhythmic spontaneous activity consisting of a succession of up and down states at an average frequency of 1.8 Hz, qualitatively similar to the corresponding neocortical activity. This activity originated in the deep layers of the piriform network, which displayed higher excitability and denser connectivity. A remarkable difference with neocortical activity was the speed of horizontal propagation (114 mm/s), one order of magnitude faster in the piriform network. Properties of the piriform cortex subserving fast horizontal propagation may underlie the higher vulnerability of this area to epileptic seizures.

  4. Does intrinsic motivation enhance motor cortex excitability?

    PubMed

    Radel, Rémi; Pjevac, Dusan; Davranche, Karen; d'Arripe-Longueville, Fabienne; Colson, Serge S; Lapole, Thomas; Gruet, Mathieu

    2016-11-01

    Intrinsic motivation (IM) is often viewed as a spontaneous tendency for action. Recent behavioral and neuroimaging evidence indicate that IM, in comparison to extrinsic motivation (EM), solicits the motor system. Accordingly, we tested whether IM leads to greater excitability of the motor cortex than EM. To test this hypothesis, we used two different tasks to induce the motivational orientation using either words representing each motivational orientation or pictures previously linked to each motivational orientation through associative learning. Single-pulse transcranial magnetic stimulation over the motor cortex was applied when viewing the stimuli. Electromyographic activity was recorded on the contracted first dorsal interosseous muscle. Two indexes of corticospinal excitability (the amplitude of motor-evoked potential and the length of cortical silent period) were obtained through unbiased automatic detection and analyzed using a mixed model that provided both statistical power and a high level of control over all important individual, task, and stimuli characteristics. Across the two tasks and the two indices of corticospinal excitability, the exposure to IM-related stimuli did not lead to a greater corticospinal excitability than EM-related stimuli or than stimuli with no motivational valence (ps > .20). While these results tend to dismiss the advantage of IM at activating the motor cortex, we suggest alternative hypotheses to explain this lack of effect, which deserves further research.

  5. Salient sounds activate human visual cortex automatically

    PubMed Central

    McDonald, John J.; Störmer, Viola S.; Martinez, Antigona; Feng, Wenfeng; Hillyard, Steven A.

    2013-01-01

    Sudden changes in the acoustic environment enhance perceptual processing of subsequent visual stimuli that appear in close spatial proximity. Little is known, however, about the neural mechanisms by which salient sounds affect visual processing. In particular, it is unclear whether such sounds automatically activate visual cortex. To shed light on this issue, the present study examined event-related brain potentials (ERPs) that were triggered either by peripheral sounds that preceded task-relevant visual targets (Experiment 1) or were presented during purely auditory tasks (Experiments 2, 3, and 4). In all experiments the sounds elicited a contralateral ERP over the occipital scalp that was localized to neural generators in extrastriate visual cortex of the ventral occipital lobe. The amplitude of this cross-modal ERP was predictive of perceptual judgments about the contrast of co-localized visual targets. These findings demonstrate that sudden, intrusive sounds reflexively activate human visual cortex in a spatially specific manner, even during purely auditory tasks when the sounds are not relevant to the ongoing task. PMID:23699530

  6. Hierarchical Bayesian inference in the visual cortex

    NASA Astrophysics Data System (ADS)

    Lee, Tai Sing; Mumford, David

    2003-07-01

    Traditional views of visual processing suggest that early visual neurons in areas V1 and V2 are static spatiotemporal filters that extract local features from a visual scene. The extracted information is then channeled through a feedforward chain of modules in successively higher visual areas for further analysis. Recent electrophysiological recordings from early visual neurons in awake behaving monkeys reveal that there are many levels of complexity in the information processing of the early visual cortex, as seen in the long-latency responses of its neurons. These new findings suggest that activity in the early visual cortex is tightly coupled and highly interactive with the rest of the visual system. They lead us to propose a new theoretical setting based on the mathematical framework of hierarchical Bayesian inference for reasoning about the visual system. In this framework, the recurrent feedforward/feedback loops in the cortex serve to integrate top-down contextual priors and bottom-up observations so as to implement concurrent probabilistic inference along the visual hierarchy. We suggest that the algorithms of particle filtering and Bayesian-belief propagation might model these interactive cortical computations. We review some recent neurophysiological evidences that support the plausibility of these ideas. 2003 Optical Society of America

  7. Hemispherical map for the human brain cortex

    NASA Astrophysics Data System (ADS)

    Tosun, Duygu; Prince, Jerry L.

    2001-07-01

    Understanding the function of the human brain cortex is a primary goal in human brain mapping. Methods to unfold and flatten the cortical surface for visualization and measurement have been described in previous literature; but comparison across multiple subjects is still difficult because of the lack of a standard mapping technique. We describe a new approach that maps each hemisphere of the cortex to a portion of a sphere in a standard way, making comparison of anatomy and function across different subjects possible. Starting with a three-dimensional magnetic resonance image of the brain, the cortex is segmented and represented as a triangle mesh. Defining a cut around the corpus collosum identifies the left and right hemispheres. Together, the two hemispheres are mapped to the complex plane using a conformal mapping technique. A Mobius transformation, which is conformal, is used to transform the points on the complex plane so that a projective transformation maps each brain hemisphere onto a spherical segment comprising a sphere with a cap removed. We determined the best size of the spherical cap by minimizing the relative area distortion between hemispherical maps and original cortical surfaces. The relative area distortion between the hemispherical maps and the original cortical surfaces for fifteen human brains is analyzed.

  8. Functional subregions of the human entorhinal cortex

    PubMed Central

    Maass, Anne; Berron, David; Libby, Laura A; Ranganath, Charan; Düzel, Emrah

    2015-01-01

    The entorhinal cortex (EC) is the primary site of interactions between the neocortex and hippocampus. Studies in rodents and nonhuman primates suggest that EC can be divided into subregions that connect differentially with perirhinal cortex (PRC) vs parahippocampal cortex (PHC) and with hippocampal subfields along the proximo-distal axis. Here, we used high-resolution functional magnetic resonance imaging at 7 Tesla to identify functional subdivisions of the human EC. In two independent datasets, PRC showed preferential intrinsic functional connectivity with anterior-lateral EC and PHC with posterior-medial EC. These EC subregions, in turn, exhibited differential connectivity with proximal and distal subiculum. In contrast, connectivity of PRC and PHC with subiculum followed not only a proximal-distal but also an anterior-posterior gradient. Our data provide the first evidence that the human EC can be divided into functional subdivisions whose functional connectivity closely parallels the known anatomical connectivity patterns of the rodent and nonhuman primate EC. DOI: http://dx.doi.org/10.7554/eLife.06426.001 PMID:26052749

  9. Linear summation of cat motor cortex outputs.

    PubMed

    Ethier, Christian; Brizzi, Laurent; Darling, Warren G; Capaday, Charles

    2006-05-17

    Recruitment of movement-related muscle synergies involves the functional linking of motor cortical points. We asked how the outputs of two simultaneously stimulated motor cortical points would interact. To this end, experiments were done in ketamine-anesthetized cats. When prolonged (e.g., 500 ms) trains of intracortical microstimulation were applied in the primary motor cortex, stimulus currents as low as 10-20 microA evoked coordinated movements of the contralateral forelimb. Paw kinematics in three dimensions and the electromyographic (EMG) activity of eight muscles were simultaneously recorded. We show that the EMG outputs of two cortical points simultaneously stimulated are additive. The movements were represented as displacement vectors pointing from initial to final paw position. The displacement vectors resulting from simultaneous stimulation of two cortical points pointed in nearly the same direction as the algebraic resultant vector. Linear summation of outputs was also found when inhibition at one of the cortical points was reduced by GABAA receptor antagonists. A simple principle emerges from these results. Notwithstanding the underlying complex neuronal circuitry, motor cortex outputs combine nearly linearly in terms of movement direction and muscle activation patterns. Importantly, simultaneous activation does not change the nature of the output at each point. An additional implication is that not all possible movements need be explicitly represented in the motor cortex; a large number of different movements may be synthesized from a smaller repertoire.

  10. MDMA administration decreases serotonin but not N-acetylaspartate in the rat brain

    PubMed Central

    Perrine, Shane A.; Ghoddoussi, Farhad; Michaels, Mark S.; Hyde, Elisabeth M.; Kuhn, Donald M.; Galloway, Matthew P.

    2010-01-01

    In animals, repeated administration of 3,4-methylenedioxymethamphetamine (MDMA) reduces markers of serotonergic activity and studies show similar serotonergic deficits in human MDMA users. Using proton magnetic resonance spectroscopy (1H-MRS) at 11.7 Tesla, we measured the metabolic neurochemical profile in intact, discrete tissue punches taken from prefrontal cortex, anterior striatum, and hippocampus of rats administered MDMA (5 mg/kg IP, 4× q 2 h) or saline and euthanized 7 days after the last injection. Monoamine content was measured with HPLC in contralateral punches from striatum and hippocampus to compare the MDMA-induced loss of 5HT innervation with constituents in the 1H-MRS profile. When assessed 7 days after the last MDMA injection, levels of hippocampal and striatal serotonin (5HT) were significantly reduced, consistent with published animal studies. N-acetylaspartate (NAA) levels were significantly increased in prefrontal cortex and not affected in anterior striatum or hippocampus; myo-inositol (INS) levels were increased in prefrontal cortex and hippocampus but not anterior striatum. Glutamate levels were increased in prefrontal cortex and decreased in hippocampus, while GABA levels were decreased only in hippocampus. The data suggest that NAA may not reliably reflect MDMA-induced 5HT neurotoxicity. However, the collective pattern of changes in 5HT, INS, glutamate and GABA is consistent with persistent hippocampal neuroadaptations caused by MDMA. PMID:20800616

  11. Silibinin attenuates cognitive deficits and decreases of dopamine and serotonin induced by repeated methamphetamine treatment.

    PubMed

    Lu, Ping; Mamiya, Takayoshi; Lu, Lingling; Mouri, Akihiro; Niwa, Minae; Kim, Hyoung-Chun; Zou, Li-Bo; Nagai, Taku; Yamada, Kiyofumi; Ikejima, Takashi; Nabeshima, Toshitaka

    2010-03-05

    Cognitive deficits are a core feature of patients with methamphetamine (METH) abuse. It has been reported that repeated METH treatment impairs long-term recognition memory in the novel object recognition test (NORT) in mice. Recent studies indicate that silibinin, a flavonoid derived from the herb milk thistle, has potent neuroprotective effects in cell cultures and several animal models of neurological diseases. However, its effect on the cognitive deficit induced by METH remains unclear. In the present study, we attempt to clarify the effect of silibinin on impairments of recognition memory caused by METH in mice. Mice were co-administered silibinin with METH for 7 days and then cognitive function was assessed by NORT after 7-day withdrawal. Tissue levels of dopamine and serotonin as well as their metabolites in the prefrontal cortex and hippocampus were measured 1 day after NORT. Silibinin dose-dependently ameliorated the impairment of recognition memory caused by METH treatment in mice. Silibinin significantly attenuated the decreases in the dopamine content of the prefrontal cortex and serotonin content of the hippocampus caused by METH treatment. We also found a correlation between the recognition values and dopamine and serotonin contents of the prefrontal cortex and hippocampus. The effect of silibinin on cognitive impairment may be associated with an amelioration of decreases in dopamine and serotonin levels in the prefrontal cortex and hippocampus, respectively. These results suggest that silibinin may be useful as a pharmacological tool to investigate the mechanisms of METH-induced cognitive impairments.

  12. Medial entorhinal cortex lesions only partially disrupt hippocampal place cells and hippocampus-dependent place memory

    PubMed Central

    Hales, Jena B; Schlesiger, Magdalene I; Leutgeb, Jill K; Squire, Larry R; Leutgeb, Stefan; Clark, Robert E

    2014-01-01

    SUMMARY Entorhinal cortex provides the primary cortical projections to the hippocampus, a brain structure critical for memory. However, it remains unclear how the precise firing patterns of medial entorhinal cortex (MEC) cells influence hippocampal physiology and hippocampus-dependent behavior. We found that complete bilateral lesions of MEC resulted in a lower proportion of active hippocampal cells. The remaining active cells had place fields, but with decreased spatial precision and decreased long-term spatial stability. In addition, MEC rats were as impaired at acquiring the watermaze as hippocampus rats, while rats with combined MEC and hippocampal lesions had an even greater deficit. However, MEC rats were not impaired on other hippocampus-dependent tasks, including those in which an object location or context was remembered. Thus, MEC is not necessary for all types of spatial coding, nor for all types of hippocampus-dependent memory, but is necessary for the normal acquisition of place memory. PMID:25437546

  13. The effects of motor cortex rTMS on corticospinal descending activity.

    PubMed

    Di Lazzaro, V; Profice, P; Pilato, F; Dileone, M; Oliviero, A; Ziemann, U

    2010-04-01

    Repetitive transcranial magnetic stimulation (rTMS) of the human motor cortex can produce long-lasting changes in the excitability of the motor cortex to single pulse transcranial magnetic stimulation (TMS). rTMS may increase or decrease motor cortical excitability depending critically on the characteristics of the stimulation protocol. However, it is still poorly defined which mechanisms and central motor circuits contribute to these rTMS induced long-lasting excitability changes. We have had the opportunity to perform a series of direct recordings of the corticospinal volley evoked by single pulse TMS from the epidural space of conscious patients with chronically implanted spinal electrodes before and after several protocols of rTMS that increase or decrease brain excitability. These recordings provided insight into the physiological basis of the effects of rTMS and the specific motor cortical circuits involved.

  14. Higher susceptibility of cerebral cortex and striatum to sulfite neurotoxicity in sulfite oxidase-deficient rats.

    PubMed

    Grings, Mateus; Moura, Alana Pimentel; Parmeggiani, Belisa; Motta, Marcela Moreira; Boldrini, Rafael Mello; August, Pauline Maciel; Matté, Cristiane; Wyse, Angela T S; Wajner, Moacir; Leipnitz, Guilhian

    2016-11-01

    Patients affected by sulfite oxidase (SO) deficiency present severe seizures early in infancy and progressive neurological damage, as well as tissue accumulation of sulfite, thiosulfate and S-sulfocysteine. Since the pathomechanisms involved in the neuropathology of SO deficiency are still poorly established, we evaluated the effects of sulfite on redox homeostasis and bioenergetics in cerebral cortex, striatum, cerebellum and hippocampus of rats with chemically induced SO deficiency. The deficiency was induced in 21-day-old rats by adding 200ppm of tungsten, a molybdenum competitor, in their drinking water for 9weeks. Sulfite (70mg/kg/day) was also administered through the drinking water from the third week of tungsten supplementation until the end of the treatment. Sulfite decreased reduced glutathione concentrations and the activities of glutathione reductase and glutathione S-transferase (GST) in cerebral cortex and of GST in cerebellum of SO-deficient rats. Moreover, sulfite increased the activities of complexes II and II-III in striatum and of complex II in hippocampus, but reduced the activity of complex IV in striatum of SO-deficient rats. Sulfite also decreased the mitochondrial membrane potential in cerebral cortex and striatum, whereas it had no effect on mitochondrial mass in any encephalic tissue evaluated. Finally, sulfite inhibited the activities of malate and glutamate dehydrogenase in cerebral cortex of SO-deficient rats. Taken together, our findings indicate that cerebral cortex and striatum are more vulnerable to sulfite-induced toxicity than cerebellum and hippocampus. It is presumed that these pathomechanisms may contribute to the pathophysiology of neurological damage found in patients affected by SO deficiency.

  15. Nature experience reduces rumination and subgenual prefrontal cortex activation

    PubMed Central

    Bratman, Gregory N.; Hamilton, J. Paul; Hahn, Kevin S.; Daily, Gretchen C.; Gross, James J.

    2015-01-01

    Urbanization has many benefits, but it also is associated with increased levels of mental illness, including depression. It has been suggested that decreased nature experience may help to explain the link between urbanization and mental illness. This suggestion is supported by a growing body of correlational and experimental evidence, which raises a further question: what mechanism(s) link decreased nature experience to the development of mental illness? One such mechanism might be the impact of nature exposure on rumination, a maladaptive pattern of self-referential thought that is associated with heightened risk for depression and other mental illnesses. We show in healthy participants that a brief nature experience, a 90-min walk in a natural setting, decreases both self-reported rumination and neural activity in the subgenual prefrontal cortex (sgPFC), whereas a 90-min walk in an urban setting has no such effects on self-reported rumination or neural activity. In other studies, the sgPFC has been associated with a self-focused behavioral withdrawal linked to rumination in both depressed and healthy individuals. This study reveals a pathway by which nature experience may improve mental well-being and suggests that accessible natural areas within urban contexts may be a critical resource for mental health in our rapidly urbanizing world. PMID:26124129

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

    PubMed

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

    2008-10-21

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

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

    PubMed

    Deen, Ben; Saxe, Rebecca; Bedny, Marina

    2015-08-01

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

  18. Decreased Thalamocortical Connectivity in Chronic Ketamine Users

    PubMed Central

    Liao, Yanhui; Tang, Jinsong; Liu, Jianbin; Xie, An; Yang, Mei; Johnson, Maritza; Wang, Xuyi; Deng, Qijian; Chen, Hongxian; Xiang, Xiaojun; Liu, Tieqiao; Chen, Xiaogang; Song, Ming; Hao, Wei

    2016-01-01

    Disintegration in thalamocortical integration suggests its role in the mechanistic ‘switch’ from recreational to dysregulated drug seeking/addiction. In this study, we aimed to address whether thalamic nuclear groups show altered functional connectivity within the cerebral cortex in chronic ketamine users. One hundred and thirty subjects (41 ketamine users and 89 control subjects) underwent rsfMRI (resting-state functional Magnetic Resonance Imaging). Based on partial correlation functional connectivity analysis we partitioned the thalamus into six nuclear groups that correspond well with human histology. Then, in the area of each nuclear group, the functional connectivity differences between the chronic ketamine user group and normal control group were investigated. We found that the ketamine user group showed significantly less connectivity between the thalamic nuclear groups and the cortical regions-of-interest, including the prefrontal cortex, the motor cortex /supplementary motor area, and the posterior parietal cortex. However, no increased thalamic connectivity was observed for these regions as compared with controls. This study provides the first evidence of abnormal thalamocortical connectivity of resting state brain activity in chronic ketamine users. Further understanding of pathophysiological mechanisms of the thalamus in addiction (ketamine addiction) may facilitate the evaluation of much-needed novel pharmacological agents for improved therapy of this complex disease. PMID:27977717

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

    PubMed

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

    2015-02-01

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

  20. Retention of free liquids in landfills undergoing vertical expansion

    SciTech Connect

    Zornberg, J.G.; Jernigan, B.L.; Sanglerat, T.R.; Cooley, B.H.

    1999-07-01

    This paper presents the results of an evaluation of the potential release of liquids stored within a waste mass undergoing compression due to a landfill vertical expansion. The mechanism of free liquid generation is initially evaluated and data interpretation methods are developed to estimate the maximum allowable waste thickness that a landfill could reach without releasing liquids stored within the waste. The proposed conceptual framework of free liquid generation is used to evaluate the environmental implications of the vertical expansion of an unlined case history landfill located in southern California. The moisture content of waste in southern California landfills is generally below field capacity. However, if the waste is compressed, its available moisture-holding capacity will decrease and its moisture content may eventually reach field capacity. Additional compression beyond this point will squeeze liquid from the waste. Laboratory testing and field characterization programs were undertaken to evaluate the field capacity, the in-situ moisture distribution, and the unit weight profiles of the waste in the case history landfill. These experimental data were used to evaluate the ability of the landfill to continue to retain moisture after continued waste placement. The evaluation indicated that the moisture content of the waste will not reach its field capacity for the proposed final grading of the case history landfill and, therefore, that the liquids should remain within the waste mass after the vertical expansion.

  1. Value of extended warming in patients undergoing elective surgery.

    PubMed

    Wasfie, Tarik J; Barber, Kimberly R

    2015-01-01

    Perioperative temperature management is imperative for positive surgical outcomes. This study assessed the clinical and wellbeing benefits of extending normothermia by using a portable warming gown. A total of 94 patients undergoing elective surgery were enrolled. They were randomized pre-operatively to either a portable warming gown or the standard warming procedure. The warming gown stayed with patients from pre-op to operating room to postrecovery room discharge. Core temperature was tracked throughout the study. Patients also provided responses to a satisfaction and comfort status survey. The change in average core temperature did not differ significantly between groups (P = 0.23). A nonsignificant 48% relative decrease in hypothermic events was observed for the extended warming group (P = 0.12). Patients receiving the warming gown were more likely to report always having their temperature controlled (P = 0.04) and significantly less likely to request additional blankets for comfort (P = 0.006). Clinical outcomes and satisfaction were improved for patients with extended warming.

  2. The yeast genome undergoes significant topological reorganization in quiescence

    PubMed Central

    Rutledge, Mark T.; Russo, Mariano; Belton, Jon-Matthew; Dekker, Job; Broach, James R.

