Agranular Insula

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Joseph L Price - One of the best experts on this subject based on the ideXlab platform.

  • architectonic subdivision of the human orbital and medial prefrontal cortex
    The Journal of Comparative Neurology, 2003
    Co-Authors: Dost Ongur, Amon T Ferry, Joseph L Price
    Abstract:

    The structure of the human orbital and medial prefrontal cortex (OMPFC) was investigated using five histological and immunohistochemical stains and was correlated with a previous analysis in macaque monkeys [Carmichael and Price (1994) J. Comp. Neurol. 346:366–402]. A cortical area was recognized if it was distinct with at least two stains and was found in similar locations in different brains. All of the areas recognized in the macaque OMPFC have counterparts in humans. Areas 11, 13, and 14 were subdivided into areas 11m, 11l, 13a, 13b, 13m, 13l, 14r, and 14c. Within area 10, the region corresponding to area 10m in monkeys was divided into 10m and 10r, and area 10o (orbital) was renamed area 10p (polar). Areas 47/12r, 47/12m, 47/12l, and 47/12s occupy the lateral orbital cortex, corresponding to monkey areas 12r, 12m, 12l, and 12o. The Agranular Insula (areas Iam, Iapm, Iai, and Ial) extends onto the caudal orbital surface and into the horizontal ramus of the lateral sulcus. The growth of the frontal pole in humans has pushed area 25 and area 32pl, which corresponds to the prelimbic area 32 in Brodmann's monkey brain map, caudal and ventral to the genu of the corpus callosum. Anterior cingulate areas 24a and 24b also extend ventral to the genu of the corpus callosum. Area 32ac, corresponding to the dorsal anterior cingulate area 32 in Brodmann's human brain map, is anterior and dorsal to the genu. The parallel organization of the OMPFC in monkeys and humans allows experimental data from monkeys to be applied to studies of the human cortex. J. Comp. Neurol. 460:425–449, 2003. © 2003 Wiley-Liss, Inc.

  • prefrontal cortical projections to the hypothalamus in macaque monkeys
    The Journal of Comparative Neurology, 1998
    Co-Authors: Dost Ongur, X An, Joseph L Price
    Abstract:

    The organization of projections from the macaque orbital and medial prefrontal cortex (OMPFC) to the hypothalamus and related regions of the diencephalon and midbrain was studied with retrograde and anterograde tracing techniques. Almost all of the prefrontal cortical projections to the hypothalamus arise from areas within the ‘‘medial prefrontal network,’’ as defined previously by Carmichael and Price ([1996] J. Comp. Neurol. 371:179‐ 207). Outside of the OMPFC, only a few neurons in the temporal pole, anterior cingulate and Insular cortex project to the hypothalamus. Axons from the OMPFC also innervate the basal forebrain, zona incerta, and ventral midbrain. Within the medial prefrontal network, different regions project to distinct parts of the hypothalamus. The medial wall areas 25 and 32 send the heaviest projections to the hypothalamus; axons from these areas are especially concentrated in the anterior hypothalamic area and the ventromedial hypothalamic nucleus. Orbital areas 13a, 12o, and Iai, which are related to the medial prefrontal network, selectively innervate the lateral hypothalamic area, especially its posterior part. The cellular regions of the paraventricular, supraoptic, suprachiasmatic, arcuate, and mammillary nuclei are conspicuously devoid of cortical axons, but many axons abut the borders of these nuclei and may contact dendrites that extend from them. Areas within the orbital prefrontal network on the posterior orbital surface and Agranular Insula send only weak projections to the posterior lateral hypothalamic area. The rostral orbital surface does not contribute to the cortico-hypothalamic projection. J. Comp.