    2015-01-01

    We have examined the three-dimensional organization of the yeast genome during quiescence by a chromosome capture technique as a means of understanding how genome organization changes during development. For exponentially growing cells we observe high levels of inter-centromeric interaction but otherwise a predominance of intrachromosomal interactions over interchromosomal interactions, consistent with aggregation of centromeres at the spindle pole body and compartmentalization of individual chromosomes within the nucleoplasm. Three major changes occur in the organization of the quiescent cell genome. First, intrachromosomal associations increase at longer distances in quiescence as compared to growing cells. This suggests that chromosomes undergo condensation in quiescence, which we confirmed by microscopy by measurement of the intrachromosomal distances between two sites on one chromosome. This compaction in quiescence requires the condensin complex. Second, inter-centromeric interactions decrease, consistent with prior data indicating that centromeres disperse along an array of microtubules during quiescence. Third, inter-telomeric interactions significantly increase in quiescence, an observation also confirmed by direct measurement. Thus, survival during quiescence is associated with substantial topological reorganization of the genome. PMID:26202961

  3. Profound bradycardia with decreased PEEP.

    PubMed

    Wilcox, Susan R; Kansagra, Ankit; Richards, Jeremy B

    2013-11-01

    An athletic 21-year-old male was admitted to the surgical ICU after sustaining 2 stab wounds to his torso. He had an episode of left lung collapse early in his course, managed with suctioning and increased PEEP, to 15 cm H2O. He was bradycardic (heart rates 50-60 beats/min) throughout his ICU stay, but when the PEEP was lowered to 5 cm H2O in preparation for extubation, he developed sinus pauses and his heart rate dropped to 20 beats/min. After a thorough evaluation, the drop in his heart rate was determined to be due to increased vagal tone from increased cardiac output with the decreased PEEP. After premedication with glycopyrrolate, he was successfully extubated the following day, while his heart rate remained at his baseline of 50 beats/min. We review the physiologic mechanisms of bradycardia due to the removal of mechanical ventilation.

  4. Hyperhomocysteinemia decreases bone blood flow.

    PubMed

    Tyagi, Neetu; Vacek, Thomas P; Fleming, John T; Vacek, Jonathan C; Tyagi, Suresh C

    2011-01-25

    Elevated plasma levels of homocysteine (Hcy), known as hyperhomocysteinemia (HHcy), are associated with osteoporosis. A decrease in bone blood flow is a potential cause of compromised bone mechanical properties. Therefore, we hypothesized that HHcy decreases bone blood flow and biomechanical properties. To test this hypothesis, male Sprague-Dawley rats were treated with Hcy (0.67 g/L) in drinking water for 8 weeks. Age-matched rats served as controls. At the end of the treatment period, the rats were anesthetized. Blood samples were collected from experimental or control rats. Biochemical turnover markers (body weight, Hcy, vitamin B(12), and folate) were measured. Systolic blood pressure was measured from the right carotid artery. Tibia blood flow was measured by laser Doppler flow probe. The results indicated that Hcy levels were significantly higher in the Hcy-treated group than in control rats, whereas vitamin B(12) levels were lower in the Hcy-treated group compared with control rats. There was no significant difference in folate concentration and blood pressure in Hcy-treated versus control rats. The tibial blood flow index of the control group was significantly higher (0.78 ± 0.09 flow unit) compared with the Hcy-treated group (0.51 ± 0.09). The tibial mass was 1.1 ± 0.1 g in the control group and 0.9 ± 0.1 in the Hcy-treated group. The tibia bone density was unchanged in Hcy-treated rats. These results suggest that Hcy causes a reduction in bone blood flow, which contributes to compromised bone biomechanical properties.

  5. Relative Valuation of Pain in Human Orbitofrontal Cortex

    PubMed Central

    Vlaev, Ivo; Seymour, Ben; Chater, Nick; Dolan, Raymond J.

    2014-01-01

    The valuation of health-related states, including pain, is a critical issue in clinical practice, health economics, and pain neuroscience. Surprisingly the monetary value people associate with pain is highly context-dependent, with participants willing to pay more to avoid medium-level pain when presented in a context of low-intensity, rather than high-intensity, pain. Here, we ask whether context impacts upon the neural representation of pain itself, or alternatively the transformation of pain into valuation-driven behavior. While undergoing fMRI, human participants declared how much money they would be willing to pay to avoid repeated instances of painful cutaneous electrical stimuli delivered to the foot. We also implemented a contextual manipulation that involved presenting medium-level painful stimuli in blocks with either low- or high-level stimuli. We found no evidence of context-dependent activity within a conventional “pain matrix,” where pain-evoked activity reflected absolute stimulus intensity. By contrast, in right lateral orbitofrontal cortex, a strong contextual dependency was evident, and here activity tracked the contextual rank of the pain. The findings are in keeping with an architecture where an absolute pain valuation system and a rank-dependent system interact to influence willing to pay to avoid pain, with context impacting value-based behavior high in a processing hierarchy. This segregated processing hints that distinct neural representations reflect sensory aspects of pain and components that are less directly nociceptive whose integration also guides pain-related actions. A dominance of the latter might account for puzzling phenomena seen in somatization disorders where perceived pain is a dominant driver of behavior. PMID:25355207

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

    PubMed Central

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

    2016-01-01

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

  7. Role of Muscarinic Acetylcholine Receptor-2 in the Cerebellar Cortex in Cardiovascular Modulation in Anaesthetized Rats.

    PubMed

    Zhang, Changzheng; Sun, Tingzhe; Zhou, Peiling; Zhu, Qingfeng; Zhang, Liefeng

    2016-04-01

    Our previous investigations have demonstrated that microinjection of acetylcholine (ACh) or muscarinic ACh receptor activation in the cerebellar cortex induces a systemic blood pressure depressor response. This study aimed to determine the role of muscarinic ACh receptor-2 (M2 receptor) in the cerebellar cortex in cardiovascular function regulation in rats. A nonselective muscarinic receptor agonist (oxotremorine M, OXO; 30 mM), a selective M2 receptor agonist (arecaidine but-2-ynyl ester tosylate, ABET; 3, 10, and 30 mM), 30 mM OXO mixed with a selective M2 receptor antagonist (methoctramine hydrate, MCT; 0.3, 1, and 3 mM), and normal saline (0.9 % NaCl) were separately microinjected (0.5 µl/5 s) into the cerebellar cortex (lobule VI) of anaesthetized rats. We measured the mean arterial pressure (MAP), maximum change in MAP, and reactive time (RT; the duration required for the blood pressure to return to basal levels), heart rate (HR) and the maximum change in HR during the RT in response to drug activation. The results demonstrated that ABET dose-dependently decreased MAP and HR, increased the maximum change in MAP and the maximum change in HR, and prolonged the RT. Furthermore, MCT dose-dependently blocked the OXO-mediated cardiovascular depressor response. This study provides the first evidence that M2 receptors in the cerebellar cortex are involved in cardiovascular regulation, the activation of which evokes significant depressor and bradycardic responses.

  8. Changes in thickness and surface area of the human cortex and their relationship with intelligence.

    PubMed

    Schnack, Hugo G; van Haren, Neeltje E M; Brouwer, Rachel M; Evans, Alan; Durston, Sarah; Boomsma, Dorret I; Kahn, René S; Hulshoff Pol, Hilleke E

    2015-06-01

    Changes in cortical thickness over time have been related to intelligence, but whether changes in cortical surface area are related to general cognitive functioning is unknown. We therefore examined the relationship between intelligence quotient (IQ) and changes in cortical thickness and surface over time in 504 healthy subjects. At 10 years of age, more intelligent children have a slightly thinner cortex than children with a lower IQ. This relationship becomes more pronounced with increasing age: with higher IQ, a faster thinning of the cortex is found over time. In the more intelligent young adults, this relationship reverses so that by the age of 42 a thicker cortex is associated with higher intelligence. In contrast, cortical surface is larger in more intelligent children at the age of 10. The cortical surface is still expanding, reaching its maximum area during adolescence. With higher IQ, cortical expansion is completed at a younger age; and once completed, surface area decreases at a higher rate. These findings suggest that intelligence may be more related to the magnitude and timing of changes in brain structure during development than to brain structure per se, and that the cortex is never completed but shows continuing intelligence-dependent development.

  9. Contralateral somatosensory neglect in unrestrained rats after lesion of the parietal cortex of the left hemisphere.

    PubMed

    Holm, S; Mogensen, J

    1993-01-01

    Three groups of rats were studied: a sham operated control group and two groups in which the parietal "association" cortex had been ablated in the left and right hemispheres respectively. Twenty-four hours and 8 days postoperatively the animals were subjected to a test in which their responsiveness to lateralized somatosensory stimuli was measured while the rats were left unrestrained. Additionally, an activity cage locomotion test followed immediately upon both tests of somatosensory responsiveness. Twenty-four hours postoperatively the animals in which the parietal cortex of the left hemisphere had been ablated demonstrated a significant contralateral neglect of somatosensory stimuli while the group in which the right parietal cortex had been ablated only exhibited a non-significant tendency to a contralateral neglect. While the activity cage test did not reveal an overall difference in the activity level of the three groups the latency to initiate locomotion in the activity cage was found to be significantly decreased in both ablated groups. Eight days postoperatively both ablated groups appeared fully recovered. It is concluded that ablations of the parietal "association" cortex of the rat are associated with a syndrome of contralateral somatosensory neglect that can even be demonstrated if the animals are left unrestrained during testing.

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

    PubMed

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

    2016-04-01

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

  11. Motor cortex activation in Parkinson's disease: dissociation of electrocortical and peripheral measures of response generation.

    PubMed

    Praamstra, P; Plat, E M; Meyer, A S; Horstink, M W

    1999-09-01

    This study investigated characteristics of motor cortex activation and response generation in Parkinson's disease with measures of electrocortical activity (lateralized readiness potential [LRP]), electromyographic activity (EMG), and isometric force in a noise-compatibility task. When presented with stimuli consisting of incompatible target and distractor elements asking for responses of opposite hands, patients were less able than control subjects to suppress activation of the motor cortex controlling the wrong response hand. This was manifested in the pattern of reaction times and in an incorrect lateralization of the LRP. Onset latency and rise time of the LRP did not differ between patients and control subjects, but EMG and response force developed more slowly in patients. Moreover, in patients but not in control subjects, the rate of development of EMG and response force decreased as reaction time increased. We hypothesize that this dissociation between electrocortical activity and peripheral measures in Parkinson's disease is the result of changes in motor cortex function that alter the relation between signal-related and movement-related neural activity in the motor cortex. In the LRP, this altered balance may obscure an abnormal development of movement-related neural activity.

  12. Coenzyme Q10 Abrogated the 28 Days Aluminium Chloride Induced Oxidative Changes in Rat Cerebral Cortex

    PubMed Central

    Majumdar, Anuradha S.; Nirwane, Abhijit; Kamble, Rahul

    2014-01-01

    Objective: The present study was designed to elucidate the impact of oral administration of aluminium chloride for 28 days with respect to oxidative stress in the cerebral cortex of female rats. Further, to investigate the potentials of Coenzyme (Co) Q10 (4, 8, and 12 mg/kg, i.p.) in mitigating the detrimental changes. Materials and Methods: Biochemical estimations of cerebral lipid peroxidation (LPO), reduced glutathione (GSH), vitamin E and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were carried out after 28 days of aluminium chloride (AlCl3) and Co Q10 exposures along with histopathological examination of cerebral cortex of the rats. Results: Subacute exposure to AlCl3(5 mg/kg) led to significant decrease in levels of GSH, vitamin E and activities of SOD, CAT, GPx, and an increase in LPO of cerebral cortex. These aberrations were restored by Co Q10 (12 mg/kg, i.p.). This protection offered was comparable to that of L-deprenyl (1 mg/kg, i.p.) which served as a reference standard. Histopathological evaluations confirmed that the normal cerebral morphology was maintained by Co Q10. Conclusion: Thus, AlCl3 exposure hampers the activities of various antioxidant enzymes and induces oxidative stress in cerebral cortex of female Wistar rats. Supplementation with intraperitoneal Co Q10 abrogated these deleterious effects of AlCl3. PMID:25253934

  13. Contributions of diverse excitatory and inhibitory neurons to recurrent network activity in cerebral cortex.

    PubMed

    Neske, Garrett T; Patrick, Saundra L; Connors, Barry W

    2015-01-21

    The recurrent synaptic architecture of neocortex allows for self-generated network activity. One form of such activity is the Up state, in which neurons transiently receive barrages of excitatory and inhibitory synaptic inputs that depolarize many neurons to spike threshold before returning to a relatively quiescent Down state. The extent to which different cell types participate in Up states is still unclear. Inhibitory interneurons have particularly diverse intrinsic properties and synaptic connections with the local network, suggesting that different interneurons might play different roles in activated network states. We have studied the firing, subthreshold behavior, and synaptic conductances of identified cell types during Up and Down states in layers 5 and 2/3 in mouse barrel cortex in vitro. We recorded from pyramidal cells and interneurons expressing parvalbumin (PV), somatostatin (SOM), vasoactive intestinal peptide (VIP), or neuropeptide Y. PV cells were the most active interneuron subtype during the Up state, yet the other subtypes also received substantial synaptic conductances and often generated spikes. In all cell types except PV cells, the beginning of the Up state was dominated by synaptic inhibition, which decreased thereafter; excitation was more persistent, suggesting that inhibition is not the dominant force in terminating Up states. Compared with barrel cortex, SOM and VIP cells were much less active in entorhinal cortex during Up states. Our results provide a measure of functional connectivity of various neuron types in barrel cortex and suggest differential roles for interneuron types in the generation and control of persistent network activity.

  14. Contextual Modulation is Related to Efficiency in a Spiking Network Model of Visual Cortex

    PubMed Central

    Sharifian, Fariba; Heikkinen, Hanna; Vigário, Ricardo; Vanni, Simo

    2016-01-01

    In the visual cortex, stimuli outside the classical receptive field (CRF) modulate the neural firing rate, without driving the neuron by themselves. In the primary visual cortex (V1), such contextual modulation can be parametrized with an area summation function (ASF): increasing stimulus size causes first an increase and then a decrease of firing rate before reaching an asymptote. Earlier work has reported increase of sparseness when CRF stimulation is extended to its surroundings. However, there has been no clear connection between the ASF and network efficiency. Here we aimed to investigate possible link between ASF and network efficiency. In this study, we simulated the responses of a biomimetic spiking neural network model of the visual cortex to a set of natural images. We varied the network parameters, and compared the V1 excitatory neuron spike responses to the corresponding responses predicted from earlier single neuron data from primate visual cortex. The network efficiency was quantified with firing rate (which has direct association to neural energy consumption), entropy per spike and population sparseness. All three measures together provided a clear association between the network efficiency and the ASF. The association was clear when varying the horizontal connectivity within V1, which influenced both the efficiency and the distance to ASF, DAS. Given the limitations of our biophysical model, this association is qualitative, but nevertheless suggests that an ASF-like receptive field structure can cause efficient population response. PMID:26834619

  15. Assessing the Effect of Early Visual Cortex Transcranial Magnetic Stimulation on Working Memory Consolidation.

    PubMed

    van Lamsweerde, Amanda E; Johnson, Jeffrey S

    2017-03-02

    Maintaining visual working memory (VWM) representations recruits a network of brain regions, including the frontal, posterior parietal, and occipital cortices; however, it is unclear to what extent the occipital cortex is engaged in VWM after sensory encoding is completed. Noninvasive brain stimulation data show that stimulation of this region can affect working memory (WM) during the early consolidation time period, but it remains unclear whether it does so by influencing the number of items that are stored or their precision. In this study, we investigated whether single-pulse transcranial magnetic stimulation (spTMS) to the occipital cortex during VWM consolidation affects the quantity or quality of VWM representations. In three experiments, we disrupted VWM consolidation with either a visual mask or spTMS to retinotopic early visual cortex. We found robust masking effects on the quantity of VWM representations up to 200 msec poststimulus offset and smaller, more variable effects on WM quality. Similarly, spTMS decreased the quantity of VWM representations, but only when it was applied immediately following stimulus offset. Like visual masks, spTMS also produced small and variable effects on WM precision. The disruptive effects of both masks and TMS were greatly reduced or entirely absent within 200 msec of stimulus offset. However, there was a reduction in swap rate across all time intervals, which may indicate a sustained role of the early visual cortex in maintaining spatial information.

  16. Effects of static magnetic field and cadmium on oxidative stress and DNA damage in rat cortex brain and hippocampus.

    PubMed

    Amara, Salem; Douki, Thierry; Garrel, Catherine; Favier, Alain; Ben Rhouma, Khémais; Sakly, Mohsen; Abdelmelek, Hafedh

    2011-03-01

    The present study was undertaken to determine the effect of co-exposure to static magnetic field (SMF) and cadmium (Cd) on the antioxidant enzymes activity and DNA integrity in rat brain. Sub-chronic exposure to CdCl (CdCl(2), 40 mg/L, per os) for 30 days resulted in a significant reduction in antioxidant enzyme activity such as the glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) in frontal cortex and hippocampus. Total GSH were decreased in the frontal cortex of the Cd-exposed group. Cd exposure induced an increase in malondialdehyde (MDA) concentration in the frontal cortex and hippocampus. Moreover, the same exposure increased 8-oxo-7,8-dihydro-2-desoxyguanosine (8-oxodGuo) level in rat brain. Interestingly, the combined effect of SMF (128 mT, 1 hour/day for 30 consecutive days) and CdCl (40 mg/L, per os) decreased the SOD activity and glutathione level in frontal cortex as compared with the Cd group. Moreover, the association between SMF and Cd increased MDA concentration in frontal cortex as compared with Cd-exposed rats. DNA analysis revealed that SMF exposure failed to alter 8-oxodGuo concentration in Cd-exposed rats. Our data showed that Cd exposure altered the antioxidant enzymes activity and induced oxidative DNA lesions in rat brain. The combined effect of SMF and Cd increased oxidative damage in rat brain as compared with Cd-exposed rats.

  17. Influence of body temperature on the evoked activity in mouse visual cortex.

    PubMed

    Tang, Bin; Kalatsky, Valery A

    2013-06-01

    Optical imaging of intrinsic signals and conventional electrophysiological methods were used to investigate the correlation between the evoked activity in mouse visual cortex and core body temperature. The results show that hypothermia (25-36 °C) decreases the intensity of optical imaging in the visual cortex and the imaging signal reversibly disappears at 25 °C. Hyperthermia (39-41 °C) increases the intensity but decreases the quality of cortical imaging when body temperature is above 40 °C. The change of optical imaging was in line with that of neuronal activities and local field potentials (LFPs) directly recorded from the visual cortex at 25-39 °C. Hypothermia decreases neuron firing rate and LFPs amplitude. Most of the recorded neurons ceased firing to visual stimulation at 25 °C. Hyperthermia increases neuronal firing rate and LFPs amplitude. Both are reduced when body temperature is above 40 °C, though neither change was statistically significant. These results suggest: (1) Body temperature has an important impact on the visual cortical evoked activities and optical imaging generally reflects these effects when body temperature is between 25 and 39 °C; (2) Optical imaging may not properly reflect the neuronal activity when body temperature is over 40 °C. It is important to maintain core body temperature within 3 °C of the normal body temperature to obtain verifiable results.

  18. Nursing Strategies for Patients with Chronic Renal Failure Undergoing Maintenance Hemodialysis Treatment by Arteriovenous Fistula

    PubMed Central

    QIN, Hong Yan; JIA, Ping; LIU, Hui

    2016-01-01

    Background: We aimed to analyze the effect of nursing strategies on patients with chronic renal failure (CRF) undergoing maintenance hemodialysis (MHD) treatment by puncturing on arteriovenous fistula (AVF). Methods: Ninety-two patients with chronic renal failure undergoing maintenance hemodialysis (MHD) between Jan 2014 and Jan 2015 were included in the study (all undergoing AVF, dialysis for 2–3 sessions per week, 4–5 h per session) and randomly divided into control group and observation group. Patients in control group were given standard nursing care and patients in observation group were given professional nursing of internal fistula. The complication rate and dysfunction rate during internal fistula perioperative period, fistula usage time and effect on life quality of patients of these two groups were compared (during 18-month follow-up). Results: The complication rate and dysfunction rate during internal fistula perioperative period of the observation group were significantly lower than that of the control group, and the difference was statistically significant (P<0.05). The median time of internal fistula usage was significantly prolonged, and the health index, emotion index and psychology index quality-of-life in the observation group were significantly higher than that of the control group (P<0.05). Conclusion: Professional nursing strategies of internal fistula can prolong service time, decrease complications and improve life quality for patients undergoing maintenance hemodialysis treatment via arteriovenous fistula. PMID:27957433

  19. Epigenetic dysregulation in the developing Down syndrome cortex

    PubMed Central

    El Hajj, Nady; Dittrich, Marcus; Böck, Julia; Kraus, Theo F. J.; Nanda, Indrajit; Müller, Tobias; Seidmann, Larissa; Tralau, Tim; Galetzka, Danuta; Schneider, Eberhard; Haaf, Thomas

    2016-01-01

    ABSTRACT Using Illumina 450K arrays, 1.85% of all analyzed CpG sites were significantly hypermethylated and 0.31% hypomethylated in fetal Down syndrome (DS) cortex throughout the genome. The methylation changes on chromosome 21 appeared to be balanced between hypo- and hyper-methylation, whereas, consistent with prior reports, all other chromosomes showed 3–11 times more hyper- than hypo-methylated sites. Reduced NRSF/REST expression due to upregulation of DYRK1A (on chromosome 21q22.13) and methylation of REST binding sites during early developmental stages may contribute to this genome-wide excess of hypermethylated sites. Upregulation of DNMT3L (on chromosome 21q22.4) could lead to de novo methylation in neuroprogenitors, which then persists in the fetal DS brain where DNMT3A and DNMT3B become downregulated. The vast majority of differentially methylated promoters and genes was hypermethylated in DS and located outside chromosome 21, including the protocadherin gamma (PCDHG) cluster on chromosome 5q31, which is crucial for neural circuit formation in the developing brain. Bisulfite pyrosequencing and targeted RNA sequencing showed that several genes of PCDHG subfamilies A and B are hypermethylated and transcriptionally downregulated in fetal DS cortex. Decreased PCDHG expression is expected to reduce dendrite arborization and growth in cortical neurons. Since constitutive hypermethylation of PCDHG and other genes affects multiple tissues, including blood, it may provide useful biomarkers for DS brain development and pharmacologic targets for therapeutic interventions. PMID:27245352

  20. 14 CFR 204.5 - Certificated and commuter air carriers undergoing or proposing to undergo substantial change in...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... undergoing or proposing to undergo substantial change in operations, ownership, or management. 204.5 Section..., ownership, or management. (a) A certificated or commuter air carrier proposing a substantial change in... operations, management, or ownership, including changes that may affect the air carrier's citizenship,...

  1. 14 CFR 204.5 - Certificated and commuter air carriers undergoing or proposing to undergo substantial change in...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... undergoing or proposing to undergo substantial change in operations, ownership, or management. 204.5 Section..., ownership, or management. (a) A certificated or commuter air carrier proposing a substantial change in... operations, management, or ownership, including changes that may affect the air carrier's citizenship,...

  2. Knots cascade detected by a monotonically decreasing sequence of values

    PubMed Central

    Liu, Xin; Ricca, Renzo L.

    2016-01-01

    Due to reconnection or recombination of neighboring strands superfluid vortex knots and DNA plasmid torus knots and links are found to undergo an almost identical cascade process, that tend to reduce topological complexity by stepwise unlinking. Here, by using the HOMFLYPT polynomial recently introduced for fluid knots, we prove that under the assumption that topological complexity decreases by stepwise unlinking this cascade process follows a path detected by a unique, monotonically decreasing sequence of numerical values. This result holds true for any sequence of standardly embedded torus knots T(2, 2n + 1) and torus links T(2, 2n). By this result we demonstrate that the computation of this adapted HOMFLYPT polynomial provides a powerful tool to measure topological complexity of various physical systems. PMID:27052386

  3. Knots cascade detected by a monotonically decreasing sequence of values

    NASA Astrophysics Data System (ADS)

    Liu, Xin; Ricca, Renzo L.

    2016-04-01

    Due to reconnection or recombination of neighboring strands superfluid vortex knots and DNA plasmid torus knots and links are found to undergo an almost identical cascade process, that tend to reduce topological complexity by stepwise unlinking. Here, by using the HOMFLYPT polynomial recently introduced for fluid knots, we prove that under the assumption that topological complexity decreases by stepwise unlinking this cascade process follows a path detected by a unique, monotonically decreasing sequence of numerical values. This result holds true for any sequence of standardly embedded torus knots T(2, 2n + 1) and torus links T(2, 2n). By this result we demonstrate that the computation of this adapted HOMFLYPT polynomial provides a powerful tool to measure topological complexity of various physical systems.

  4. The basic nonuniformity of the cerebral cortex

    PubMed Central

    Herculano-Houzel, Suzana; Collins, Christine E.; Wong, Peiyan; Kaas, Jon H.; Lent, Roberto

    2008-01-01

    Evolutionary changes in the size of the cerebral cortex, a columnar structure, often occur through the addition or subtraction of columnar modules with the same number of neurons underneath a unit area of cortical surface. This view is based on the work of Rockel et al. [Rockel AJ, Hiorns RW, Powell TP (1980) The basic uniformity in structure of the neocortex. Brain 103:221–244], who found a steady number of approximately 110 neurons underneath a surface area of 750 μm2 (147,000 underneath 1 mm2) of the cerebral cortex of five species from different mammalian orders. These results have since been either corroborated or disputed by different groups. Here, we show that the number of neurons underneath 1 mm2 of the cerebral cortical surface of nine primate species and the closely related Tupaia sp. is not constant and varies by three times across species. We found that cortical thickness is not inversely proportional to neuronal density across species and that total cortical surface area increases more slowly than, rather than linearly with, the number of neurons underneath it. The number of neurons beneath a unit area of cortical surface varies linearly with neuronal density, a parameter that is neither related to cortical size nor total number of neurons. Our finding of a variable number of neurons underneath a unit area of the cerebral cortex across primate species indicates that models of cortical organization cannot assume that cortical columns in different primates consist of invariant numbers of neurons. PMID:18689685

  5. Retinotopic Organization of Human Ventral Visual Cortex

    PubMed Central

    Arcaro, Michael J.; McMains, Stephanie A.; Singer, Benjamin D.; Kastner, Sabine

    2009-01-01

    Functional magnetic resonance imaging (fMRI) studies have shown that human ventral visual cortex anterior to area hV4 contains two visual field maps, VO-1 and VO-2, that together form the VO-cluster (Brewer et al., 2005). This cluster is characterized by common functional response properties and responds preferentially to color and object stimuli. Here, we confirm the topographic and functional characteristics of the VO-cluster and describe two new visual field maps that are located anterior to VO-2 extending across the collateral sulcus into the posterior parahippocampal cortex (PHC). We refer to these visual field maps as parahippocampal areas PHC-1 and PHC-2. Each PHC map contains a topographic representation of contralateral visual space. The polar angle representation in PHC-1 extends from regions near the lower vertical meridian (that is the shared border with VO-2) to those close to the upper vertical meridian (that is the shared border with PHC-2). The polar angle representation in PHC-2 is a mirror-reversal of the PHC-1 representation. PHC-1 and PHC-2 share a foveal representation and show a strong bias towards representations of peripheral eccentricities. Both the foveal and peripheral representations of PHC-1 and PHC-2 respond more strongly to scenes than to objects or faces, with greater scene preference in PHC-2 than PHC-1. Importantly, both areas heavily overlap with the functionally defined parahippocampal place area (PPA). Our results suggest that ventral visual cortex can be subdivided on the basis of topographic criteria into a greater number of discrete maps than previously thought. PMID:19710316

  6. Inhibition by Somatostatin Interneurons in Olfactory Cortex

    PubMed Central

    Large, Adam M.; Kunz, Nicholas A.; Mielo, Samantha L.; Oswald, Anne-Marie M.

    2016-01-01

    Inhibitory circuitry plays an integral role in cortical network activity. The development of transgenic mouse lines targeting unique interneuron classes has significantly advanced our understanding of the functional roles of specific inhibitory circuits in neocortical sensory processing. In contrast, considerably less is known about the circuitry and function of interneuron classes in piriform cortex, a paleocortex responsible for olfactory processing. In this study, we sought to utilize transgenic technology to investigate inhibition mediated by somatostatin (SST) interneurons onto pyramidal cells (PCs), parvalbumin (PV) interneurons, and other interneuron classes. As a first step, we characterized the anatomical distributions and intrinsic properties of SST and PV interneurons in four transgenic lines (SST-cre, GIN, PV-cre, and G42) that are commonly interbred to investigate inhibitory connectivity. Surprisingly, the distributions SST and PV cell subtypes targeted in the GIN and G42 lines were sparse in piriform cortex compared to neocortex. Moreover, two-thirds of interneurons recorded in the SST-cre line had electrophysiological properties similar to fast spiking (FS) interneurons rather than regular (RS) or low threshold spiking (LTS) phenotypes. Nonetheless, like neocortex, we find that SST-cells broadly inhibit a number of unidentified interneuron classes including putatively identified PV cells and surprisingly, other SST cells. We also confirm that SST-cells inhibit pyramidal cell dendrites and thus, influence dendritic integration of afferent and recurrent inputs to the piriform cortex. Altogether, our findings suggest that SST interneurons play an important role in regulating both excitation and the global inhibitory network during olfactory processing. PMID:27582691

  7. Apraxia, pantomime and the parietal cortex.

    PubMed

    Niessen, E; Fink, G R; Weiss, P H

    2014-01-01

    Apraxia, a disorder of higher motor cognition, is a frequent and outcome-relevant sequel of left hemispheric stroke. Deficient pantomiming of object use constitutes a key symptom of apraxia and is assessed when testing for apraxia. To date the neural basis of pantomime remains controversial. We here review the literature and perform a meta-analysis of the relevant structural and functional imaging (fMRI/PET) studies. Based on a systematic literature search, 10 structural and 12 functional imaging studies were selected. Structural lesion studies associated pantomiming deficits with left frontal, parietal and temporal lesions. In contrast, functional imaging studies associate pantomimes with left parietal activations, with or without concurrent frontal or temporal activations. Functional imaging studies that selectively activated parietal cortex adopted the most stringent controls. In contrast to previous suggestions, current analyses show that both lesion and functional studies support the notion of a left-hemispheric fronto-(temporal)-parietal network underlying pantomiming object use. Furthermore, our review demonstrates that the left parietal cortex plays a key role in pantomime-related processes. More specifically, stringently controlled fMRI-studies suggest that in addition to storing motor schemas, left parietal cortex is also involved in activating these motor schemas in the context of pantomiming object use. In addition to inherent differences between structural and functional imaging studies and consistent with the dedifferentiation hypothesis, the age difference between young healthy subjects (typically included in functional imaging studies) and elderly neurological patients (typically included in structural lesion studies) may well contribute to the finding of a more distributed representation of pantomiming within the motor-dominant left hemisphere in the elderly.

  8. Identification of cortex in magnetic resonance images

    NASA Astrophysics Data System (ADS)

    VanMeter, John W.; Sandon, Peter A.

    1992-06-01

    The overall goal of the work described here is to make available to the neurosurgeon in the operating room an on-line, three-dimensional, anatomically labeled model of the patient brain, based on pre-operative magnetic resonance (MR) images. A stereotactic operating microscope is currently in experimental use, which allows structures that have been manually identified in MR images to be made available on-line. We have been working to enhance this system by combining image processing techniques applied to the MR data with an anatomically labeled 3-D brain model developed from the Talairach and Tournoux atlas. Here we describe the process of identifying cerebral cortex in the patient MR images. MR images of brain tissue are reasonably well described by material mixture models, which identify each pixel as corresponding to one of a small number of materials, or as being a composite of two materials. Our classification algorithm consists of three steps. First, we apply hierarchical, adaptive grayscale adjustments to correct for nonlinearities in the MR sensor. The goal of this preprocessing step, based on the material mixture model, is to make the grayscale distribution of each tissue type constant across the entire image. Next, we perform an initial classification of all tissue types according to gray level. We have used a sum of Gaussian's approximation of the histogram to perform this classification. Finally, we identify pixels corresponding to cortex, by taking into account the spatial patterns characteristic of this tissue. For this purpose, we use a set of matched filters to identify image locations having the appropriate configuration of gray matter (cortex), cerebrospinal fluid and white matter, as determined by the previous classification step.

  9. An integrator circuit in cerebellar cortex.

    PubMed

    Maex, Reinoud; Steuber, Volker

    2013-09-01

    The brain builds dynamic models of the body and the outside world to predict the consequences of actions and stimuli. A well-known example is the oculomotor integrator, which anticipates the position-dependent elasticity forces acting on the eye ball by mathematically integrating over time oculomotor velocity commands. Many models of neural integration have been proposed, based on feedback excitation, lateral inhibition or intrinsic neuronal nonlinearities. We report here that a computational model of the cerebellar cortex, a structure thought to implement dynamic models, reveals a hitherto unrecognized integrator circuit. In this model, comprising Purkinje cells, molecular layer interneurons and parallel fibres, Purkinje cells were able to generate responses lasting more than 10 s, to which both neuronal and network mechanisms contributed. Activation of the somatic fast sodium current by subthreshold voltage fluctuations was able to maintain pulse-evoked graded persistent activity, whereas lateral inhibition among Purkinje cells via recurrent axon collaterals further prolonged the responses to step and sine wave stimulation. The responses of Purkinje cells decayed with a time-constant whose value depended on their baseline spike rate, with integration vanishing at low (< 1 per s) and high rates (> 30 per s). The model predicts that the apparently fast circuit of the cerebellar cortex may control the timing of slow processes without having to rely on sensory feedback. Thus, the cerebellar cortex may contain an adaptive temporal integrator, with the sensitivity of integration to the baseline spike rate offering a potential mechanism of plasticity of the response time-constant.

  10. Connectivity Changes Underlying Neurofeedback Training of Visual Cortex Activity

    PubMed Central

    Scharnowski, Frank; Rosa, Maria Joao; Golestani, Narly; Hutton, Chloe; Josephs, Oliver

    2014-01-01

    Neurofeedback based on real-time functional magnetic resonance imaging (fMRI) is a new approach that allows training of voluntary control over regionally specific brain activity. However, the neural basis of successful neurofeedback learning remains poorly understood. Here, we assessed changes in effective brain connectivity associated with neurofeedback training of visual cortex activity. Using dynamic causal modeling (DCM), we found that training participants to increase visual cortex activity was associated with increased effective connectivity between the visual cortex and the superior parietal lobe. Specifically, participants who learned to control activity in their visual cortex showed increased top-down control of the superior parietal lobe over the visual cortex, and at the same time reduced bottom-up processing. These results are consistent with efficient employment of top-down visual attention and imagery, which were the cognitive strategies used by participants to increase their visual cortex activity. PMID:24609065

  11. The management of patients with atrial fibrillation undergoing percutaneous coronary intervention with stent implantation: in-hospital-data from the Atrial Fibrillation undergoing Coronary Artery Stenting study.

    PubMed

    Schlitt, Axel; Rubboli, Andrea; Lip, Gregory Y H; Lahtela, Heli; Valencia, Josè; Karjalainen, Pasi P; Weber, Michael; Laine, Mika; Kirchhof, Paulus; Niemelä, Matti; Vikman, Saila; Buerke, Michael; Airaksinen, K E Juhani

    2013-12-01

    Current recommendations on the management of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention with stent (PCI-S) essentially derive from small, single-center, retrospective datasets. To obtain larger and better quality data, we carried out the prospective, multicenter Atrial Fibrillation undergoing Coronary Artery Stenting (AFCAS) study. Therefore, consecutive patients with history of or ongoing AF undergoing PCI-S were enrolled, and occurrence of adverse ischemic and bleeding events recorded during 12 months follow-up. In this article, we report the in-hospital observations. Out of the 963 patients, in the majority of cases (49.1%) AF was permanent. The associated risk of stroke, as defined by a CHADS2 -score ≥2, was in 70% of patients moderate to high. Upon enrollment in the registry, 69.3% of patients were on VKA therapy. Overall occurrence of in-hospital major adverse cardiac events was 4.5% (cardiovascular death 1.9%, urgent revascularization in 1.5%, and stroke/arterial thromboembolism in 0.6%). Bleeding complications occurred in 7.1% of patients, being severe in 2.5%. In a logistic regression analysis, no risk factor was independently associated with bleeding events, whereas Clopidogrel treatment decreased and female gender/treatment with gpIIb/IIIa-antagonists, respectively increased the risk for the combined ischemic endpoint. The majority of AF patients undergoing PCI-S are at high stroke risk, and therefore VKA treatment should not be withdrawn and combined anticoagulant and antiplatelet treatment is warranted. Current management appears largely in accordance with current recommendations, whereby accounting for the limited occurrence of in-hospital adverse ischemic and bleeding events.

  12. Estrogen receptor-alpha gene expression in the cortex: sex differences during development and in adulthood.

    PubMed

    Wilson, Melinda E; Westberry, Jenne M; Trout, Amanda L

    2011-03-01

    17β-estradiol is a hormone with far-reaching organizational, activational and protective actions in both male and female brains. The organizational effects of early estrogen exposure are essential for long-lasting behavioral and cognitive functions. Estradiol mediates many of its effects through the intracellular receptors, estrogen receptor-alpha (ERα) and estrogen receptor-beta (ERβ). In the rodent cerebral cortex, estrogen receptor expression is high early in postnatal life and declines dramatically as the animal approaches puberty. This decline is accompanied by decreased expression of ERα mRNA. This change in expression is the same in both males and females in the developing isocortex and hippocampus. An understanding of the molecular mechanisms involved in the regulation of estrogen receptor alpha (ERα) gene expression is critical for understanding the developmental, as well as changes in postpubertal expression of the estrogen receptor. One mechanism of suppressing gene expression is by the epigenetic modification of the promoter regions by DNA methylation that results in gene silencing. The decrease in ERα mRNA expression during development is accompanied by an increase in promoter methylation. Another example of regulation of ERα gene expression in the adult cortex is the changes that occur following neuronal injury. Many animal studies have demonstrated that the endogenous estrogen, 17β-estradiol, is neuroprotective. Specifically, low levels of estradiol protect the cortex from neuronal death following middle cerebral artery occlusion (MCAO). In females, this protection is mediated through an ERα-dependent mechanism. ERα expression is rapidly increased following MCAO in females, but not in males. This increase is accompanied by a decrease in methylation of the promoter suggesting a return to the developmental program of gene expression within neurons. Taken together, during development and in adulthood, regulation of ERα gene expression in the

  13. Fulminant hepatic failure in rats induces oxidative stress differentially in cerebral cortex, cerebellum and pons medulla.

    PubMed

    Sathyasaikumar, K V; Swapna, I; Reddy, P V B; Murthy, Ch R K; Dutta Gupta, A; Senthilkumaran, B; Reddanna, P

    2007-03-01

    Hepatic Encephalopathy (HE) is one of the most common complications of acute liver diseases and is known to have profound influence on the brain. Most of the studies, available from the literature are pertaining to whole brain homogenates or mitochondria. Since brain is highly heterogeneous with functions localized in specific areas, the present study was aimed to assess the oxidative stress in different regions of brain-cerebral cortex, cerebellum and pons medulla during acute HE. Acute liver failure was induced in 3-month old adult male Wistar rats by intraperitoneal injection of thioacetamide (300 mg/kg body weight for two days), a well known hepatotoxin. Oxidative stress conditions were assessed by free radical production, lipid peroxidation, nitric oxide levels, GSH/GSSG ratio and antioxidant enzyme machinery in three distinct structures of rat braincerebral cortex, cerebellum and pons medulla. Results of the present study indicate a significant increase in malondialdehyde (MDA) levels, reactive oxygen species (ROS), total nitric oxide levels [(NO) estimated by measuring (nitrites + nitrates)] and a decrease in GSH/GSSG ratio in all the regions of brain. There was also a marked decrease in the activity of the antioxidant enzymes-glutathione peroxidase, glutathione reductase and catalase while the super oxide dismutase activity (SOD) increased. However, the present study also revealed that pons medulla and cerebral cortex were more susceptible to oxidative stress than cerebellum. The increased vulnerability to oxidative stress in pons medulla could be due to the increased NO levels and increased activity of SOD and decreased glutathione peroxidase and glutathione reductase activities. In summary, the present study revealed that oxidative stress prevails in different cerebral regions analyzed during thioacetamide-induced acute liver failure with more pronounced effects on pons medulla and cerebral cortex.

  14. Effect of the environment on the dendritic morphology of the rat auditory cortex.

    PubMed

    Bose, Mitali; Muñoz-Llancao, Pablo; Roychowdhury, Swagata; Nichols, Justin A; Jakkamsetti, Vikram; Porter, Benjamin; Byrapureddy, Rajasekhar; Salgado, Humberto; Kilgard, Michael P; Aboitiz, Francisco; Dagnino-Subiabre, Alexies; Atzori, Marco

    2010-02-01

    The present study aimed to identify morphological correlates of environment-induced changes at excitatory synapses of the primary auditory cortex (A1). We used the Golgi-Cox stain technique to compare pyramidal cells dendritic properties of Sprague-Dawley rats exposed to different environmental manipulations. Sholl analysis, dendritic length measures, and spine density counts were used to monitor the effects of sensory deafness and an auditory version of environmental enrichment (EE). We found that deafness decreased apical dendritic length leaving basal dendritic length unchanged, whereas EE selectively increased basal dendritic length without changing apical dendritic length. On the contrary, deafness decreased while EE increased spine density in both basal and apical dendrites of A1 Layer 2/3 (LII/III) neurons. To determine whether stress contributed to the observed morphological changes in A1, we studied neural morphology in a restraint-induced model that lacked behaviorally relevant acoustic cues. We found that stress selectively decreased apical dendritic length in the auditory but not in the visual primary cortex. Similar to the acoustic manipulation, stress-induced changes in dendritic length possessed a layer-specific pattern displaying LII/III neurons from stressed animals with normal apical dendrites but shorter basal dendrites, while infragranular neurons (Layers V and VI) displayed shorter apical dendrites but normal basal dendrites. The same treatment did not induce similar changes in the visual cortex, demonstrating that the auditory cortex is an exquisitely sensitive target of neocortical plasticity, and that prolonged exposure to different acoustic as well as emotional environmental manipulation may produce specific changes in dendritic shape and spine density.