  • architectonic subdivision of the orbital and medial prefrontal cortex in the macaque monkey
    The Journal of Comparative Neurology, 1994
    Co-Authors: S T Carmichael, Joseph L Price
    Abstract:

    The orbital and medial prefrontal cortex (OMPFC) of macaque monkeys is a large but little understood region of the cerebral cortex. In this study the architectonic structure of the OMPFC was analyzed with nine histochemical and immunohistochemical stains in 32 individuals of three macaque species. The stains included Nissl, myelin, acetylcholinesterase, Timm, and selenide stains and immunohistochemical stains for parvalbumin, calbindin, a nonphosphorylated neurofilament epitope (with the SMI-32 antibody), and a membrane-bound glycoprotein (with the 8b3 antibody). In addition to patterns of cell bodies and myelinated fibers, these techniques allow the visualization of markers related to metabolism, synapses, and neurotransmitters. A cortical area was defined as distinct if it was differentiated in at least three different stains and, as described in later papers, possessed a distinct set of connections. Twenty-two areas were recognized in the OMPFC. Walker's areas 10, 11, 12, 13, and 14 [J. Comp. Neurol. (1940) 73:59-86] have been subdivided into areas 10m, 10o, 11m, 11l, 12r, 12l, 12m, 12o, 13m, 13l, 13a, 13b, 14r, and 14c. On the medial wall, areas 32, 25, and 24a,b,c have been delineated, in addition to area 10m. The Agranular Insula also has been recognized to extend onto the posterior orbital surface and has been subdivided into medial, intermediate, lateral, posteromedial, and posterolateral Agranular Insula areas. The OMPFC, therefore, resembles other areas of primate cortex, such as the posterior parietal and temporal cortices, where a large number of relatively small, structurally and connectionally distinct areas have been recognized. Just as the area-specific neurophysiological properties of these parietotemporal areas underlie broader regional functions such as visuospatial analysis, it is likely that the many small areas of the OMPFC also make differential contributions to the general mnemonic, sensory, and affective functions of this region.

  • Central Olfactory Connections in the Macaque Monkey
    The Journal of comparative neurology, 1994
    Co-Authors: S T Carmichael, M.-c. Clugnet, Joseph L Price
    Abstract:

    The connections between the olfactory bulb, primary olfactory cortex, and olfactory related areas of the orbital cortex were defined in macaque monkeys with a combination of anterograde and retrograde axonal tracers and electrophysiological recording. Anterograde tracers placed into the olfactory bulb labeled axons in eight primary olfactory cortical areas: the anterior olfactory nucleus, piriform cortex, ventral tenia tecta, olfactory tubercle, anterior cortical nucleus of the amygdala, periamygdaloid cortex, and olfactory division of the entorhinal cortex. The bulbar axons terminate in the outer part of layer I throughout these areas and are most dense in areas that are close to the lateral olfactory tract. Labeled axons also were found in the superficial part of nucleus of the horizontal diagonal band. Retrograde tracers injected into the olfactory bulb labeled cells in the nucleus of the diagonal band and in all of the primary olfactory cortical areas except the olfactory tubercle. Electrical stimulation of the olfactory bulb evoked short-latency unit responses and a characteristic field wave in the primary olfactory cortex. Multiunit activity in layer II tended to be of shorter latency than that in layer III and the endopiriform nucleus. Associational connections within the primary olfactory cortex were demonstrated with anterograde tracer injections into the piriform cortex and the entorhinal cortex. Injections into the piriform cortex near the lateral olfactory tract labeled axons in the deep part of layer I of many primary olfactory areas, but especially in areas near the tract. An injection into the rostral entorhinal cortex, distant to the lateral olfactory tract, labeled a complementary distribution of axons in deep layer I of olfactory areas medial and caudoventral to the tract. This organization resembles that reported in the primary olfactory cortex of the rat [Luskin and Price (1983) J. Comp. Neurol. 216:264-291]. The anterograde tracer injections into the piriform cortex and retrograde tracer injections into the orbital and medial prefrontal cortex and rostral Insula label connections from the primary olfactory cortex to nine areas in the caudal orbital cortex, including the Agranular Insula areas Iam, Iai, Ial, Iapm, and Iapl and areas 14c, 25, 13a, and 13m. The piriform cortex projects most heavily to layer I of these areas. Only Iam, Iapm, and 13a receive a substantial projection to the deeper layers. Areas Iam, Iapm, and 13a were also the only areas that responded with multiunit action potentials to olfactory bulb stimulation in anesthetized animals.(ABSTRACT TRUNCATED AT 400 WORDS)

Edmund T. Rolls - One of the best experts on this subject based on the ideXlab platform.