  15. Vestibular projections in the human cortex.

    PubMed

    de Waele, C; Baudonnière, P M; Lepecq, J C; Tran Ba Huy, P; Vidal, P P

    2001-12-01

    There is considerable evidence from studies on cats and monkeys that several cortical areas such as area 2v at the tip of the intraparietal sulcus, area 3av in the sulcus centralis, the parietoinsular vestibular cortex adjacent to the posterior insula (PIVC) and area 7 in the inferior parietal lobule are involved in the processing of vestibular information. Microelectrode recordings from these areas have shown that: (1) most of these cortical neurons are connected trisynaptically to the labyrinthine endorgans and (2) they receive converging vestibular, visual and somatosensory inputs. These data suggest that a multimodal cortical system is involved in postural and gaze control. In humans, recent positron emission tomography (PET) scans and functional magnetic resonance imaging (fMRI) studies have largely confirmed these data. However, because of the limited temporal resolution of these two methods, the minimum time of arrival of labyrinthine inputs from the vestibular hair cells to these cortical areas has not yet been determined. In this study, we used the evoked potential method to attempt to answer this question. Due to its excellent temporal resolution, this method is ideal for the investigation of the tri- or polysynaptic nature of the vestibulocortical pathways. Eleven volunteer patients, who underwent a vestibular neurectomy due to intractable Meniere's disease (MD) or acoustic neurinoma resection, were included in this experiment. Patients were anesthetized and the vestibular nerve was electrically stimulated. The evoked potentials were recorded by 30 subcutaneous active electrodes located on the scalp. The brain electrical source imaging (BESA) program (version 2.0, 1995) was used to calculate dipole sources. The latency period for the activation of five distinct cortical zones, including the prefrontal and/or the frontal lobe, the ipsilateral temporoparietal cortex, the anterior portion of the supplementary motor area (SMA) and the contralateral parietal

  16. The myocardial protective effect of dexmedetomidine in high-risk patients undergoing aortic vascular surgery

    PubMed Central

    Soliman, Rabie; Zohry, Gomaa

    2016-01-01

    Objective: The aim of the study was to assess the effect of dexmedetomidine in high-risk patients undergoing aortic vascular surgery. Design: A randomized prospective study. Setting: Cairo University, Egypt. Materials and Methods: The study included 150 patients undergoing aortic vascular surgery. Intervention: The patients were classified into two groups (n = 75). Group D: The patients received a loading dose of 1 μg/kg dexmedetomidine over 15 min before induction and maintained as an infusion of 0.3 μg/kg/h to the end of the procedure. Group C: The patients received an equal volume of normal saline. The medication was prepared by the nursing staff and given to anesthetist blindly. Measurements: The monitors included the heart rate, mean arterial blood pressure, central venous pressure, electrocardiogram (ECG), serum troponin I level, end-tidal sevoflurane, and total dose of morphine in addition transthoracic echocardiography to the postoperative in cases with elevated serum troponin I level. Main Results: The dexmedetomidine decreased heart rate and minimized the changes in blood pressure compared to control group (P < 0.05). Furthermore, it decreased the incidence of myocardial ischemia reflected by troponin I level, ECG changes, and the development of new regional wall motion abnormalities (P < 0.05). Dexmedetomidine decreased the requirement for nitroglycerin and norepinephrine compared to control group (P < 0.05). The incidence of hypotension and bradycardia was significantly higher with dexmedetomidine (P < 0.05). Conclusion: The dexmedetomidine is safe and effective in patients undergoing aortic vascular surgery. It decreases the changes in heart rate and blood pressure during the procedures. It provides cardiac protection in high-risk patients reflected by decreasing the incidence of myocardial ischemia and serum level of troponin. The main side effects of dexmedetomidine were hypotension and bradycardia. PMID:27716690

  17. Dysfunction of calcium/calmodulin/CaM kinase IIα cascades in the medial prefrontal cortex in post-traumatic stress disorder.

    PubMed

    Wen, Yu; Li, Bin; Han, Fang; Wang, Enhua; Shi, Yuxiu

    2012-11-01

    Post-traumatic stress disorder (PTSD) is a significant problem that may affect individuals who have been exposed to a traumatic event or events, including combat, violent crime or childhood abuse. The medial prefrontal cortex (mPFC) is known to be significantly involved in emotional adjustment, particularly introspection, amygdala inhibition and emotional memory. In the acute phase of severe traumatic stress, the mPFC appears to undergo a change in plasticity for a short time, which suggests that the mPFC may be the reponse-sensitizing region. Calcium (Ca2+) is one of most significant intracellular messengers; the appropriate concentration of Ca2+ is necessary for neuronal excitability. When the Ca2+ concentration increases, Ca2+, calmodulin (CaM) and CaM kinase IIα (CaMKIIα) combine together to form the Ca2+‑CaM‑CaMKIIα signaling pathway, which is important in the plasticity of the central nervous system, learning and memory, mind, behavior and other types of cognitive activities. Our team studied the changes in the Ca2+-CaM-CaMKIIα levels in the mPFC of rats following a single-prolonged stress (SPS). The SPS, a credible method for establishing a rat model of PTSD, has been internationally recognized. The free intracellular Ca2+ concentration in the mPFC in the PTSD group was significantly higher than that in the control group 1 day after SPS exposure (P<0.05) and decreased 7 days after SPS; CaM expression significantly increased, while CaMKIIα expression significantly decreased in the mPFC 1 day after SPS compared with the control group. These findings suggest dysfunction of the Ca2+-CaM-CaMKIIα cascades in the mPFC, which may relate to the pathogenesis of the abnormal functioning of the mPFC in PTSD.

  18. Neuronal activity in somatosensory cortex related to tactile exploration.

    PubMed

    Fortier-Poisson, Pascal; Smith, Allan M

    2016-01-01

    The very light contact forces (∼0.60 N) applied by the fingertips during tactile exploration reveal a clearly optimized sensorimotor strategy. To investigate the cortical mechanisms involved with this behavior, we recorded 230 neurons in the somatosensory cortex (S1), as two monkeys scanned different surfaces with the fingertips in search of a tactile target without visual feedback. During the exploration, the monkeys, like humans, carefully controlled the finger forces. High-friction surfaces offering greater tangential shear force resistance to the skin were associated with decreased normal contact forces. The activity of one group of neurons was modulated with either the normal or tangential force, with little or no influence from the orthogonal force component. A second group responded to kinetic friction or the ratio of tangential to normal forces rather than responding to a specific parameter, such as force magnitude or direction. A third group of S1 neurons appeared to respond to particular vectors of normal and tangential force on the skin. Although 45 neurons correlated with scanning speed, 32 were also modulated by finger forces, suggesting that forces on the finger should be considered as the primary parameter encoding the skin compliance and that finger speed is a secondary parameter that co-varies with finger forces. Neurons (102) were also tested with different textures, and the activity of 62 of these increased or decreased in relation to the surface friction.

  19. Neuronal activity in somatosensory cortex related to tactile exploration

    PubMed Central

    Fortier-Poisson, Pascal

    2015-01-01

    The very light contact forces (∼0.60 N) applied by the fingertips during tactile exploration reveal a clearly optimized sensorimotor strategy. To investigate the cortical mechanisms involved with this behavior, we recorded 230 neurons in the somatosensory cortex (S1), as two monkeys scanned different surfaces with the fingertips in search of a tactile target without visual feedback. During the exploration, the monkeys, like humans, carefully controlled the finger forces. High-friction surfaces offering greater tangential shear force resistance to the skin were associated with decreased normal contact forces. The activity of one group of neurons was modulated with either the normal or tangential force, with little or no influence from the orthogonal force component. A second group responded to kinetic friction or the ratio of tangential to normal forces rather than responding to a specific parameter, such as force magnitude or direction. A third group of S1 neurons appeared to respond to particular vectors of normal and tangential force on the skin. Although 45 neurons correlated with scanning speed, 32 were also modulated by finger forces, suggesting that forces on the finger should be considered as the primary parameter encoding the skin compliance and that finger speed is a secondary parameter that co-varies with finger forces. Neurons (102) were also tested with different textures, and the activity of 62 of these increased or decreased in relation to the surface friction. PMID:26467519

  20. Apoptotic microtubules delimit an active caspase free area in the cellular cortex during the execution phase of apoptosis

    PubMed Central

    Oropesa-Ávila, M; Fernández-Vega, A; de la Mata, M; Maraver, J G; Cordero, M D; Cotán, D; de Miguel, M; Calero, C P; Paz, M V; Pavón, A D; Sánchez, M A; Zaderenko, A P; Ybot-González, P; Sánchez-Alcázar, J A

    2013-01-01

    Apoptotic microtubule network (AMN) is organized during apoptosis, forming a cortical structure beneath plasma membrane, which has an important role in preserving cell morphology and plasma membrane permeability. The aim of this study was to examine the role of AMN in maintaining plasma membrane integrity during the execution phase of apoptosis. We demonstrated in camptothecin-induced apoptosis in H460 cells that AMN delimits an active caspase free area beneath plasma membrane that permits the preservation of cellular cortex and transmembrane proteins. AMN depolymerization in apoptotic cells by a short exposure to colchicine allowed active caspases to reach the cellular cortex and cleave many key proteins involved in plasma membrane structural support, cell adhesion and ionic homeostasis. Cleavage of cellular cortex and plasma membrane proteins, such as α-spectrin, paxilin, focal adhesion kinase (FAK), E-cadherin and integrin subunit β4 was associated with cell collapse and cell detachment. Otherwise, cleavage-mediated inactivation of calcium ATPase pump (PMCA-4) and Na+/Ca2+ exchanger (NCX) involved in cell calcium extrusion resulted in calcium overload. Furthermore, cleavage of Na+/K+ pump subunit β was associated with altered sodium homeostasis. Cleavage of cell cortex and plasma membrane proteins in apoptotic cells after AMN depolymerization increased plasma permeability, ionic imbalance and bioenergetic collapse, leading apoptotic cells to secondary necrosis. The essential role of caspase-mediated cleavage in this process was demonstrated because the concomitant addition of colchicine that induces AMN depolymerization and the pan-caspase inhibitor z-VAD avoided the cleavage of cortical and plasma membrane proteins and prevented apoptotic cells to undergo secondary necrosis. Furthermore, the presence of AMN was also critical for proper phosphatidylserine externalization and apoptotic cell clearance by macrophages. These results indicate that AMN is essential

  1. Void and pore formation inside the hair cortex by a denaturation and super-contraction process occurring during hair setting with hot irons.

    PubMed

    Gamez-Garcia, Manuel

    2011-01-01

    An analysis of hair fibers from donors that frequently use hot irons for hair straightening showed the presence of multiple pores and voids (φ approximately 0.1-1.5 μm) that extend from the cuticle sheath to regions inside the hair cortex. Pore formation in the cortex was found to be confined at its periphery and could be reproduced in the laboratory with virgin hair fibers after the application of various hot-iron straightening cycles. The appearance of pores and voids in the cortex was found to be associated to the production of hot water vapor while the fiber is undergoing mechanical elongation or contraction. The number of pores was seen to rapidly increase with temperature in the range from 190 to 220°C and also with the number of straightening cycles. Larger hair voids (φ approximately 2-5 μm) were also detected in the cortex. The small pores found at the cortex periphery appear to occur by the simultaneous occurrence of rearrangement of hair proteins, fiber mechanical contraction/expansion, and the flow of super-heated steam. Hot irons create, thus, the conditions for the onset of pore formation as the high temperatures produce superheated steam and soften the native state of hair proteins by a process involving denaturation and changes in the crystalline regions.

  2. [Features of the structure of the adrenal cortex in domesticated Vulpes fulvus silver foxes during postnatal ontogeny].

    PubMed

    Lutsenko, N D; Trut, L N; Ivanova, L N

    1980-01-01

    Studies have been made on the structure of the adrenal cortex in relatively wild and domesticated male and female silver foxes at the age of 1-7 days, 1, 2 and 8 months. It was demonstrated that during domestication, deep morphological changes in the adrenal cortex take place which indicate the decrease of functional activity in the fascicular zone and the increase of the activity in the reticular zone. Differences found in the first days of postnatal life become more evident in further ontogenesis.

  3. Secular period decreasing of detached chromospherically active binaries

    NASA Astrophysics Data System (ADS)

    Luo, Chang Qing; Zhang, Xiao Bin; Deng, Li Cai; Luo, Yang Ping; Luo, Zhi Quan; Yang, Shu Zheng

    2010-05-01

    The long-term orbital period changes of a large sample of detached chromospherically active binaries (CABs) were studied. Eleven such systems were found to be undergoing secular period decreases with the rates of -6.3×10-9 to -1.1×10-6 days per year. The period decreasing rates are found to vary depending on the orbital period. The longer the orbital period is, the more rapidly the period decreases. Following Stepien (Mon. Not. R. Astron. Soc. 274:1019, 1995), the period decreasing rate predicted by angular momentum loss (AML) caused by magnetic wind is computed for each system. A comparison between the observed and calculated period decreasing rates shows that the former values are obviously larger than the latter by 1-3 orders of magnitude. It suggests that the magnetic wind is not likely the determinant mechanism driving the AML in these systems. Finally, the orbital angular momentum (AM) and the rate of AML, dot{J} , are computed for each system. It shows that the AM have a similar change with the orbital period like d P/d t does, but logdot{J}/J presents no strict changing with the kinematical ages.

  4. Factors Affecting Patients Undergoing Cosmetic Surgery in Bushehr, Southern Iran

    PubMed Central

    Salehahmadi, Zeinab; Rafie, Seyyed Reza

    2012-01-01

    BACKGROUND Although, there have been extensive research on the motivations driving patient to undergo cosmetic procedures, there is still a big question mark on the persuasive factors which may lead individuals to undergo cosmetic surgery. The present study evaluated various factors affecting patients undergoing cosmetic surgery in Bushehr, Southern Iran. METHODS From 24th March 2011 to 24th March 2012, eighty-one women and 20 men who wished to be operated in Fatemeh Zahra Hospital in Bushehr, Southern Iran and Pars Clinic, Iran were enrolled by a simple random sampling method. They all completed a questionnaire to consider reasons for cosmetic procedures. The collected data were statistically analyzed. RESULTS Demographical, sociological and psychological factors such as age, gender, educational level, marital status, media, perceived risks, output quality, depression and self-improvement were determined as factors affecting tendency of individuals to undergo cosmetic surgery in this region. Trend to undergo cosmetic surgery was more prevalent in educational below bachelor degree, married subjects, women population of 30-45 years age group. Education level, age, marital status and gender were respectively the influential factors in deciding to undergo cosmetic surgery. Among the socio-psychological factors, self-improvement, finding a better job opportunity, rivalry, media, health status as well as depression were the most persuasive factors to encourage people to undergo cosmetic surgery too. Cost risk was not important for our samples in decision making to undergo cosmetic surgery. CONCLUSION We need to fully understand the way in which the combination of demographic, social and psychological factors influence decision-making to undergo cosmetic surgery. PMID:25734051

  5. Homeostatic modulation of stimulation-dependent plasticity in human motor cortex.

    PubMed

    Ilić, N V; Milanović, S; Krstić, J; Bajec, D D; Grajić, M; Ilić, T V

    2011-01-01

    Since recently, it is possible, using noninvasive cortical stimulation, such as the protocol of paired associative stimulation (PAS), to induce the plastic changes in the motor cortex, in humans that mimic Hebb's model of learning. Application of TMS conjugated with peripheral electrical stimulation at strictly coherent temporal manner lead to convergence of inputs in the sensory-motor cortex, with the consequent synaptic potentiation or weakening, if applied repetitively. However, when optimal interstimulus interval (ISI) for induction of LTP-like effects is applied as a single pair, Motor evoked potential (MEP) amplitude inhibition is observed, the paradigm known as short-latency afferent inhibition (SLAI). Aiming to resolve this paradox, PAS protocols were applied, with 200 repetitions of TMS pulses paired with median nerve electrical stimulation, at ISI equal to individual latencies of evoked response of somatosensory cortex (N(20)) (PAS(LTP)), and at ISI of N(20) shortened for 5 msec (PAS(LTD)) - protocols that mimic LTP-like changes in the human motor cortex. MEP amplitudes before, during and after interventions were measured as an indicator based on output signals originating from the motor system. Post-intervention MEP amplitudes following the TMS protocols of PAS(LTP) and PAS(LTD) were facilitated and depressed, respectively, contrary to MEP amplitudes during intervention. During PAS(LTP) MEP amplitudes were significantly decreased in case of PAS(LTP), while in the case of PAS(LTD) an upward trend was observed. In conclusions, a possible explanation for the seemingly paradoxical effect of PAS can be found in the mechanism of homeostatic modulation of plasticity. Those findings indicate the existence of complex relationships in the development of plasticity induced by stimulation, depending on the level of the previous motor cortex excitability.

  6. Cocaine cue–induced dopamine release in the human prefrontal cortex

    PubMed Central

    Milella, Michele S.; Fotros, Aryandokht; Gravel, Paul; Casey, Kevin F.; Larcher, Kevin; Verhaeghe, Jeroen A.J.; Cox, Sylvia M.L.; Reader, Andrew J.; Dagher, Alain; Benkelfat, Chawki; Leyton, Marco

    2016-01-01

    Background Accumulating evidence indicates that drug-related cues can induce dopamine (DA) release in the striatum of substance abusers. Whether these same cues provoke DA release in the human prefrontal cortex remains unknown. Methods We used high-resolution positron emission tomography with [18F]fallypride to measure cortical and striatal DA D2/3 receptor availability in the presence versus absence of drug-related cues in volunteers with current cocaine dependence. Results Twelve individuals participated in our study. Among participants reporting a craving response (9 of 12), exposure to the cocaine cues significantly decreased [18F]fallypride binding potential (BPND) values in the medial orbitofrontal cortex and striatum. In all 12 participants, individual differences in the magnitude of craving correlated with BPND changes in the medial orbitofrontal cortex, dorsolateral prefrontal cortex, anterior cingulate, and striatum. Consistent with the presence of autoreceptors on mesostriatal but not mesocortical DA cell bodies, midbrain BPND values were significantly correlated with changes in BPND within the striatum but not the cortex. The lower the midbrain D2 receptor levels, the greater the striatal change in BPND and self-reported craving. Limitations Limitations of this study include its modest sample size, with only 2 female participants. Newer tracers might have greater sensitivity to cortical DA release. Conclusion In people with cocaine use disorders, the presentation of drug-related cues induces DA release within cortical and striatal regions. Both effects are associated with craving, but only the latter is regulated by midbrain autoreceptors. Together, the results suggest that cortical and subcortical DA responses might both influence drug-focused incentive motivational states, but with separate regulatory mechanisms. PMID:26900792

  7. Modulation of proprioceptive integration in the motor cortex shapes human motor learning.

    PubMed

    Rosenkranz, Karin; Rothwell, John C

    2012-06-27

    Sensory and motor systems interact closely during movement performance. Furthermore, proprioceptive feedback from ongoing movements provides an important input for successful learning of a new motor skill. Here, we show in humans that attention to proprioceptive input during a purely sensory task can influence subsequent learning of a novel motor task. We applied low-amplitude vibration to the abductor pollicis brevis (APB) muscle of eight healthy volunteers for 15 min while they discriminated either a small change in vibration frequency or the presence of a simultaneous weak cutaneous stimulus. Before and after the sensory attention tasks, we evaluated the following in separate experiments: (1) sensorimotor interaction in the motor cortex by testing the efficacy of proprioceptive input to reduce GABA(A)ergic intracortical inhibition using paired-pulse transcranial magnetic stimulation, and (2) how well the same subjects learned a ballistic thumb abduction task using the APB muscle. Performance of the vibration discrimination task increased the interaction of proprioceptive input with motor cortex excitability in the APB muscle, whereas performance in the cutaneous discrimination task had the opposite effect. There was a significant correlation between the integration of proprioceptive input in the motor cortex and the motor learning gain: increasing the integration of proprioceptive input from the APB increased the rate of motor learning and reduced performance variability, while decreasing proprioceptive integration had opposite effects. These findings suggest that the sensory attention tasks transiently change how proprioceptive input is integrated into the motor cortex and that these sensory changes drive subsequent learning behavior in the human motor cortex.

  8. Altered somatosensory barrel cortex refinement in the developing brain of Mecp2-null mice.

    PubMed

    Moroto, M; Nishimura, A; Morimoto, M; Isoda, K; Morita, T; Yoshida, M; Morioka, S; Tozawa, T; Hasegawa, T; Chiyonobu, T; Yoshimoto, K; Hosoi, H

    2013-11-06

    Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the methyl-CpG binding protein 2 (MeCP2) gene. In previous studies, monoaminergic dysfunctions have been detected in patients with RTT and in a murine model of RTT, the Mecp2-null mouse. Therefore, the pathogenesis of RTT is thought to involve impairments in the monoaminergic systems. However, there have been limited data showing that the impairment of monoamines leads to early symptoms during development. We used histochemistry to study the somatosensory barrel cortex in the B6.129P2(C)-Mecp2(tm1.1Bird) mouse model of RTT. The barrel cortex is widely used to investigate neuronal development and its regulation by various neurotransmitters including 5-HT. 5-HT levels were measured by high performance liquid chromatography with electrochemical detection (HPLC/EC), and serotonin transporter (SERT) and 5-HT1B receptor mRNAs were measured in the somatosensory cortex, thalamus and striatum on postnatal days (P) 10, P20 and P40. Mecp2-null mice (Mecp2-/y) had significantly smaller barrel fields than age-matched wild-type controls (Mecp2+/y) on P10 and P40, but the topographic map was accurately formed. Levels of 5-HT, and SERT and 5-HT1B receptor mRNA expression in the somatosensory cortex did not differ significantly between the Mecp2-null and wild-type mice on P10. However, thalamic 5-HT was reduced in Mecp2-null mice. Our data indicate that a lack of MeCP2 may disturb the refinement of the barrel cortex in the early postnatal period. Our findings suggest that a decrease in thalamic 5-HT might be involved in this phenomenon.

  9. Brain and heart sodium channel subtype mRNA expression in rat cerebral cortex.

    PubMed Central

    Yarowsky, P J; Krueger, B K; Olson, C E; Clevinger, E C; Koos, R D

    1991-01-01

    The expression of mRNAs coding for the alpha subunit of rat brain and rat heart sodium channels has been studied in adult and neonatal rat cerebral cortex using the reverse transcription-polymerase chain reaction (RT-PCR). Rat brain sodium channel subtype I, II, IIA, and III sequences were simultaneously amplified in the same PCR using a single oligonucleotide primer pair matched to all four subtype sequences. Identification of each subtype-specific product was inferred from the appearance of unique fragments when the product was digested with specific restriction enzymes. By using this RT-PCR method, products arising from mRNAs for all four brain sodium channel subtypes were identified in RNA extracted from adult rat cerebral cortex. The predominant component was type IIA with lesser levels of types I, II, and III. In contrast, the type II and IIA sequences were the predominant RT-PCR products in neonatal rat cortex, with slightly lower levels of type III and undetectable levels of type I. Thus, from neonate to adult, type II mRNA levels decrease relative to type IIA levels. Using a similar approach, we detected mRNA coding for the rat heart sodium channel in neonatal and adult rat cerebral cortex and in adult rat heart. These results reveal that mRNAs coding for the heart sodium channel and all four previously sequenced rat brain sodium channel subtypes are expressed in cerebral cortex and that type II and IIA channels may be differentially regulated during development. Images PMID:1658783

  10. Altered SPECT 123I-iomazenil Binding in the Cingulate Cortex of Children with Anorexia Nervosa

    PubMed Central

    Nagamitsu, Shinichiro; Sakurai, Rieko; Matsuoka, Michiko; Chiba, Hiromi; Ozono, Shuichi; Tanigawa, Hitoshi; Yamashita, Yushiro; Kaida, Hayato; Ishibashi, Masatoshi; Kakuma, Tatsuki; Croarkin, Paul E.; Matsuishi, Toyojiro

    2016-01-01

    Several lines of evidence suggest that anxiety plays a key role in the development and maintenance of anorexia nervosa (AN) in children. The purpose of this study was to examine cortical GABA(A)-benzodiazepine receptor binding before and after treatment in children beginning intensive AN treatment. Brain single-photon emission computed tomography (SPECT) measurements using 123I-iomazenil, which binds to GABA(A)-benzodiazepine receptors, was performed in 26 participants with AN who were enrolled in a multimodal treatment program. Sixteen of the 26 participants underwent a repeat SPECT scan immediately before discharge at conclusion of the intensive treatment program. Eating behavior and mood disturbances were assessed using Eating Attitudes Test with 26 items (EAT-26) and the short form of the Profile of Mood States (POMS). Clinical outcome scores were evaluated after a 1-year period. We examined association between relative iomazenil-binding activity in cortical regions of interest and psychometric profiles and determined which psychometric profiles show interaction effects with brain regions. Further, we determined if binding activity could predict clinical outcome and treatment changes. Higher EAT-26 scores were significantly associated with lower iomazenil-binding activity in the anterior and posterior cingulate cortex. Higher POMS subscale scores were significantly associated with lower iomazenil-binding activity in the left frontal, parietal cortex, and posterior cingulate cortex (PCC). “Depression–Dejection” and “Confusion” POMS subscale scores, and total POMS score showed interaction effects with brain regions in iomazenil-binding activity. Decreased binding in the anterior cingulate cortex and left parietal cortex was associated with poor clinical outcomes. Relative binding increases throughout the PCC and occipital gyrus were observed after weight gain in children with AN. These findings suggest that cortical GABAergic receptor binding is altered

  11. The roles of superficial amygdala and auditory cortex in music-evoked fear and joy.

    PubMed

    Koelsch, Stefan; Skouras, Stavros; Fritz, Thomas; Herrera, Perfecto; Bonhage, Corinna; Küssner, Mats B; Jacobs, Arthur M

    2013-11-01

    This study investigates neural correlates of music-evoked fear and joy with fMRI. Studies on neural correlates of music-evoked fear are scant, and there are only a few studies on neural correlates of joy in general. Eighteen individuals listened to excerpts of fear-evoking, joy-evoking, as well as neutral music and rated their own emotional state in terms of valence, arousal, fear, and joy. Results show that BOLD signal intensity increased during joy, and decreased during fear (compared to the neutral condition) in bilateral auditory cortex (AC) and bilateral superficial amygdala (SF). In the right primary somatosensory cortex (area 3b) BOLD signals increased during exposure to fear-evoking music. While emotion-specific activity in AC increased with increasing duration of each trial, SF responded phasically in the beginning of the stimulus, and then SF activity declined. Psychophysiological Interaction (PPI) analysis revealed extensive emotion-specific functional connectivity of AC with insula, cingulate cortex, as well as with visual, and parietal attentional structures. These findings show that the auditory cortex functions as a central hub of an affective-attentional network that is more extensive than previously believed. PPI analyses also showed functional connectivity of SF with AC during the joy condition, taken to reflect that SF is sensitive to social signals with positive valence. During fear music, SF showed functional connectivity with visual cortex and area 7 of the superior parietal lobule, taken to reflect increased visual alertness and an involuntary shift of attention during the perception of auditory signals of danger.

  12. Cerebral cortex hyperthyroidism of newborn mct8-deficient mice transiently suppressed by lat2 inactivation.

    PubMed

    Núñez, Bárbara; Martínez de Mena, Raquel; Obregon, Maria Jesus; Font-Llitjós, Mariona; Nunes, Virginia; Palacín, Manuel; Dumitrescu, Alexandra M; Morte, Beatriz; Bernal, Juan

    2014-01-01

    Thyroid hormone entry into cells is facilitated by transmembrane transporters. Mutations of the specific thyroid hormone transporter, MCT8 (Monocarboxylate Transporter 8, SLC16A2) cause an X-linked syndrome of profound neurological impairment and altered thyroid function known as the Allan-Herndon-Dudley syndrome. MCT8 deficiency presumably results in failure of thyroid hormone to reach the neural target cells in adequate amounts to sustain normal brain development. However during the perinatal period the absence of Mct8 in mice induces a state of cerebral cortex hyperthyroidism, indicating increased brain access and/or retention of thyroid hormone. The contribution of other transporters to thyroid hormone metabolism and action, especially in the context of MCT8 deficiency is not clear. We have analyzed the role of the heterodimeric aminoacid transporter Lat2 (Slc7a8), in the presence or absence of Mct8, on thyroid hormone concentrations and on expression of thyroid hormone-dependent cerebral cortex genes. To this end we generated Lat2-/-, and Mct8-/yLat2-/- mice, to compare with wild type and Mct8-/y mice during postnatal development. As described previously the single Mct8 KO neonates had a transient increase of 3,5,3'-triiodothyronine concentration and expression of thyroid hormone target genes in the cerebral cortex. Strikingly the absence of Lat2 in the double Mct8Lat2 KO prevented the effect of Mct8 inactivation in newborns. The Lat2 effect was not observed from postnatal day 5 onwards. On postnatal day 21 the Mct8 KO displayed the typical pattern of thyroid hormone concentrations in plasma, decreased cortex 3,5,3'-triiodothyronine concentration and Hr expression, and concomitant Lat2 inactivation produced little to no modifications. As Lat2 is expressed in neurons and in the choroid plexus, the results support a role for Lat2 in the supply of thyroid hormone to the cerebral cortex during early postnatal development.

  13. Usefulness of Acoustic Monitoring of Respiratory Rate in Patients Undergoing Endoscopic Submucosal Dissection.

    PubMed

    Suzuki, Takayoshi; Tsuda, Shingo; Nakae, Hirohiko; Imai, Jin; Sawamoto, Kana; Kijima, Maiko; Tsukune, Yoko; Uchida, Tetsufumi; Igarashi, Muneki; Koike, Jun; Matsushima, Masashi; Suzuki, Toshiyasu; Mine, Tetsuya

    2016-01-01

    Aim. The study assessed the usefulness of a recently developed method for respiratory rate (RR) monitoring in patients undergoing endoscopic submucosal dissection (ESD) under deep sedation. Methods. Study subjects comprised 182 consecutive patients with esophageal cancer or gastric cancer undergoing ESD. The usefulness of acoustic RR monitoring was assessed by retrospectively reviewing the patients' records for age, gender, height, weight, past history, serum creatinine, RR before ESD, and total dose of sedative. Results. Respiratory suppression was present in 37.9% of (69/182) patients. Continuous monitoring of RR led to detection of respiratory suppression in all these patients. RR alone was decreased in 24 patients, whereas both RR and blood oxygen saturation were decreased in 45 patients. Univariate analysis showed female gender, height, weight, and RR before treatment to be significantly associated with respiratory suppression. Multivariate analysis showed RR before treatment to be the only significant independent predictor [odds ratio (OR) 0.83, 95% confidence interval (CI) 0.73-0.95, and P = 0.006] of respiratory suppression. Conclusion. In this study, the difference in RR before treatment between patients with and without respiratory suppression was subtle. Therefore, we suggest that acoustic RR monitoring should be considered in patients undergoing ESD under sedation to prevent serious respiratory complications.

  14. Usefulness of Acoustic Monitoring of Respiratory Rate in Patients Undergoing Endoscopic Submucosal Dissection

    PubMed Central

    Tsuda, Shingo; Nakae, Hirohiko; Imai, Jin; Sawamoto, Kana; Kijima, Maiko; Tsukune, Yoko; Uchida, Tetsufumi; Igarashi, Muneki; Koike, Jun; Matsushima, Masashi; Suzuki, Toshiyasu; Mine, Tetsuya

    2016-01-01

    Aim. The study assessed the usefulness of a recently developed method for respiratory rate (RR) monitoring in patients undergoing endoscopic submucosal dissection (ESD) under deep sedation. Methods. Study subjects comprised 182 consecutive patients with esophageal cancer or gastric cancer undergoing ESD. The usefulness of acoustic RR monitoring was assessed by retrospectively reviewing the patients' records for age, gender, height, weight, past history, serum creatinine, RR before ESD, and total dose of sedative. Results. Respiratory suppression was present in 37.9% of (69/182) patients. Continuous monitoring of RR led to detection of respiratory suppression in all these patients. RR alone was decreased in 24 patients, whereas both RR and blood oxygen saturation were decreased in 45 patients. Univariate analysis showed female gender, height, weight, and RR before treatment to be significantly associated with respiratory suppression. Multivariate analysis showed RR before treatment to be the only significant independent predictor [odds ratio (OR) 0.83, 95% confidence interval (CI) 0.73–0.95, and P = 0.006] of respiratory suppression. Conclusion. In this study, the difference in RR before treatment between patients with and without respiratory suppression was subtle. Therefore, we suggest that acoustic RR monitoring should be considered in patients undergoing ESD under sedation to prevent serious respiratory complications. PMID:26858748

  15. The Effect of Therapeutic Touch on Pain and Fatigue of Cancer Patients Undergoing Chemotherapy

    PubMed Central

    Aghabati, Nahid; Pour Esmaiel, Zahra

    2010-01-01

    Despite major advances in pain management, cancer pain is managed poorly in 80% of the patients with cancer. Due to deleterious side effects of pharmacology therapy in these people, there is an urgent need for clinical trials of non-pharmacological interventions. To examine the effect of therapeutic touch (TT) on the pain and fatigue of the cancer patients undergoing chemotherapy, a randomized and three-groups experimental study—experimental (TT), placebo (placebo TT), and control (usual care)—was carried out. Ninety patients undergoing chemotherapy, exhibiting pain and fatigue of cancer, were randomized into one of the three groups in the Cancer Center of Imam Khomeini Hospital in Tehran, Iran. Pain and fatigue were measured and recorded by participants before and after the intervention for 5 days (once a day). The intervention consisted of 30 min TT given once a day for 5 days between 10:00 a.m. and 10:30 a.m. The Visual Analogue Scale (VAS) of pain and the Rhoten Fatigue Scale (RFS) were completed for 5 days before and after the intervention by the subjects. The TT (significant) was more effective in decreasing pain and fatigue of the cancer patients undergoing chemotherapy than the usual care group, while the placebo group indicated a decreasing trend in pain and fatigue scores compared with the usual care group. PMID:18955319

  16. The necessity of rostrolateral prefrontal cortex for higher-level sequential behavior

    PubMed Central

    Desrochers, Theresa M.; Chatham, Christopher H.; Badre, David

    2015-01-01

    Summary Frontal neocortex is thought to support our highest intellectual abilities, including our ability to plan and enact a sequence of tasks toward a desired goal. In everyday life, such task sequences are abstract in that they do not require consistent movement sequences and are often assembled “on the fly”. Yet, remarkably little is known about the necessity of frontal sub-regions for such control. Participants repeatedly completed sequences of simple tasks during fMRI scanning. Rostrolateral prefrontal cortex (RLPFC) activation ramped over sequence position, and reset at the initiation of each new sequence. To establish the necessity and function of RLPFC in this task, participants performed the sequential task while undergoing transcranial magnetic stimulation (TMS) of the RLPFC versus two prefrontal control regions. Across two independent experiments, only RLPFC stimulation increasingly disrupted task performance as each sequence progressed. These data establish RLPFC as necessary for uncertainty resolution during sequence-level control. PMID:26402612

  17. Developmental stability of taurine's activation on glycine receptors in cultured neurons of rat auditory cortex.

    PubMed

    Tang, Zheng-Quan; Lu, Yun-Gang; Chen, Lin

    2008-01-03

    Taurine is an endogenous amino acid that can activate glycine and/or gamma-aminobutyric acid type A (GABA(A)) receptors in the central nervous system. During natural development, taurine's receptor target undergoes a shift from glycine receptors to GABA(A) receptors in cortical neurons. Here, we demonstrate that taurine's receptor target in cortical neurons remains stable during in vitro development. With whole-cell patch-clamp recordings, we found that taurine always activated glycine receptors, rather than GABA(A) receptors, in neurons of rat auditory cortex cultured for 5-22 days. Our results suggest that the functional sensitivity of glycine and GABA(A) receptors to taurine is critically regulated by their developmental environments.

  18. Gateways of ventral and dorsal streams in mouse visual cortex

    PubMed Central

    Wang, Quanxin; Gao, Enquan; Burkhalter, Andreas

    2011-01-01

    It is widely held that the spatial processing functions underlying rodent navigation are similar to those encoding human episodic memory (Doeller et al, 2010). Spatial and nonspatial information are provided by all senses including vision. It has been suggested that visual inputs are fed to the navigational network in cortex and hippocampus through dorsal and ventral intracortical streams (Whitlock et al, 2008), but this has not been shown directly in rodents. We have used cyto- and chemoarchitectonic markers, topographic mapping of receptive fields and pathway tracing to determine in mouse visual cortex whether the lateromedial (LM) and the anterolateral fields (AL), which are the principal targets of primary visual cortex (V1) (Wang and Burkhalter, 2007) specialized for processing nonspatial and spatial visual information (Gao et al, 2006), are distinct areas with diverse connections. We have found that the LM/AL border coincides with a change in type 2 muscarinic acetylcholine receptor (m2AChR) expression in layer 4 and with the representation of the lower visual field periphery. Our quantitative analyses further show that LM strongly projects to temporal cortex as well as the lateral entorhinal cortex, which has weak spatial selectivity (Hargreaves et al, 2005). In contrast, AL has stronger connections with posterior parietal cortex, motor cortex and the spatially selective medial entorhinal cortex (Haftig et al, 2005). These results support the notion that LM and AL are architecturally, topographically and connectionally distinct areas of extrastriate visual cortex and that they are gateways for ventral and dorsal streams. PMID:21289200

  19. Neurons and circuits for odor processing in the piriform cortex.

    PubMed

    Bekkers, John M; Suzuki, Norimitsu

    2013-07-01

    Increased understanding of the early stages of olfaction has lead to a renewed interest in the higher brain regions responsible for forming unified 'odor images' from the chemical components detected by the nose. The piriform cortex, which is one of the first cortical destinations of olfactory information in mammals, is a primitive paleocortex that is critical for the synthetic perception of odors. Here we review recent work that examines the cellular neurophysiology of the piriform cortex. Exciting new findings have revealed how the neurons and circuits of the piriform cortex process odor information, demonstrating that, despite its superficial simplicity, the piriform cortex is a remarkably subtle and intricate neural circuit.

  20. Differential activation of human core, non-core and auditory-related cortex during speech categorization tasks as revealed by intracranial recordings

    PubMed Central

    Steinschneider, Mitchell; Nourski, Kirill V.; Rhone, Ariane E.; Kawasaki, Hiroto; Oya, Hiroyuki; Howard, Matthew A.

    2014-01-01

    Speech perception requires that sounds be transformed into speech-related objects with lexical and semantic meaning. It is unclear at what level in the auditory pathways this transformation emerges. Primary auditory cortex has been implicated in both representation of acoustic sound attributes and sound objects. While non-primary auditory cortex located on the posterolateral superior temporal gyrus (PLST) is clearly involved in acoustic-to-phonetic pre-lexical representations, it is unclear what role this region plays in auditory object formation. Additional data support the importance of prefrontal cortex in the formation of auditory objects, while other data would implicate this region in auditory object selection. To help clarify the respective roles of auditory and auditory-related cortex in the formation and selection of auditory objects, we examined high gamma activity simultaneously recorded directly from Heschl's gyrus (HG), PLST and prefrontal cortex, while subjects performed auditory semantic detection tasks. Subjects were patients undergoing evaluation for treatment of medically intractable epilepsy. We found that activity in posteromedial HG and early activity on PLST was robust to sound stimuli regardless of their context, and minimally modulated by tasks. Later activity on PLST could be strongly modulated by semantic context, but not by behavioral performance. Activity within prefrontal cortex also was related to semantic context, and did co-vary with behavior. We propose that activity in posteromedial HG and early activity on PLST primarily reflect the representation of spectrotemporal sound attributes. Later activity on PLST represents a pre-lexical processing stage and is an intermediate step in the formation of word objects. Activity in prefrontal cortex appears directly involved in word object selection. The roles of other auditory and auditory-related cortical areas in the formation of word objects remain to be explored. PMID:25157216

  1. Effect of early isolation on signal transfer in the entorhinal cortex-dentate-hippocampal system.

    PubMed

    Bartesaghi, R; Raffi, M; Ciani, E

    2006-02-01

    Deprivation of socio-sensory interactions during early life impairs brain function in adulthood. In previous investigations we showed that early isolation severely affects neuron development in several structures of the hippocampal region, including the entorhinal cortex. In the present study we investigated the effects of early isolation on signal processing along the entorhinal cortex-dentate-CA3-CA1 system, a major memory circuit of the hippocampal region. Male and female guinea-pigs were assigned at 6-7 days of age to either a social or an isolated environment. At 90-100 days of age the animals were anesthetized and field potentials were recorded from the entorhinal cortex-dentate-CA3-CA1 circuit, driven by dorsal psalterium commissural volleys. Analysis of the input-output function in the different structures showed that in isolated males there was a small reduction in the input-output function of the population excitatory postsynaptic potential and population spike evoked in layer II of the entorhinal cortex. No changes occurred in isolated females. In isolated males and females there was a reduction in the input-output function of the population excitatory postsynaptic potential and population spike evoked in the dentate gyrus, CA3 and CA1, but this effect was larger in males. In isolated males, but not in females, the population spike/population excitatory postsynaptic potential ratio was reduced in all investigated structures, indicating that in males the size of the discharged neuron population was reduced more than due to the decreased input. Results show that isolation reduces the synaptic function in the whole entorhinal cortex-dentate gyrus-CA3-CA1 system. While the entorhinal cortex was moderately impaired, the dentate-hippocampal system was more severely affected. The impairment in the signal transfer along the entorhinal cortex-dentate gyrus-CA3-CA1 system was heavier in males, confirming the larger susceptibility of this sex to early experience

  2. Motor cortex stimulation in Parkinson's disease.

    PubMed

    De Rose, Marisa; Guzzi, Giusy; Bosco, Domenico; Romano, Mary; Lavano, Serena Marianna; Plastino, Massimiliano; Volpentesta, Giorgio; Marotta, Rosa; Lavano, Angelo

    2012-01-01

    Motor Cortex Stimulation (MCS) is less efficacious than Deep Brain Stimulation (DBS) in Parkinson's disease. However, it might be proposed to patients excluded from DBS or unresponsive to DBS. Ten patients with advanced PD underwent unilateral MCS contralaterally to the worst clinical side. A plate electrode was positioned over the motor cortex in the epidural space through single burr hole after identification of the area with neuronavigation and neurophysiological tests. Clinical assessment was performed by total UPDRS, UPDRS III total, UPDRS III-items 27-31, UPDRS IV, and UPDRS II before implantation in off-medication and on-medication states and after surgery at 1, 3, 6, 12, 18, 24, and 36 months in on-medication/on-stimulation and off-medication/on-stimulation states. We assessed changes of quality of life, throughout the Parkinson's disease quality of life scale (PDQoL-39), and the dose of anti-Parkinson's disease medications, throughout the Ldopa equivalent daily dose (LEDD). During off-medication state, we observed moderate and transitory reduction of total UPDRS and UPDRS total scores and significant and long-lasting improvement in UPDRS III items 27-31 score for axial symptoms. There was marked reduction of UPDRS IV score and LEDD. PDQL-39 improvement was also significant. No important complications and adverse events occurred.