  • Age differences in the brain mechanisms of good taste
    NeuroImage, 2015
    Co-Authors: Edmund T. Rolls, Michele B. Kellerhals, Thomas E. Nichols
    Abstract:

    There is strong evidence demonstrating age-related differences in the acceptability of foods and beverages. To examine the neural foundations underlying these age-related differences in the acceptability of different flavors and foods, we performed an fMRI study to investigate brain and hedonic responses to orange juice, orange soda, and vegetable juice in three different age groups: Young (22), Middle (40) and Elderly (60 years). Orange juice and orange soda were found to be liked by all age groups, while vegetable juice was disliked by the Young, but liked by the Elderly. In the Insular primary taste cortex, the activations to these stimuli were similar in the 3 age groups, indicating that the differences in liking for these stimuli between the 3 groups were not represented in this first stage of cortical taste processing. In the Agranular Insula (anterior to the Insular primary taste cortex) where flavor is represented, the activations to the stimuli were similar in the Elderly, but in the Young the activations were larger to the vegetable juice than to the orange drinks; and the activations here were correlated with the unpleasantness of the stimuli. In the anterior midcingulate cortex, investigated as a site where the activations were correlated with the unpleasantness of the stimuli, there was again a greater activation to the vegetable than to the orange stimuli in the Young but not in the Elderly. In the amygdala (and orbitofrontal cortex), investigated as sites where the activations were correlated with the pleasantness of the stimuli, there was a smaller activation to the vegetable than to the orange stimuli in the Young but not in the Elderly. The Middle group was intermediate with respect to the separation of their activations to the stimuli in the brain areas that represent the pleasantness or unpleasantness of flavors. Thus age differences in the activations to different flavors can in some brain areas be related to, and probably cause, the differences in pleasantness of foods as they differ for people of different ages. This novel work provides a foundation for understanding the underlying neural bases for differences in food acceptability between age groups.

  • Neural systems underlying decisions about affective odors
    Journal of cognitive neuroscience, 2010
    Co-Authors: Edmund T. Rolls, Fabian Grabenhorst, Benjamin A. Parris
    Abstract:

    Decision-making about affective value may occur after the reward value of a stimulus is represented and may involve different brain areas to those involved in decision-making about the physical properties of stimuli, such as intensity. In an fMRI study, we delivered two odors separated by a delay, with instructions on different trials to decide which odor was more pleasant or more intense or to rate the pleasantness and intensity of the second odor without making a decision. The fMRI signals in the medial prefrontal cortex area 10 (medial PFC) and in regions to which it projects, including the anterior cingulate cortex (ACC) and Insula, were higher when decisions were being made compared with ratings, implicating these regions in decision-making. Decision-making about affective value was related to larger signals in the dorsal part of medial area 10 and the Agranular Insula, whereas decisions about intensity were related to larger activations in the dorsolateral prefrontal cortex (dorsolateral PFC), ventral premotor cortex, and anterior Insula. For comparison, the mid orbitofrontal cortex (OFC) had activations related not to decision-making but to subjective pleasantness ratings, providing a continuous representation of affective value. In contrast, areas such as medial area 10 and the ACC are implicated in reaching a decision in which a binary outcome is produced.

  • Taste-olfactory convergence, and the representation of the pleasantness of flavour
    2003
    Co-Authors: Ivan E. T. De Araujo, Edmund T. Rolls, Morten L. Kringelbach, Francis Mcglone, Nicola Phillips
    Abstract:

    The functional architecture of the central taste and olfactory systems in primates provides evidence that the convergence of taste and smell information onto single neurons is realized in the caudal orbitofrontal cortex (and immediately adjacent Agranular Insula). These higher-order association cortical areas thus support ¯avour processing. Much less is known, however, about homologous regions in the human cortex, or how taste±odour interactions, and thus ¯avour perception, are implemented in the human brain. We performed an event-related fMRI study to investigate where in the human brain these interactions between taste and odour stimuli (administered retronasally) may be realized. The brain regions that were activated by both taste and smell included parts of the caudal orbitofrontal cortex, amygdala, Insular cortex and adjoining areas, and anterior cingulate cortex. It was shown that a small part of the anterior (putatively Agranular) Insula responds to unimodal taste and to unimodal olfactory stimuli, and that a part of the anterior frontal operculum is a unimodal taste area (putatively primary taste cortex) not activated by olfactory stimuli. Activations to combined olfactory and taste stimuli where there was little or no activation to either alone (providing positive evidence for interactions between the olfactory and taste inputs) were found in a lateral anterior part of the orbitofrontal cortex. Correlations with consonance ratings for the smell and taste combinations, and for their pleasantness, were found in a medial anterior part of the orbitofrontal cortex. These results provide evidence on the neural substrate for the convergence of taste and olfactory stimuli to produce ¯avour in humans, and where th

  • Taste-olfactory convergence, and the representation of the pleasantness of flavour, in the human brain
    The European journal of neuroscience, 2003
    Co-Authors: Ivan E. T. De Araujo, Edmund T. Rolls, Morten L. Kringelbach, Francis Mcglone, Nicola Phillips
    Abstract:

    The functional architecture of the central taste and olfactory systems in primates provides evidence that the convergence of taste and smell information onto single neurons is realized in the caudal orbitofrontal cortex (and immediately adjacent Agranular Insula). These higher-order association cortical areas thus support flavour processing. Much less is known, however, about homologous regions in the human cortex, or how taste-odour interactions, and thus flavour perception, are implemented in the human brain. We performed an event-related fMRI study to investigate where in the human brain these interactions between taste and odour stimuli (administered retronasally) may be realized. The brain regions that were activated by both taste and smell included parts of the caudal orbitofrontal cortex, amygdala, Insular cortex and adjoining areas, and anterior cingulate cortex. It was shown that a small part of the anterior (putatively Agranular) Insula responds to unimodal taste and to unimodal olfactory stimuli, and that a part of the anterior frontal operculum is a unimodal taste area (putatively primary taste cortex) not activated by olfactory stimuli. Activations to combined olfactory and taste stimuli where there was little or no activation to either alone (providing positive evidence for interactions between the olfactory and taste inputs) were found in a lateral anterior part of the orbitofrontal cortex. Correlations with consonance ratings for the smell and taste combinations, and for their pleasantness, were found in a medial anterior part of the orbitofrontal cortex. These results provide evidence on the neural substrate for the convergence of taste and olfactory stimuli to produce flavour in humans, and where the pleasantness of flavour is represented in the human brain.

Nicola Phillips - One of the best experts on this subject based on the ideXlab platform.

  • Taste-olfactory convergence, and the representation of the pleasantness of flavour
    2003
    Co-Authors: Ivan E. T. De Araujo, Edmund T. Rolls, Morten L. Kringelbach, Francis Mcglone, Nicola Phillips
    Abstract:

    The functional architecture of the central taste and olfactory systems in primates provides evidence that the convergence of taste and smell information onto single neurons is realized in the caudal orbitofrontal cortex (and immediately adjacent Agranular Insula). These higher-order association cortical areas thus support ¯avour processing. Much less is known, however, about homologous regions in the human cortex, or how taste±odour interactions, and thus ¯avour perception, are implemented in the human brain. We performed an event-related fMRI study to investigate where in the human brain these interactions between taste and odour stimuli (administered retronasally) may be realized. The brain regions that were activated by both taste and smell included parts of the caudal orbitofrontal cortex, amygdala, Insular cortex and adjoining areas, and anterior cingulate cortex. It was shown that a small part of the anterior (putatively Agranular) Insula responds to unimodal taste and to unimodal olfactory stimuli, and that a part of the anterior frontal operculum is a unimodal taste area (putatively primary taste cortex) not activated by olfactory stimuli. Activations to combined olfactory and taste stimuli where there was little or no activation to either alone (providing positive evidence for interactions between the olfactory and taste inputs) were found in a lateral anterior part of the orbitofrontal cortex. Correlations with consonance ratings for the smell and taste combinations, and for their pleasantness, were found in a medial anterior part of the orbitofrontal cortex. These results provide evidence on the neural substrate for the convergence of taste and olfactory stimuli to produce ¯avour in humans, and where th