  3. Representation of numerosity in posterior parietal cortex

    PubMed Central

    Roitman, Jamie D.; Brannon, Elizabeth M.; Platt, Michael L.

    2012-01-01

    Humans and animals appear to share a similar representation of number as an analog magnitude on an internal, subjective scale. Neurological and neurophysiological data suggest that posterior parietal cortex (PPC) is a critical component of the circuits that form the basis of numerical abilities in humans. Patients with parietal lesions are impaired in their ability to access the deep meaning of numbers. Acalculiac patients with inferior parietal damage often have difficulty performing arithmetic (2 + 4?) or number bisection (what is between 3 and 5?) tasks, but are able to recite multiplication tables and read or write numerals. Functional imaging studies of neurologically intact humans performing subtraction, number comparison, and non-verbal magnitude comparison tasks show activity in areas within the intraparietal sulcus (IPS). Taken together, clinical cases and imaging studies support a critical role for parietal cortex in the mental manipulation of numerical quantities. Further, responses of single PPC neurons in non-human primates are sensitive to the numerosity of visual stimuli independent of low-level stimulus qualities. When monkeys are trained to make explicit judgments about the numerical value of such stimuli, PPC neurons encode their cardinal numerical value; without such training PPC neurons appear to encode numerical magnitude in an analog fashion. Here we suggest that the spatial and integrative properties of PPC neurons contribute to their critical role in numerical cognition. PMID:22666194

  4. Divergent Plasticity of Prefrontal Cortex Networks

    PubMed Central

    Moghaddam, Bita; Homayoun, Houman

    2010-01-01

    The ‘executive’ regions of the prefrontal cortex (PFC) such as the dorsolateral PFC (dlPFC) and its rodent equivalent medial PFC (mPFC) are thought to respond in concert with the ‘limbic’ regions of the PFC such as the orbitofrontal (OFC) cortex to orchestrate behavior that is consistent with context and expected outcome. Both groups of regions have been implicated in behavioral abnormalities associated with addiction and psychiatric disorders, in particular, schizophrenia and mood disorders. Theories about the pathophysiology of these disorders, however, incorporate abnormalities in discrete PFC regions independently of each other or assume they are one and the same and, thus, bunch them under umbrella of ‘PFC dysfunction.’ Emerging data from animal studies suggest that mPFC and OFC neurons display opposing patterns of plasticity during associative learning and in response to repeated exposure to psychostimulants. These data corroborate clinical studies reporting different patterns of activation in OFC versus dlPFC in individuals with schizophrenia or addictive disorders. These suggest that concomitant but divergent engagement of discrete PFC regions is critical for learning stimulus-outcome associations, and the execution of goal-directed behavior that is based on these associations. An atypical interplay between these regions may lead to abnormally high or low salience assigned to stimuli, resulting in symptoms that are fundamental to many psychiatric and addictive disorders, including attentional deficits, improper affective response to stimuli, and inflexible or impulsive behavior. PMID:17912252

  5. Faces and objects in macaque cerebral cortex.

    PubMed

    Tsao, Doris Y; Freiwald, Winrich A; Knutsen, Tamara A; Mandeville, Joseph B; Tootell, Roger B H

    2003-09-01

    How are different object categories organized by the visual system? Current evidence indicates that monkeys and humans process object categories in fundamentally different ways. Functional magnetic resonance imaging (fMRI) studies suggest that humans have a ventral temporal face area, but such evidence is lacking in macaques. Instead, face-responsive neurons in macaques seem to be scattered throughout temporal cortex, with some relative concentration in the superior temporal sulcus (STS). Here, using fMRI in alert fixating macaque monkeys and humans, we found that macaques do have discrete face-selective patches, similar in relative size and number to face patches in humans. The face patches were embedded within a large swath of object-selective cortex extending from V4 to rostral TE. This large region responded better to pictures of intact objects compared to scrambled objects, with different object categories eliciting different patterns of activity, as in the human. Overall, our results suggest that humans and macaques share a similar brain architecture for visual object processing.

  6. Frequency Specific Modulation of Human Somatosensory Cortex

    PubMed Central

    Feurra, Matteo; Paulus, Walter; Walsh, Vincent; Kanai, Ryota

    2011-01-01

    Oscillatory neuronal activities are commonly observed in response to sensory stimulation. However, their functional roles are still the subject of debate. One-way to probe the roles of oscillatory neural activities is to deliver alternating current to the cortex at biologically relevant frequencies and examine whether such stimulation influences perception and cognition. In this study, we tested whether transcranial alternating current stimulation (tACS) over the primary somatosensory cortex (SI) could elicit tactile sensations in humans in a frequency-dependent manner. We tested the effectiveness of tACS over SI at frequency bands ranging from 2 to 70 Hz. Our results show that stimulation in alpha (10–14 Hz) and high gamma (52–70 Hz) frequency range produces a tactile sensation in the contralateral hand. A weaker effect was also observed for beta (16–20 Hz) stimulation. These findings highlight the frequency dependency of effective tACS over SI with the effective frequencies corresponding to those observed in previous electroencephalography/magnetoencephalography studies of tactile perception. Our present study suggests that tACS could be used as a powerful online stimulation technique to reveal the causal roles of oscillatory brain activities. PMID:21713181

  7. Ocular integration in the human visual cortex.

    PubMed

    Horton, Jonathan C

    2006-10-01

    Human striate cortex contains an orderly map of the contralateral visual field, which is distorted to make a disproportionate amount of tissue available for the representation of the macula. Engrafted on the retinotopic map is a system of alternating inputs known as ocular dominance columns. These columns consist of interleaved bands of geniculocortical afferents in layer 4C serving either the right eye or the left eye. They can be revealed in humans with a history of prior visual loss in one eye by processing striate cortex for cytochrome oxidase at autopsy. Because their geniculate input is segregated, cells within ocular dominance columns in layer 4C respond to stimulation of one eye only. These monocular cells converge onto binocular cells in other layers, integrating signals from the two eyes. The columns in humans appear similar to those found in many primate species, including the macaque. In the squirrel monkey, however, the occurrence of ocular dominance columns is highly variable. Some squirrel monkeys lack columns, yet they seem to have no impairment of visual function. In animals with weakly expressed columns, one can detect a cortical pattern of metabolic activity corresponding to retinal blood vessels. It appears because visual deprivation from shadows cast by blood vessels induces remodeling of geniculocortical afferents, in a manner akin to the shrinkage of ocular dominance columns from congenital cataract. Although the function of ocular dominance columns is unknown, their metabolism is altered in strabismus, suggesting a role in visual suppression.

  8. Dynamic cortex stripping for vertebra evaluation

    NASA Astrophysics Data System (ADS)

    Stieger, James; Burns, Joseph E.; Yao, Jianhua; Summers, Ronald M.

    2015-03-01

    Vertebral cortex removal through cancellous bone reconstruction (CBR) algorithms on CT has been shown to enhance the detection rate of bone metastases by radiologists and reduce average reading time per case. Removal of the cortical bone provides an unobstructed view of the inside of vertebrae without any anomalous distractions. However, these algorithms rely on the assumption that the cortical bone of vertebrae can be removed without the identification of the endosteal cortical margin. We present a method for the identification of the endosteal cortical margin based on vertebral models and CT intensity information. First, triangular mesh models are created using the marching cubes algorithm. A search region is established along the normal of the surface and the image gradient is calculated at every point along the search region. The location with the greatest image gradient is selected as the corresponding point on the endosteal cortical margin. In order to analyze the strength of this method, ground truth and control models were also created. Our method was shown to have a significantly reduce the average error from 0.80 mm +/- 0.14 mm to 0.65 mm +/- 0.17 mm (p <0.0001) when compared to erosion. This method can potentially improve CBR algorithms, which improve visualization of cancellous bone lesions such as metastases, by more accurately identifying the inner wall of the vertebral cortex.

  9. Motor Cortex Stimulation in Parkinson's Disease

    PubMed Central

    De Rose, Marisa; Guzzi, Giusy; Bosco, Domenico; Romano, Mary; Lavano, Serena Marianna; Plastino, Massimiliano; Volpentesta, Giorgio; Marotta, Rosa; Lavano, Angelo

    2012-01-01

    Motor Cortex Stimulation (MCS) is less efficacious than Deep Brain Stimulation (DBS) in Parkinson's disease. However, it might be proposed to patients excluded from DBS or unresponsive to DBS. Ten patients with advanced PD underwent unilateral MCS contralaterally to the worst clinical side. A plate electrode was positioned over the motor cortex in the epidural space through single burr hole after identification of the area with neuronavigation and neurophysiological tests. Clinical assessment was performed by total UPDRS, UPDRS III total, UPDRS III-items 27–31, UPDRS IV, and UPDRS II before implantation in off-medication and on-medication states and after surgery at 1, 3, 6, 12, 18, 24, and 36 months in on-medication/on-stimulation and off-medication/on-stimulation states. We assessed changes of quality of life, throughout the Parkinson's disease quality of life scale (PDQoL-39), and the dose of anti-Parkinson's disease medications, throughout the Ldopa equivalent daily dose (LEDD). During off-medication state, we observed moderate and transitory reduction of total UPDRS and UPDRS total scores and significant and long-lasting improvement in UPDRS III items 27–31 score for axial symptoms. There was marked reduction of UPDRS IV score and LEDD. PDQL-39 improvement was also significant. No important complications and adverse events occurred. PMID:23213520

  10. Plasticity between neuronal pairs in layer 4 of visual cortex varies with synapse state

    PubMed Central

    Sáez, Ignacio; Friedlander, Michael J.

    2010-01-01

    In neocortex, the induction and expression of long-term potentiation (LTP) and depression (LTD) vary depending on cortical area and laminae of pre- and postsynaptic neurons. Layer 4 (L4) is the initial site of sensory afference in barrel cortex and primary visual cortex (V1) where excitatory inputs from thalamus, layer 6 (L6) and neighboring L4 cells are integrated. However, little is known about plasticity within L4. We studied plasticity at excitatory synaptic connections between pairs and triplets of interconnected L4 neurons in guinea pig V1 using a fixed delay pairing protocol. Plasticity outcomes were heterogeneous, with some connections undergoing LTP (n=7/42), some LTD (n=19/42) and some not changing (NC, n=16/42). While quantal analysis revealed both pre- and postsynaptic plasticity expression components, reduction in quantal size (a postsynaptic property) contributing to LTD was ubiquitous whereas in some cell pairs this change was over-ridden by an increase in the probability of neurotransmitter release (a presynaptic property) resulting in LTP. These changes depended on the initial reliability of the connections: highly reliable connections depressed with contributions from pre- and postsynaptic effects; unreliable connections potentiated due to the predominance of presynaptic enhancement. Interestingly, very strong, reliable pairs of connected cells showed little plasticity. Pairs of connected cells with a common pre- or postsynaptic L4 cell behaved independently, undergoing plasticity of different or opposite signs. Release probability of a connection with initial 100% failure rate was enhanced after pairing, potentially avoiding silencing of the presynaptic terminal and maintaining L4-L4 synapses in a broader dynamic range. PMID:19955381

  11. Prefrontal Cortex Networks Shift from External to Internal Modes during Learning

    PubMed Central

    Brincat, Scott L.

    2016-01-01

    As we learn about items in our environment, their neural representations become increasingly enriched with our acquired knowledge. But there is little understanding of how network dynamics and neural processing related to external information changes as it becomes laden with “internal” memories. We sampled spiking and local field potential activity simultaneously from multiple sites in the lateral prefrontal cortex (PFC) and the hippocampus (HPC)—regions critical for sensory associations—of monkeys performing an object paired-associate learning task. We found that in the PFC, evoked potentials to, and neural information about, external sensory stimulation decreased while induced beta-band (∼11–27 Hz) oscillatory power and synchrony associated with “top-down” or internal processing increased. By contrast, the HPC showed little evidence of learning-related changes in either spiking activity or network dynamics. The results suggest that during associative learning, PFC networks shift their resources from external to internal processing. SIGNIFICANCE STATEMENT As we learn about items in our environment, their representations in our brain become increasingly enriched with our acquired “top-down” knowledge. We found that in the prefrontal cortex, but not the hippocampus, processing of external sensory inputs decreased while internal network dynamics related to top-down processing increased. The results suggest that during learning, prefrontal cortex networks shift their resources from external (sensory) to internal (memory) processing. PMID:27629722

  12. Organization of myelin in the mouse somatosensory barrel cortex and the effects of sensory deprivation.

    PubMed

    Barrera, Kyrstle; Chu, Philip; Abramowitz, Jason; Steger, Robert; Ramos, Raddy L; Brumberg, Joshua C

    2013-04-01

    In rodents, the barrel cortex is a specialized area within the somatosensory cortex that processes signals from the mystacial whiskers. We investigated the normal development of myelination in the barrel cortex of mice, as well as the effects of sensory deprivation on this pattern. Deprivation was achieved by trimming the whiskers on one side of the face every other day from birth. In control mice, myelin was not present until postnatal day 14 and did not show prominence until postnatal day 30; adult levels of myelination were reached by the end of the second postnatal month. Unbiased stereology was used to estimate axon density in the interbarrel septal region and barrel walls as well as the barrel centers. Myelin was significantly more concentrated in the interbarrel septa/barrel walls than in the barrel centers in both control and sensory-deprived conditions. Sensory deprivation did not impact the onset of myelination but resulted in a significant decrease in myelinated axons in the barrel region and decreased the amount of myelin ensheathing each axon. Visualization of the oligodendrocyte nuclear marker Olig2 revealed a similar pattern of myelin as seen using histochemistry, but with no significant changes in Olig2+ nuclei following sensory deprivation. Consistent with the anatomical results showing less myelination, local field potentials revealed slower rise times following trimming. Our results suggest that myelination develops relatively late and can be influenced by sensory experience.

  13. Modeling the time course of attention signals in human primary visual cortex

    NASA Astrophysics Data System (ADS)

    Silver, Michael A.

    2006-02-01

    Previous neuroimaging studies have documented the existence of attention signals in human visual cortex, but little is known about the time course of these signals. A recent study reported persistent activity in early visual cortex whose duration was correlated with the duration of sustained attention1. The present study extends these findings by modeling the time course of sustained attention signals with a linear function with duration equal to the period of sustained attention but with variable amplitude and slope. Subjects performed a visual detection task in which a variable-duration delay period occurred before every target presentation. This design required the subjects to allocate visuospatial attention throughout the delay period. Functional magnetic resonance imaging (fMRI) was used to record activity in primary visual cortex (cortical area V1) during performance of the task. There were significant individual differences in the time course of attention signals, with some subjects displaying time courses consistent with constant amplitude attention signals, while others showed decreasing amplitude of attention-related activity during the delay period. These individual differences in time course of attention signals were correlated with behavioral response bias, suggesting that they may reflect differences in the types of attention used by the subjects to perform the detection task. In particular, those subjects who had constant amplitude sustained attention signals may have been employing relatively more endogenous, or top-down attention, while the subjects who exhibited attention signals that decreased over time may have been using relatively more exogenous, or bottom-up attention.

  14. Pairing tone trains with vagus nerve stimulation induces temporal plasticity in auditory cortex.

    PubMed

    Shetake, Jai A; Engineer, Navzer D; Vrana, Will A; Wolf, Jordan T; Kilgard, Michael P

    2012-01-01

    The selectivity of neurons in sensory cortex can be modified by pairing neuromodulator release with sensory stimulation. Repeated pairing of electrical stimulation of the cholinergic nucleus basalis, for example, induces input specific plasticity in primary auditory cortex (A1). Pairing nucleus basalis stimulation (NBS) with a tone increases the number of A1 neurons that respond to the paired tone frequency. Pairing NBS with fast or slow tone trains can respectively increase or decrease the ability of A1 neurons to respond to rapidly presented tones. Pairing vagus nerve stimulation (VNS) with a single tone alters spectral tuning in the same way as NBS-tone pairing without the need for brain surgery. In this study, we tested whether pairing VNS with tone trains can change the temporal response properties of A1 neurons. In naïve rats, A1 neurons respond strongly to tones repeated at rates up to 10 pulses per second (pps). Repeatedly pairing VNS with 15 pps tone trains increased the temporal following capacity of A1 neurons and repeatedly pairing VNS with 5 pps tone trains decreased the temporal following capacity of A1 neurons. Pairing VNS with tone trains did not alter the frequency selectivity or tonotopic organization of auditory cortex neurons. Since VNS is well tolerated by patients, VNS-tone train pairing represents a viable method to direct temporal plasticity in a variety of human conditions associated with temporal processing deficits.

  15. Anesthetic effects of isoflurane on the tonotopic map and neuronal population activity in the rat auditory cortex.

    PubMed

    Noda, Takahiro; Takahashi, Hirokazu

    2015-09-01

    Since its discovery nearly four decades ago, sequential microelectrode mapping using hundreds of recording sites has been able to reveal a precise tonotopic organization of the auditory cortex. Despite concerns regarding the effects that anesthesia might have on neuronal responses to tones, anesthesia was essential for these experiments because such dense mapping was elaborate and time-consuming. Here, taking an 'all-at-once' approach, we investigated how isoflurane modifies spatiotemporal activities by using a dense microelectrode array. The array covered the entire auditory cortex in rats, including the core and belt cortices. By comparing neuronal activity in the awake state with activity under isoflurane anesthesia, we made four observations. First, isoflurane anesthesia did not modify the tonotopic topography within the auditory cortex. Second, in terms of general response properties, isoflurane anesthesia decreased the number of active single units and increased their response onset latency. Third, in terms of tuning properties, isoflurane anesthesia shifted the response threshold without changing the shape of the frequency response area and decreased the response quality. Fourth, in terms of population activities, isoflurane anesthesia increased the noise correlations in discharges and phase synchrony in local field potential (LFP) oscillations, suggesting that the anesthesia made neuronal activities redundant at both single-unit and LFP levels. Thus, while isoflurane anesthesia had little effect on the tonotopic topography, its profound effects on neuronal activities decreased the encoding capacity of the auditory cortex.

  16. Anticoagulation in patients with atrial fibrillation undergoing coronary stent implantation.

    PubMed

    Bernard, A; Fauchier, L; Pellegrin, C; Clementy, N; Saint Etienne, C; Banerjee, A; Naudin, D; Angoulvant, D

    2013-09-01

    In patients with atrial fibrillation (AF) undergoing coronary stent implantation, the optimal antithrombotic strategy is unclear. We evaluated whether use of oral anticoagulation (OAC) was associated with any benefit in morbidity or mortality in patients with AF, high risk of thromboembolism (TE) (CHA2DS2-VASC score ≥ 2) and coronary stent implantation. Among 8,962 unselected patients with AF seen between 2000 and 2010, a total of 2,709 (30%) had coronary artery disease and 417/2,709 (15%) underwent stent implantation while having CHA2DS2-VASC score ≥ 2. During follow-up (median=650 days), all TE, bleeding episodes, and major adverse cardiac events (i.e. death, acute myocardial infarction, target lesion revascularisation) were recorded. At discharge, 97/417 patients (23%) received OAC, which was more likely to be prescribed in patients with permanent AF and in those treated for elective stent implantation. The incidence of outcome event rates was not significantly different in patients treated and those not treated with OAC. However, in multivariate analysis, the lack of OAC at discharge was independently associated with increased risk of death/stroke/systemic TE (relative risk [RR] =2.18, 95% confidence interval [CI] 1.02-4.67, p=0.04), with older age (RR =1.12, 1.04-1.20, p=0.003), heart failure (RR =3.26, 1.18-9.01, p=0.02), and history of stroke (RR =18.87, 3.11-111.11, p=0.001). In conclusion, in patients with AF and high thromboembolic risk after stent implantation, use of OAC was independently associated with decreased risk of subsequent death/stroke/systemic TE, suggesting that OAC should be systematically used in this patient population.