  • Taste-olfactory convergence, and the representation of the pleasantness of flavour, in the human brain
    The European journal of neuroscience, 2003
    Co-Authors: Ivan E. T. De Araujo, Edmund T. Rolls, Morten L. Kringelbach, Francis Mcglone, Nicola Phillips
    Abstract:

    The functional architecture of the central taste and olfactory systems in primates provides evidence that the convergence of taste and smell information onto single neurons is realized in the caudal orbitofrontal cortex (and immediately adjacent Agranular Insula). These higher-order association cortical areas thus support flavour processing. Much less is known, however, about homologous regions in the human cortex, or how taste-odour interactions, and thus flavour perception, are implemented in the human brain. We performed an event-related fMRI study to investigate where in the human brain these interactions between taste and odour stimuli (administered retronasally) may be realized. The brain regions that were activated by both taste and smell included parts of the caudal orbitofrontal cortex, amygdala, Insular cortex and adjoining areas, and anterior cingulate cortex. It was shown that a small part of the anterior (putatively Agranular) Insula responds to unimodal taste and to unimodal olfactory stimuli, and that a part of the anterior frontal operculum is a unimodal taste area (putatively primary taste cortex) not activated by olfactory stimuli. Activations to combined olfactory and taste stimuli where there was little or no activation to either alone (providing positive evidence for interactions between the olfactory and taste inputs) were found in a lateral anterior part of the orbitofrontal cortex. Correlations with consonance ratings for the smell and taste combinations, and for their pleasantness, were found in a medial anterior part of the orbitofrontal cortex. These results provide evidence on the neural substrate for the convergence of taste and olfactory stimuli to produce flavour in humans, and where the pleasantness of flavour is represented in the human brain.

Evrard H. - One of the best experts on this subject based on the ideXlab platform.

  • Insular projections to brainstem homeostatic centers in the macaque monkey
    'Frontiers Media SA', 2017
    Co-Authors: Saleh T., Logothetis N., Evrard H.
    Abstract:

    The large spindle-shaped von Economo neuron (VEN) occurs in a specific architectonic area (‘VEN-area’) in the macaque anterior Insula (Evrard et al., Neuron, 2012, 74:482-9). Given its relatively large size and localization in layer 5a, the VEN likely projects to distant brain regions including the midbrain periaqueductal gray (PAG) and the parabrachial nucleus (PBN). PBN and PAG have a crucial role in gating interoceptive afferents, and in patterning physiological and behavioral emotional responses. We examined the distribution of neurons retrogradely labeled in the Insula with injections of cholera toxin b, fast blue or fluorescent dextran in different columns of PAG or in PBN. Injections in PAG invariably labeled small, discontinuous patches of neurons in the ventral portion of the Insula as well as in the medial prefrontal cortex. Using a refined architectonic map of the Insula (Evrard et al., J Comp Neurol, 2014, 522:64–97), we observed that the areal affiliation of these patches consistently varied with the location of the injection. Injections in the dorsal lateral column of PAG (dlPAG) sparsely labeled distinct areas posterior to the limen, and densely labeled the intermediate Agranular area (Iai), anterior to the limen. Injections in the lateral column of PAG (lPAG) labeled the ‘mound’ dysgranular area (Idm) and the dorsal posterior Agranular area (Iapd), posterior to the limen, and the lateral Agranular Insula (Ial), anterior to the limen. Injections in the ventrolateral column of PAG (vlPAG) labeled both Iai and Ial. In stark contrast with injections in PAG, injections in PBN labeled almost exclusively the very anterior Insular areas including Iai and Ial. The rest of the Insula and the medial prefrontal cortex lacked labeling. VENs and fork cells were located almost exclusively in Ial and were retrogradely labeled from injections in lPAG, vlPAG, and PBN. The projection of directly adjacent Insular areas to different columns of PAG may provide a unique insight in the cortical control of the autonomous system. The selective projection to PBN substantiates our prior evidence for a functional link between PBN and the VEN area in coma (Fischer et al., Neurology, 2016, 90:143-51). In this context, the VEN and their companion FC could have a direct and rapid influence on the autonomic substrate of emotional behavior and conscious awareness of feelings