  17. Responsive measures to prehabilitation in patients undergoing bowel resection surgery.

    PubMed

    Kim, Do Jun; Mayo, Nancy E; Carli, Franco; Montgomery, David L; Zavorsky, Gerald S

    2009-02-01

    Surgical patients often show physiological and metabolic distress, muscle weakness, and long hospital stays. Physical conditioning might help recovery. We attempted to identify the most responsive measure of aerobic fitness from a four-week pre-surgical aerobic exercise program (prehabilitation) in patients undergoing major bowel resection. Twenty-one subjects randomized two to one (exercise: control) scheduled for colorectal surgery. Fourteen subjects [Body Mass Index (BMI) = 27 +/- 6 kg/m(2); maximal oxygen uptake (VO(2max)) = 22 +/- 10 ml/kg/min] underwent 3.8 +/- 1.2 weeks (27 +/- 8 sessions) of progressive, structured pre-surgical aerobic exercise training at 40 to 65% of heart rate reserve (%HRR). Peak power output was the only maximal measure that was responsive to training [26 +/- 27%, Effects Size (ES) = 0.24; Standardized Response Mean (SRM) = 1.05; p < 0.05]. For the submaximal measures, heart rate and oxygen uptake during submaximal exercise was most responsive to training (decrease by 13% +/- 15%, ES = -0.24; SRM = -0.57; and 7% +/- 6%, ES = -0.40; SRM -0.97; p < 0.05) at an exercise intensity of 76 +/- 47 W. There was no change to maximal or submaximal measures in the control group. The distance walked over six minutes improved in both groups (by approximately 30 m), but the effect size and t-statistic were higher in the exercise group. Heart rate and oxygen uptake during submaximal exercise, and peak power output are the most responsive measures to four weeks of prehabilitation in subjects with low initial fitness.

  18. Metabolic Changes in the Bilateral Visual Cortex of the Monocular Blind Macaque: A Multi-Voxel Proton Magnetic Resonance Spectroscopy Study.

    PubMed

    Wu, Lingjie; Tang, Zuohua; Feng, Xiaoyuan; Sun, Xinghuai; Qian, Wen; Wang, Jie; Jin, Lixin; Jiang, Jingxuan; Zhong, Yufeng

    2017-02-01

    The metabolic changes accompanied with adaptive plasticity in the visual cortex after early monocular visual loss were unclear. In this study, we detected the metabolic changes in bilateral visual cortex of normal (group A) and monocular blind macaque (group B) for studying the adaptive plasticity using multi-voxel proton magnetic resonance spectroscopy ((1)H-MRS) at 32 months after right optic nerve transection. Then, we compared the N-Acetyl aspartate (NAA)/Creatine (Cr), myoinositol (Ins)/Cr, choline (Cho)/Cr and Glx (Glutamate + glutamine)/Cr ratios in the visual cortex between two groups, as well as between the left and right visual cortex of group A and B. Compared with group A, in the bilateral visual cortex, a decreased NAA/Cr and Glx/Cr ratios in group B were found, which was more clearly in the right visual cortex; whereas the Ins/Cr and Cho/Cr ratios of group B were increased. All of these findings were further confirmed by immunohistochemical staining. In conclusion, the difference of metabolic ratios can be detected by multi-voxel (1)H-MRS in the visual cortex between groups A and B, which was valuable for investigating the adaptive plasticity of monocular blind macaque.

  19. Re-emergence of hand-muscle representations in human motor cortex after hand allograft

    PubMed Central

    Vargas, Claudia D.; Aballéa, Antoine; Rodrigues, Érika C.; Reilly, Karen T.; Mercier, Catherine; Petruzzo, Palmina; Dubernard, Jean M.; Sirigu, Angela

    2009-01-01

    The human primary motor cortex (M1) undergoes considerable reorganization in response to traumatic upper limb amputation. The representations of the preserved arm muscles expand, invading portions of M1 previously dedicated to the hand, suggesting that former hand neurons are reassigned to the control of remaining proximal upper limb muscles. Hand allograft offers a unique opportunity to study the reversibility of such long-term cortical changes. We used transcranial magnetic stimulation in patient LB, who underwent bilateral hand transplantation 3 years after a traumatic amputation, to longitudinally track both the emergence of intrinsic (from the donor) hand muscles in M1 as well as changes in the representation of stump (upper arm and forearm) muscles. The same muscles were also mapped in patient CD, the first bilateral hand allograft recipient. Newly transplanted intrinsic muscles acquired a cortical representation in LB's M1 at 10 months postgraft for the left hand and at 26 months for the right hand. The appearance of a cortical representation of transplanted hand muscles in M1 coincided with the shrinkage of stump muscle representations for the left but not for the right side. In patient CD, transcranial magnetic stimulation performed at 51 months postgraft revealed a complete set of intrinsic hand-muscle representations for the left but not the right hand. Our findings show that newly transplanted muscles can be recognized and integrated into the patient's motor cortex. PMID:19366678

  20. Transformation of spatiotemporal dynamics in the macaque vestibular system from otolith afferents to cortex

    PubMed Central

    Laurens, Jean; Liu, Sheng; Yu, Xiong-Jie; Chan, Raymond; Dickman, David; DeAngelis, Gregory C; Angelaki, Dora E

    2017-01-01

    Sensory signals undergo substantial recoding when neural activity is relayed from sensors through pre-thalamic and thalamic nuclei to cortex. To explore how temporal dynamics and directional tuning are sculpted in hierarchical vestibular circuits, we compared responses of macaque otolith afferents with neurons in the vestibular and cerebellar nuclei, as well as five cortical areas, to identical three-dimensional translational motion. We demonstrate a remarkable spatio-temporal transformation: otolith afferents carry spatially aligned cosine-tuned translational acceleration and jerk signals. In contrast, brainstem and cerebellar neurons exhibit non-linear, mixed selectivity for translational velocity, acceleration, jerk and position. Furthermore, these components often show dissimilar spatial tuning. Moderate further transformation of translation signals occurs in the cortex, such that similar spatio-temporal properties are found in multiple cortical areas. These results suggest that the first synapse represents a key processing element in vestibular pathways, robustly shaping how self-motion is represented in central vestibular circuits and cortical areas. DOI: http://dx.doi.org/10.7554/eLife.20787.001 PMID:28075326

  1. Task-relevant modulation of primary somatosensory cortex suggests a prefrontal-cortical sensory gating system.

    PubMed

    Schaefer, Michael; Heinze, Hans-Jochen; Rotte, Michael

    2005-08-01

    Increasing evidence suggests that somatosensory information is modulated cortically for task-specific sensory inflow: Several studies report short-term adaptation of representational maps in primary somatosensory cortex (SI) due to attention or induced by task-related motor activity such as handwriting. Recently, it has been hypothesized that the frontal or prefrontal cortex may modulate SI. In order to test this hypothesis, we studied the functional organization of SI while subjects performed the Tower of Hanoi task. This task is known to be related to activation of frontal or prefrontal areas. The functional organization of SI while performing the Tower of Hanoi task was compared to the organization of SI during performing the same movements but without the Tower of Hanoi task and with rest. Topography of SI was assessed using neuromagnetic source imaging based on tactile stimulation of the first (D1) and fifth digits (D5). Performing the Tower of Hanoi task was accompanied by plastic changes in SI as indicated by significant shifts in the cortical representations of D1 and D5: They moved further apart during the Tower of Hanoi task compared to the control task containing the same movements but without the cognitive characteristic. Thus, we conclude that SI maps undergo dynamic modulation depending on motor tasks with different cognitive demands. The results suggest that this short-term plasticity may be regulated by a prefrontal-cortical sensory gating system.

  2. Face sensorimotor cortex and its neuroplasticity related to orofacial sensorimotor functions.

    PubMed

    Avivi-Arber, Limor; Martin, Ruth; Lee, Jye-Chang; Sessle, Barry J

    2011-12-01

    This review describes evidence in subprimates and primates that the face primary somatosensory cortex (face SI) and primary motor cortex (face MI) are involved in sensorimotor integration and control of orofacial motor functions that include semiautomatic movements (e.g., chewing, swallowing) and voluntary movements (e.g., jaw-opening). The review also notes that the neuroplastic capabilities of the face SI and face MI have recently been documented, and may reflect or allow for functional adaptation (or maladaptation) of the orofacial sensorimotor system to an altered oral state or oral motor behaviour. They may contribute to the processes whereby patients undergoing oral rehabilitation can (or cannot) restore the lost orofacial sensorimotor functions. Such understanding is important since pain, injuries to the oral tissues, and alterations to the dental occlusion induced by tooth loss or attrition are common occurrences in humans that may sometimes be accompanied by impaired oral sensorimotor functions. Furthermore, impaired oral sensorimotor functions are common in many neurological disorders, sometimes making the most vital functions of eating, swallowing and speaking difficult and thereby reducing the patient's quality of life. It has also been well documented that such negative consequences can be improved following oral rehabilitation as patients adapt, for example, to a new dental prosthesis aimed at restoring function. Therefore, understanding the mechanisms and cortical neuroplastic processes underlying orofacial sensorimotor functions and adaptation is also important for the development of new therapeutic strategies to facilitate recovery of patients suffering from orofacial pain and sensorimotor disorders and improve their quality of life.

  3. Determination of axonal and dendritic orientation distributions within the developing cerebral cortex by diffusion tensor imaging.

    PubMed

    Jespersen, Sune Nørhøj; Leigland, Lindsey A; Cornea, Anda; Kroenke, Christopher D

    2012-01-01

    As neurons of the developing brain form functional circuits, they undergo morphological differentiation. In immature cerebral cortex, radially-oriented cellular processes of undifferentiated neurons impede water diffusion parallel, but not perpendicular, to the pial surface, as measured via diffusion-weighted magnetic resonance imaging, and give rise to water diffusion anisotropy. As the cerebral cortex matures, the loss of water diffusion anisotropy accompanies cellular morphological differentiation. A quantitative relationship is proposed here to relate water diffusion anisotropy measurements directly to characteristics of neuronal morphology. This expression incorporates the effects of local diffusion anisotropy within cellular processes, as well as the effects of anisotropy in the orientations of cellular processes. To obtain experimental support for the proposed relationship, tissue from 13 and 31 day-old ferrets was stained using the rapid Golgi technique, and the 3-D orientation distribution of neuronal processes was characterized using confocal microscopic examination of reflected visible light images. Coregistration of the MRI and Golgi data enables a quantitative evaluation of the proposed theory, and excellent agreement with the theoretical results, as well as agreement with previously published values for locally-induced water diffusion anisotropy and volume fraction of the neuropil, is observed.

  4. Crosstalk between intracellular and extracellular signals regulating interneuron production, migration and integration into the cortex

    PubMed Central

    Peyre, Elise; Silva, Carla G.; Nguyen, Laurent

    2015-01-01

    During embryogenesis, cortical interneurons are generated by ventral progenitors located in the ganglionic eminences of the telencephalon. They travel along multiple tangential paths to populate the cortical wall. As they reach this structure they undergo intracortical dispersion to settle in their final destination. At the cellular level, migrating interneurons are highly polarized cells that extend and retract processes using dynamic remodeling of microtubule and actin cytoskeleton. Different levels of molecular regulation contribute to interneuron migration. These include: (1) Extrinsic guidance cues distributed along migratory streams that are sensed and integrated by migrating interneurons; (2) Intrinsic genetic programs driven by specific transcription factors that grant specification and set the timing of migration for different subtypes of interneurons; (3) Adhesion molecules and cytoskeletal elements/regulators that transduce molecular signalings into coherent movement. These levels of molecular regulation must be properly integrated by interneurons to allow their migration in the cortex. The aim of this review is to summarize our current knowledge of the interplay between microenvironmental signals and cell autonomous programs that drive cortical interneuron porduction, tangential migration, and intergration in the developing cerebral cortex. PMID:25926769

  5. Cold or Calculating? Reduced Activity in the Subgenual Cingulate Cortex Reflects Decreased Emotional Aversion to Harming in Counterintuitive Utilitarian Judgment

    ERIC Educational Resources Information Center

    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…

  6. Plasma corticosterone responses to lesions and stimulations of the limbic thalami nuclei, medial mammillary nucleus and cingulate cortex.

    PubMed

    Suárez, M; Perassi, N I

    1988-06-01

    The influence of extrahypothalamic limbic structures on adrenocortical activity was investigated in female adult rats. Bilateral lesions on the anteromedial thalami nucleus (AMTN), anteroventral thalami nucleus (AVTN) or the posterior cingulate cortex (PCC) all elicited a significant decrease on plasma corticosterone, while their electrochemical stimulation produced a significant increase with respect to animals with sham lesions or sham stimulation. In contrast, after lesions of the dorsomedial thalami nucleus (DMTN), medial mammillary nucleus (pars lateralis) (MMN) or retrosplenial cortex (RC), values of plasma corticosterone were significantly higher than those found in controls, whereas following their stimulation plasma corticosterone levels were lower than in controls. Bilateral lesions or stimulations of anterior cingulate cortex had no significant effect upon corticosterone secretion. These findings may be interpreted as indicative of the existence of excitatory (AMTN, AVTN, and PCC) and inhibitory (DMTN, MMN and RC) central nervous structures for the control of corticoadrenal secretion besides those already known.

  7. Toward unraveling reading–related modulations of tDCS–induced neuroplasticity in the human visual cortex

    PubMed Central

    Antal, Andrea; Ambrus, Géza Gergely; Chaieb, Leila

    2014-01-01

    Stimulation using weak electrical direct currents has shown to be capable of inducing polarity-dependent diminutions or elevations in motor and visual cortical excitability. The aim of the present study was to test if reading during transcranial direct current stimulation (tDCS) is able to modify stimulation-induced plasticity in the visual cortex. Phosphene thresholds (PTs) in 12 healthy subjects were recorded before and after 10 min of anodal, cathodal, and sham tDCS in combination with reading. Reading alone decreased PTs significantly, compared to the sham tDCS condition without reading. Interestingly, after both anodal and cathodal stimulation there was a tendency toward smaller PTs. Our results support the observation that tDCS-induced plasticity is highly dependent on the cognitive state of the subject during stimulation, not only in the case of motor cortex but also in the case of visual cortex stimulation. PMID:24999339

  8. Brain measures of nociception using near-infrared spectroscopy in patients undergoing routine screening colonoscopy.

    PubMed

    Becerra, Lino; Aasted, Christopher M; Boas, David A; George, Edward; Yücel, Meryem A; Kussman, Barry D; Kelsey, Peter; Borsook, David

    2016-04-01

    Colonoscopy is an invaluable tool for the screening and diagnosis of many colonic diseases. For most colonoscopies, moderate sedation is used during the procedure. However, insufflation of the colon produces a nociceptive stimulus that is usually accompanied by facial grimacing/groaning while under sedation. The objective of this study was to evaluate whether a nociceptive signal elicited by colonic insufflation could be measured from the brain. Seventeen otherwise healthy patients (age 54.8 ± 9.1; 6 female) undergoing routine colonoscopy (ie, no history of significant medical conditions) were monitored using near-infrared spectroscopy (NIRS). Moderate sedation was produced using standard clinical protocols for midazolam and meperidine, titrated to effect. Near-infrared spectroscopy data captured during the procedure was analyzed offline to evaluate the brains' responses to nociceptive stimuli evoked by the insufflation events (defined by physician or observing patients' facial responses). Analysis of NIRS data revealed a specific, reproducible prefrontal cortex activity corresponding to times when patients grimaced. The pattern of the activation is similar to that previously observed during nociceptive stimuli in awake healthy individuals, suggesting that this approach may be used to evaluate brain activity evoked by nociceptive stimuli under sedation, when there is incomplete analgesia. Although some patients report recollection of procedural pain after the procedure, the effects of repeated nociceptive stimuli in surgical patients may contribute to postoperative changes including chronic pain. The results from this study indicate that NIRS may be a suitable technology for continuous nociceptive afferent monitoring in patients undergoing sedation and could have applications under sedation or anesthesia.

  9. The retrosplenial cortex and object recency memory in the rat.

    PubMed

    Powell, Anna L; Vann, Seralynne D; Olarte-Sánchez, Cristian M; Kinnavane, Lisa; Davies, Moira; Amin, Eman; Aggleton, John P; Nelson, Andrew J D

    2017-04-10

    It has been proposed that the retrosplenial cortex forms part of a "where/when" information network. The present study focussed on the related issue of whether retrosplenial cortex also contributes to "what/when" information, by examining object recency memory. In Experiment 1, rats with retrosplenial lesions were found to be impaired at distinguishing the temporal order of objects presented in a continuous series ('Within-Block' condition). The same lesioned rats could, however, distinguish between objects that had been previously presented in one of two discrete blocks ('Between-Block' condition). Experiment 2 used intact rats to map the expression of the immediate-early gene c-fos in retrosplenial cortex following performance of a between-block, recency discrimination. Recency performance correlated positively with levels of c-fos expression in both granular and dysgranular retrosplenial cortex (areas 29 and 30). Expression of c-fos in the granular retrosplenial cortex also correlated with prelimbic cortex and ventral subiculum c-fos activity, the latter also correlating with recency memory performance. The combined findings from both experiments reveal an involvement of the retrosplenial cortex in temporal order memory, which includes both between-block and within-block problems. The current findings also suggest that the rat retrosplenial cortex comprises one of a group of closely interlinked regions that enable recency memory, including the hippocampal formation, medial diencephalon, and medial frontal cortex. In view of the well-established importance of the retrosplenial cortex for spatial learning, the findings support the notion that, with its frontal and hippocampal connections, retrosplenial cortex has a key role for both what/when and where/when information. This article is protected by copyright. All rights reserved.

  10. 76 FR 18553 - Agency Forms Undergoing Paperwork Reduction Act Review

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  15. Subthalamic nucleus stimulation modulates motor cortex oscillatory activity in Parkinson's disease.

    PubMed

    Devos, D; Labyt, E; Derambure, P; Bourriez, J L; Cassim, F; Reyns, N; Blond, S; Guieu, J D; Destée, A; Defebvre, L

    2004-02-01

    In Parkinson's disease, impaired motor preparation has been related to an increased latency in the appearance of movement-related desynchronization (MRD) throughout the contralateral primary sensorimotor (PSM) cortex. Internal globus pallidus (GPi) stimulation improved movement desynchronization over the PSM cortex during movement execution but failed to improve impaired motor preparation. PET studies indicate that subthalamic nucleus (STN) stimulation partly reverses the abnormal premotor pattern of brain activation during movement. By monitoring MRD, we aimed to assess changes in premotor and PSM cortex oscillatory activity induced by bilateral STN stimulation and to compare these changes with those induced by l-dopa. Ten Parkinson's disease patients and a group of healthy, age-matched controls performed self-paced wrist flexions in each of four conditions: without either stimulation or l-dopa (the 'off' condition), with stimulation and without l-dopa (On Stim), with l-dopa and without stimulation ('on drug'), and with both stimulation and l-dopa (On Both). Compared with the Off condition, in both the On Stim and the On Drug condition the Unified Parkinson's Disease Rating Scale (UPDRS) III score decreased by about 60% and in the On Both condition it decreased by 80%. The desynchronization latency over central regions contralateral to movement and the movement desynchronization over bilateral central regions were significantly increased by stimulation and by l-dopa, with a maximal effect when the two were associated. Furthermore, desynchronization latency significantly decreased over bilateral frontocentral regions in the three treatment conditions compared with the Off condition. In Parkinson's disease, STN stimulation may induce a change in abnormal cortical oscillatory activity patterns (similar to that produced by l-dopa) by decreasing the abnormal spreading of desynchronization over frontocentral regions and increasing PSM cortex activity during movement

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

    PubMed

    Vanetsian, G L; Pavlova, I V

    2002-01-01

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

  17. Associative fear learning enhances sparse network coding in primary sensory cortex

    PubMed Central

    Gdalyahu, Amos; Tring, Elaine; Polack, Pierre-Olivier; Gruver, Robin; Golshani, Peyman; Fanselow, Michael S.; Silva, Alcino J.; Trachtenberg, Joshua T.

    2012-01-01

    Summary Several models of associative learning predict that stimulus processing changes during association formation. How associative learning reconfigures neural circuits in primary sensory cortex to "learn" associative attributes of a stimulus remains unknown. Using 2-photon in-vivo calcium imaging to measure responses of networks of neurons in primary somatosensory cortex, we discovered that associative fear learning, in which whisker stimulation is paired with foot shock, enhances sparse population coding and robustness of the conditional stimulus, yet decreases total network activity. Fewer cortical neurons responded to stimulation of the trained whisker than in controls, yet their response strength was enhanced. These responses were not observed in mice exposed to a non-associative learning procedure. Our results define how the cortical representation of a sensory stimulus is shaped by associative fear learning. These changes are proposed to enhance efficient sensory processing after associative learning. PMID:22794266

  18. [Functional asymmetry of electric processes in the rabbit brain cortex at formation of the hunger dominant].