  • A human brain network linking arousal to awareness
    2015
    Co-Authors: Fischer D., Evrard H., Boes A., Demertzi A., Laureys S., Edlow B., Saper C., Pascual-leone A., Fox M., Geerling J.
    Abstract:

    OBJECTIVE: Arousal, or wakefulness, is a fundamental brain process on which all cognitive functions rely, and which has important clinical applications. However, the neurobiology of arousal in humans remains incompletely characterized. The underlying neuroanatomy can be studied through focal lesions that induce coma, with evidence suggesting that such lesions commonly involve the pontine tegmentum. However, the precise location of the brainstem region critical for arousal remains unclear. Furthermore, the brainstem is thought to promote arousal through ascending projections to a distributed network, but the nodes of this network in humans are poorly defined. METHODS: To identify the brainstem region critical for arousal and its associated network in humans, we integrated a lesion overlap analysis with resting state functional connectivity MRI (rs-fcMRI). We collected 36 focal brainstem lesions: 12 lesions caused coma, and 24 control lesions caused motor deficits with preservation of consciousness/arousal. By overlapping the coma lesions and subtracting the control lesions, we identified a coma-specific region of the brainstem. We then used rs-fcMRI collected from 98 healthy individuals to identify the functionally connected network of this coma-specific region. RESULTS: The coma-specific region of the brainstem localized to the lateral pontine tegmentum, overlying the medial parabrachial nucleus (PB). The rs-fcMRI analysis revealed two functionally connected nodes: the Agranular Insula (AI) and anterior cingulate cortex (ACC). These regions exhibited significantly more connectivity to coma lesions than control lesions. Based on connectivity to the AI and ACC, the PB most closely resembled the coma-specific region, compared to other nearby nuclei. CONCLUSIONS: Coma-causing lesions appear to involve the PB, which exhibits connectivity to the AI and ACC in a three-node network. Damage to the PB region may therefore be integral to the pathophysiology of coma; as the PB is critical to arousal in non-human animals, our findings suggest a homologous neural system of arousal between animals and humans. The AI and ACC are the primary sites of Von Economo neurons, and have been implicated in conscious awareness in humans. Our findings therefore link a brainstem nucleus of arousal to cortical regions associated with human awareness, offering a neural basis for integration of these two processes

  • Projections of the orbital and medial prefrontal cortex to the ventral tegmental area in the macaque monkey
    2014
    Co-Authors: Hernandez-mombiela D., Logothetis N., Ubero M., Price J., Evrard H.
    Abstract:

    The orbital and medial prefrontal cortex (OMPFC) in macaque monkeys sends discreet glutamatergic projections to the ventral tegmental area (VTA) (Ongür et al., J Comp Neurol, 1998, 401:480-505; Frankle et al., Neuropsychopharmacol, 2006, 31:1627-36). These projections likely provide a mild direct influence on VTA activity, in addition to a stronger indirect influence involving intermediary glutamatergic diencephalic nuclei. On the basis of its connectivity, OMPFC has been divided into orbital ‘sensory’ (OPFC) and medial ‘visceromotor’ (MPFC) networks (Price, ANYAS, 2007, 1121:54-71). Projections to VTA originate from both networks but whether their density varies across areas within a single network and whether they are topographically organized within VTA remain unknown. Here, we examined (1) the distribution of anterograde labeling produced in VTA with injections of biotin dextran amine or fluororuby in distinct architectonic areas in OPFC and MPFC, and (2) the distribution of retrograde labeling produced in PFC with injections of cholera toxin b or fluorescent dextran in VTA. The analysis of the anterograde labeling confirmed prior evidence that PFC contributes only moderate projections to VTA, in contrast with their projections to other targets (e.g. striatum). The density of anterogradely labeled fibers with varicosities in VTA varied with the location of the injection site, so that each network had areas contributing more projections than others. Injections in the medial network produced overall more labeling than injection in the orbital network. Injections in areas 25, 24b, 32, and the intermediate Agranular Insula (Iai) produced relatively dense labeling. In contrast, injections in areas 10o, 11m and 14c produced sparse or no labeling. In the orbital network, only injections in area 13b and in the posterior median Agranular Insula (Iapm) produced relatively dense labeling with no major difference between areas. Injections in all the other areas including areas 13l, 11l, 12m, 12r and 12l produced sparse or no labeling. A comparison of the spatial distribution of the labeled fibers in VTA revealed a considerable overlap of the projections from the different areas with only a subtle trend for medial projections to terminate more lateral and rostral than orbital projections. Retrograde tracers injections in VTA supported the heterogeneity of the areal distribution of the cells of origin of PFC projections to VTA. Large injections preferentially labeled areas from which dense labeling was obtained in VTA. Smaller injections tended to label only a subset of these areas supporting the existence of a discreet internal topography within VTA