    PubMed

    Rusinova, E V

    2011-01-01

    The motivational condition of hunger and formation of the hunger dominant after daily food deprivation was studied in the conditions of chronic experiments on rabbits. It was shown, that the hunger condition was accompanied by left sided interhemispher asymmetry on indicators of spectral capacity of EEG frontal and right-hand asymmetry sensorimotor areas of the cortex. A hunger dominant was accompanied by falling of spectral capacity of EEG of areas of both hemispheres. The condition of hunger and a hunger dominant were characterized by right-hand asymmetry on average level of EEG coherence of frontal and sensorimotor areas. At transition of a condition of hunger in a hunger dominant there was an average level of EEG coherence decrease in areas of the right hemisphere. Electric processes of the cortex of the brain at a motivational condition of hunger and a hunger dominant were different.

  19. Control of attention shifts between vision and audition in human cortex.

    PubMed

    Shomstein, Sarah; Yantis, Steven

    2004-11-24

    Selective attention contributes to perceptual efficiency by modulating cortical activity according to task demands. Visual attention is controlled by activity in posterior parietal and superior frontal cortices, but little is known about the neural basis of attentional control within and between other sensory modalities. We examined human brain activity during attention shifts between vision and audition. Attention shifts from vision to audition caused increased activity in auditory cortex and decreased activity in visual cortex and vice versa, reflecting the effects of attention on sensory representations. Posterior parietal and superior prefrontal cortices exhibited transient increases in activity that were time locked to the initiation of voluntary attention shifts between vision and audition. These findings reveal that the attentional control functions of posterior parietal and superior prefrontal cortices are not limited to the visual domain but also include the control of crossmodal shifts of attention.

  20. Electrophysiology of regular firing cells in the rat perirhinal cortex.

    PubMed

    D'Antuono, M; Biagini, G; Tancredi, V; Avoli, M

    2001-01-01

    The electrophysiological properties of neurons in the rat perirhinal cortex were analyzed with intracellular recordings in an in vitro slice preparation. Cells included in this study (n = 59) had resting membrane potential (RMP) = -73.9 +/- 8.5 mV (mean +/- SD), action potential amplitude = 95.5 +/- 10.4 mV, input resistance = 36.1 +/- v 15.7 M omega, and time constant = 13.9 +/- 3.4 ms. When filled with neurobiotin (n = 27) they displayed a pyramidal shape with an apical dendrite and extensive basal dendritic tree. Injection of intracellular current pulses revealed: 1) a tetrodotoxin (TTX, 1 microM)-sensitive, inward rectification in the depolarizing direction (n = 6), and 2) a time- and voltage-dependent hyperpolarizing sag that was blocked by extracellular Cs+ (3 mM, n = 5) application. Prolonged (up to 3 s) depolarizing pulses made perirhinal cells discharge regular firing of fast action potentials that diminished over time in frequency and reached a steady level (i.e., adapted). Repetitive firing was followed by an afterhyperpolarization that was decreased, along with firing adaptation, by the Ca(2+)-channel blocker Co2+ (2 mM, n = 6). Action potential broadening became evident during repetitive firing. This behavior, which was more pronounced when larger pulses of depolarizing current were injected (and thus when repetitive firing attained higher rates), was markedly decreased by Co2+ application. Subthreshold membrane oscillations at 5-12 Hz became apparent when cells were depolarized by 10-20 mV from RMP, and action potential clusters appeared with further depolarization. Application of glutamatergic and GABAA receptor antagonists (n = 4), CO2+ (n = 6), or Cs+ (n = 5) did not prevent the occurrence of these oscillations that were abolished by TTX (n = 6). Our results show that pyramidal-like neurons in the perirhinal cortex are regular firing cells with electrophysiological features resembling those of other cortical pyramidal elements. The ability to

  1. Dissociative contributions of the anterior cingulate cortex to apathy and depression: Topological evidence from resting-state functional MRI.

    PubMed

    Onoda, Keiichi; Yamaguchi, Shuhei

    2015-10-01

    Apathy is defined as a mental state characterized by a lack of goal-directed behavior. However, the underlying mechanisms of apathy remain to be fully understood. Apathy shares certain symptoms with depression and both these affective disorders are known to be associated with dysfunctions of the frontal cortex-basal ganglia circuits. It is expected that clarifying differences in neural mechanisms between the two conditions would lead to an improved understanding of apathy. The present study was designed to investigate whether apathy and depression depend on different network properties of the frontal cortex-basal ganglia circuits, by using resting state fMRI. Resting-state fMRI measurement and neuropsychological testing were conducted on middle-aged and older adults (N=392). Based on graph theory, we estimated nodal efficiency (functional integration), local efficiency (functional segregation), and betweenness centrality. We conducted multiple regression analyses for the network parameters using age, sex, apathy, and depression as predictors. Interestingly, results indicated that the anterior cingulate cortex showed lower nodal efficiency, local efficiency, and betweenness centrality in apathy, whereas in depression, it showed higher nodal efficiency and betweenness centrality. The anterior cingulate cortex constitutes the so-called "salience network", which detects salient experiences. Our results indicate that apathy is characterized by decreased salience-related processing in the anterior cingulate cortex, whereas depression is characterized by increased salience-related processing.

  2. Characterization of the Fiber Connectivity Profile of the Cerebral Cortex in Schizotypal Personality Disorder: A Pilot Study.

    PubMed

    Liu, Kai; Zhang, Teng; Zhang, Qing; Sun, Yueji; Wu, Jianlin; Lei, Yi; Chu, Winnie C W; Mok, Vincent C T; Wang, Defeng; Shi, Lin

    2016-01-01

    Schizotypal personality disorder (SPD) is considered one of the classic disconnection syndromes. However, the specific cortical disconnectivity pattern has not been fully investigated. In this study, we aimed to explore significant alterations in whole-cortex structural connectivity in SPD individuals (SPDs) by combining the techniques of brain surface morphometry and white matter tractography. Diffusion and structural MR data were collected from 20 subjects with SPD (all males; age, 19.7 ± 0.9 years) and 18 healthy controls (all males; age, 20.3 ± 1.0 years). To measure the structural connectivity for a given unit area of the cortex, the fiber connectivity density (FiCD) value was proposed and calculated as the sum of the fractional anisotropy of all the fibers connecting to that unit area in tractography. Then, the resultant whole-cortex FiCD maps were compared in a vertex-wise manner between SPDs and controls. Compared with normal controls, SPDs showed significantly decreased FiCD in the rostral middle frontal gyrus (crossing BA 9 and BA 10) and significantly increased FiCD in the anterior part of the fusiform/inferior temporal cortex (P < 0.05, Monte Carlo simulation corrected). Moreover, the gray matter volume extracted from the left rostral middle frontal cluster was observed to be significantly greater in the SPD group (P = 0.02). Overall, this study identifies a decrease in connectivity in the left middle frontal cortex as a key neural deficit at the whole-cortex level in SPD, thus providing insight into its neuropathological basis.

  3. Characterization of L-[3H]nicotine binding in human cerebral cortex: comparison between Alzheimer's disease and the normal.

    PubMed

    Flynn, D D; Mash, D C

    1986-12-01

    Putative nicotine receptors in the human cerebral cortex were characterized with L-[3H]nicotine, L-[3H]Nicotine binding was enhanced by the addition of Ca2+ and abolished in the presence of Na3EDTA. Association and dissociation of the ligand were rapid at 25 degrees C with t1/2 values of 2 and 3 min, respectively. Saturation binding analysis revealed an apparent single class of sites with a dissociation constant of 5.6 nM and a Hill coefficient of 1.05. There was no effect of postmortem interval on the density of binding sites assayed up to 24 h in rat frontoparietal cortex. Nicotine binding in human cortical samples was also unaltered by increasing sampling delay. In human cortical membranes, binding site density decreased with normal aging. Receptor affinity and concentration in samples of frontal cortex (Brodmann area 10) from patients with Alzheimer's disease were comparable to age-matched control values. Samples of infratemporal cortex (Brodmann area 38) from patients with Alzheimer's disease had a 50% reduction in the number of L-[3H]nicotine sites. Choline acetyltransferase activity was significantly decreased in both cortical areas. Enzyme activities in the temporal pole were reduced to 20% of control values. These data indicate that postsynaptic nicotine receptors are spared in the frontal cortex in Alzheimer's disease. In the infratemporal cortex, significant numbers of receptors remain despite the severe reduction in choline acetyltransferase activity. Replacement therapy directed at these sites may be warranted in Alzheimer's disease.

  4. Characterization of the Fiber Connectivity Profile of the Cerebral Cortex in Schizotypal Personality Disorder: A Pilot Study

    PubMed Central

    Liu, Kai; Zhang, Teng; Zhang, Qing; Sun, Yueji; Wu, Jianlin; Lei, Yi; Chu, Winnie C. W.; Mok, Vincent C. T.; Wang, Defeng; Shi, Lin

    2016-01-01

    Schizotypal personality disorder (SPD) is considered one of the classic disconnection syndromes. However, the specific cortical disconnectivity pattern has not been fully investigated. In this study, we aimed to explore significant alterations in whole-cortex structural connectivity in SPD individuals (SPDs) by combining the techniques of brain surface morphometry and white matter tractography. Diffusion and structural MR data were collected from 20 subjects with SPD (all males; age, 19.7 ± 0.9 years) and 18 healthy controls (all males; age, 20.3 ± 1.0 years). To measure the structural connectivity for a given unit area of the cortex, the fiber connectivity density (FiCD) value was proposed and calculated as the sum of the fractional anisotropy of all the fibers connecting to that unit area in tractography. Then, the resultant whole-cortex FiCD maps were compared in a vertex-wise manner between SPDs and controls. Compared with normal controls, SPDs showed significantly decreased FiCD in the rostral middle frontal gyrus (crossing BA 9 and BA 10) and significantly increased FiCD in the anterior part of the fusiform/inferior temporal cortex (P < 0.05, Monte Carlo simulation corrected). Moreover, the gray matter volume extracted from the left rostral middle frontal cluster was observed to be significantly greater in the SPD group (P = 0.02). Overall, this study identifies a decrease in connectivity in the left middle frontal cortex as a key neural deficit at the whole-cortex level in SPD, thus providing insight into its neuropathological basis. PMID:27303358

  5. Dysregulated but not decreased salience network activity in schizophrenia

    PubMed Central

    White, Thomas P.; Gilleen, James; Shergill, Sukhwinder S.

    2013-01-01

    Effective estimation of the salience of environmental stimuli underlies adaptive behavior, while related aberrance is believed to undermine rational thought processes in schizophrenia. A network including bilateral frontoinsular cortex (FIC) and dorsal anterior cingulate cortex (dACC) has been observed to respond to salient stimuli using functional magnetic resonance imaging (fMRI). To test the hypothesis that activity in this salience network (SN) is less discriminately modulated by contextually-relevant stimuli in schizophrenia than in healthy individuals, fMRI data were collected in 20 individuals with schizophrenia and 13 matched controls during performance of a modified monetary incentive delay (MID) task. After quantitatively identifying spatial components representative of the FIC and dACC features of the SN, two principal analyses were conducted. In the first, modulation of SN activity by salience was assessed by measuring response to trial outcome. First-level general linear models were applied to individual-specific time-courses of SN activity identified using spatial independent component analysis (ICA). This analysis revealed a significant salience-by-performance-by-group interaction on the best-fit FIC component's activity at trial outcome, whereby healthy individuals but not individuals with schizophrenia exhibited greater distinction between the response to hits and misses in high salience trials than in low salience trials. The second analysis aimed to ascertain whether SN component amplitude differed between the study groups over the duration of the experiment. Independent-samples T-tests on back-projected, percent-signal-change scaled SN component images importantly showed that the groups did not differ in the overall amplitude of SN expression over the entire dataset. These findings of dysregulated but not decreased SN activity in schizophrenia provide physiological support for mechanistic conceptual frameworks of delusional thought formation

  6. Clopidogrel Responsiveness in Patients Undergoing Peripheral Angioplasty

    SciTech Connect

    Pastromas, Georgios Spiliopoulos, Stavros Katsanos, Konstantinos Diamantopoulos, Athanasios Kitrou, Panagiotis Karnabatidis, Dimitrios Siablis, Dimitrios

    2013-12-15

    Purpose: To investigate the incidence and clinical significance of platelet responsiveness in patients receiving clopidogrel after peripheral angioplasty procedures. Materials and Methods: This prospective study included patients receiving antiplatelet therapy with clopidogrel 75 mg after infrainguinal angioplasty or stenting and who presented to our department during routine follow-up. Clopidogrel responsiveness was tested using the VerifyNow P2Y12 Assay. Patients with residual platelet reactivity units (PRU) {>=} 235 were considered as nonresponders (NR group NR), whereas patients with PRU < 235 were considered as normal (responders [group R]). Primary end points were incidence of resistance to clopidogrel and target limb reintervention (TLR)-free survival, whereas secondary end points included limb salvage rates and the identification of any independent predictors influencing clinical outcomes. Results: In total, 113 consecutive patients (mean age 69 {+-} 8 years) with 139 limbs were enrolled. After clopidogrel responsiveness analysis, 61 patients (53.9 %) with 73 limbs (52.5 %) were assigned to group R and 52 patients (46.1 %) with 66 limbs (47.5 %) to group NR. Mean follow-up interval was 27.7 {+-} 22.9 months (range 3-95). Diabetes mellitus, critical limb ischemia, and renal disease were associated with clopidogrel resistance (Fisher's exact test; p < 0.05). According to Kaplan-Meier analysis, TLR-free survival was significantly superior in group R compared with group NR (20.7 vs. 1.9 %, respectively, at 7-year follow-up; p = 0.001), whereas resistance to clopidogrel was identified as the only independent predictor of decreased TLR-free survival (hazard rate 0.536, 95 % confidence interval 0.31-0.90; p = 0.01). Cumulative TLR rate was significantly increased in group NR compared with group R (71.2 % [52 of 73] vs. 31.8 % [21 of 66], respectively; p < 0.001). Limb salvage was similar in both groups. Conclusion: Clopidogrel resistance was related with

  7. Body temperature effect on methylenedioxymethamphetamine-induced acute decrease in tryptophan hydroxylase activity.

    PubMed

    Che, S; Johnson, M; Hanson, G R; Gibb, J W

    1995-12-07

    Brain tryptophan hydroxylase activity decreases within 15 min after a single administration of 3,4-methylenedioxymethamphetamine. In the present study, the effect of body temperature on this acute decrease of tryptophan hydroxylase activity was examined. 2 h after a single dose of 3,4-methylenedioxymethamphetamine (20 mg/kg, s.c.), rats exhibited hyperthermia (38.7 degrees C) or hypothermia (35.8 degrees C) when maintained at 25 degrees C or 6 degrees C, respectively. The rectal temperature of control animals maintained at 6 degrees C was not altered. Tryptophan hydroxylase activity measured in the hippocampus, striatum and frontal cortex of hyperthermic rats treated with 3,4-methylenedioxymethamphetamine was decreased to 61%, 65%, and 71% of control levels, respectively, 2 h after drug treatment. However, in hypothermic rats, 3,4-methylenedioxymethamphetamine had no effect on tryptophan hydroxylase activity in the hippocampus, striatum or frontal cortex. Non-drug-induced hyperthermia or hypothermia did not affect tryptophan hydroxylase activity. Since hypothermia may prevent the 3,4-methylenedioxymethamphetamine-induced decrease in tryptophan hydroxylase activity by reducing the formation of free radicals, the effect of a free radical scavenging agent, N-tert-butyl-alpha-phenylnitrone, was examined. N-tert-butyl-alpha-phenylnitrone (200 mg/kg, i.p.) alone caused hypothermia but had no direct effect on tryptophan hydroxylase activity. Preadministration of N-tert-butyl-alpha-phenylnitrone prevented 3,4-methylenedioxymethamphetamine from raising the temperature above normal and attenuated the drug-induced decrease in tryptophan hydroxylase activity in hippocampus, striatum and frontal cortex. However, when the rats treated with a combination of N-tert-butyl-alpha-phenylnitrone and 3,4-methylenedioxymethamphetamine were maintained at hyperthermic conditions, N-tert-butyl-alpha-phenylnitrone had no protective effect. These results suggest that body temperature plays a

  8. Reduced Anterior Cingulate Cortex Glutamatergic Concentrations in Childhood Major Depression

    ERIC Educational Resources Information Center

    Mirza, Yousha; Tang, Jennifer; Russell, Aileen; Banerjee, S. Preeya; Bhandari, Rashmi; Ivey, Jennifer; Rose, Michelle; Moore, Gregory J.; Rosenberg, David R.

    2004-01-01

    Objective: To examine in vivo glutamatergic neurochemical alterations in the anterior cingulate cortex of children with major depressive disorder (MDD). Method: Single-voxel proton magnetic resonance spectroscopic ([.sup.1]H-MRS) examinations of the anterior cingulate cortex were conducted in 13 psychotropic-naive children and adolescents with MDD…

  9. Metaphorically Feeling: Comprehending Textural Metaphors Activates Somatosensory Cortex

    ERIC Educational Resources Information Center

    Lacey, Simon; Stilla, Randall; Sathian, K.

    2012-01-01

    Conceptual metaphor theory suggests that knowledge is structured around metaphorical mappings derived from physical experience. Segregated processing of object properties in sensory cortex allows testing of the hypothesis that metaphor processing recruits activity in domain-specific sensory cortex. Using functional magnetic resonance imaging…

  10. Olfactocentric Paralimbic Cortex Morphology in Adolescents with Bipolar Disorder

    ERIC Educational Resources Information Center

    Wang, Fei; Kalmar, Jessica H.; Womer, Fay Y.; Edmiston, Erin E.; Chepenik, Lara G.; Chen, Rachel; Spencer, Linda; Blumberg, Hilary P.

    2011-01-01

    The olfactocentric paralimbic cortex plays a critical role in the regulation of emotional and neurovegetative functions that are disrupted in core features of bipolar disorder. Adolescence is thought to be a critical period in both the maturation of the olfactocentric paralimbic cortex and in the emergence of bipolar disorder pathology. Together,…

  11. Insular Cortex Is Involved in Consolidation of Object Recognition Memory

    ERIC Educational Resources Information Center

    Bermudez-Rattoni, Federico; Okuda, Shoki; Roozendaal, Benno; McGaugh, James L.

    2005-01-01

    Extensive evidence indicates that the insular cortex (IC), also termed gustatory cortex, is critically involved in conditioned taste aversion and taste recognition memory. Although most studies of the involvement of the IC in memory have investigated taste, there is some evidence that the IC is involved in memory that is not based on taste. In…

  12. Successful cryopreservation of human ovarian cortex tissues using supercooling.

    PubMed

    Moriguchi, Hisashi; Zhang, Yue; Mihara, Makoto; Sato, Chifumi

    2012-01-01

    The development of new method to cryopreserve human ovarian cortex tissues without damage is needed for the improvement of quality of life (QOL) of female cancer patients. Here we show novel cryopreservation method of human ovarian cortex tissues by using supercooling (S.C.) procedure. Our method will be helpful in order to preserve fertility of female cancer patients.

  13. Activity in Prelimbic Cortex Subserves Fear Memory Reconsolidation over Time

    ERIC Educational Resources Information Center

    Stern, Cristina A. J.; Gazarini, Lucas; Vanvossen, Ana C.; Hames, Mayara S.; Bertoglio, Leandro J.

    2014-01-01

    The prelimbic cortex has been implicated in the consolidation of previously learned fear. Herein, we report that temporarily inactivating this medial prefrontal cortex subregion with the GABA [subscript A] agonist muscimol (4.0 nmol in 0.2 µL per hemisphere) was able to equally disrupt 1-, 7-, and 21-d-old contextual fear memories after their…

  14. Medial Prefrontal Cortex Lesions Abolish Contextual Control of Competing Responses

    ERIC Educational Resources Information Center

    Haddon, J. E.; Killcross, A. S.

    2005-01-01

    There is much debate as to the extent and nature of functional specialization within the different subregions of the prefrontal cortex. The current study was undertaken to investigate the effect of damage to medial prefrontal cortex subregions in the rat. Rats were trained on two biconditional discrimination tasks, one auditory and one visual, in…

  15. Dynamic neuroplasticity after human prefrontal cortex damage.

    PubMed

    Voytek, Bradley; Davis, Matar; Yago, Elena; Barceló, Francisco; Vogel, Edward K; Knight, Robert T

    2010-11-04

    Memory and attention deficits are common after prefrontal cortex (PFC) damage, yet people generally recover some function over time. Recovery is thought to be dependent upon undamaged brain regions, but the temporal dynamics underlying cognitive recovery are poorly understood. Here, we provide evidence that the intact PFC compensates for damage in the lesioned PFC on a trial-by-trial basis dependent on cognitive load. The extent of this rapid functional compensation is indexed by transient increases in electrophysiological measures of attention and memory in the intact PFC, detectable within a second after stimulus presentation and only when the lesioned hemisphere is challenged. These observations provide evidence supporting a dynamic and flexible model of compensatory neural plasticity.

  16. The cerebral cortex in fetal Down syndrome.

    PubMed

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

    2003-01-01

    Brain histopathology of 32 fetuses with Down syndrome was compared to that of 25 age-matched normal con