  • Anterograde and retrograde analysis of the connections between the orbital and medial prefrontal cortex and the locus coeruleus in the macaque monkey
    2014
    Co-Authors: Ubero M., Logothetis N., Hernandez D., Price J., Insausti R., Evrard H.
    Abstract:

    Prior dopamine-beta-hydroxylase immunohistochemistry suggested that the projections from the locus coeruleus (LC) to the orbital and medial prefrontal cortex (PFC) are heterogeneous (Lewis & Morrison, J Comp Neurol, 1989, 282:317-30). A tract-tracing corroboration of this heterogeneity is still lacking. In addition, whether areas of PFC that receive direct projections from LC are the same that provide modulatory feedback to LC remains unclear. Here, we examined the distribution of retrograde and anterograde labeling in LC with injections of multiple, differently-colored neuronal tracers in distinct architectonic areas in orbital and medial PFC. On the basis of its connectivity, the orbital and medial PFC was divided into orbital (OPFC) and medial (MPFC) ‘networks’ (Price, ANYAS, 2007, 1121:54-71). Injections of retrograde tracers in PFC produced dense to sparse labeling in the LC core. The distribution of this labeling varied with the location of the injection site, supporting the prior immunohistochemical evidence. In the MPFC network, injections in areas 24, 25, 32, 10, 14c, and the intermediate Agranular Insula (Iai) produced a moderate to dense labeling in LC, with injections in areas 24, 25 and 32 producing the densest labeling, and with injection in area 10m producing more labeling than injection in area 10o. In the OPFC network, injections in area 13b, 12l, and the posterior median Agranular Insula (Iapm) produced dense labeling in LC whereas injections in area 11l produced only sparse labeling. The distribution of retrograde labeling in LC revealed a conspicuous overlap of cells labeled from distinct areas, with no obvious internal topography. Despite this conspicuous overlap, no double labeled cells could be observed in cases with injections of differently-colored tracers in distinct areas. This absence of co-localization is consistent with similar recent evidence obtained in rats (Chandler & Waterhouse, Front Behav Neurosci, 2012, 6:1-9) and suggests a complex spatial segregation of LC projecting neurons. The injection of anterograde tracers in PFC produced dense to sparse labeling predominantly in the direct periphery of the LC core. The examination of the distribution of this labeling indicated that the connections between LC and the different areas of OPFC and MPFC are rather reciprocal. In the MPFC network, injections in areas 24, 25, 32, 11m and Iai produced dense labeling whereas injections in 10m and 10o produced moderate and no labeling, respectively. In the OPFC network, injections in area 13l, Iapm, and the medial Agranular Insula (Iam) produced dense labeling whereas injections in areas 11l produced sparse labeling

  • Insular projections to the midbrain periaqueductal gray in the macaque monkey
    2014
    Co-Authors: Saleh T., Logothetis N., Price J., Evrard H.
    Abstract:

    We recently demonstrated the presence of the large spindle-shaped von Economo neuron (VEN) in a specific architectonic area (‘VEN-area’) in the anterior Insula in the macaque monkey (Evrard et al., Neuron, 2012, 74:482-9). Given its relatively large size and localization in layer 5a, the VEN likely projects to distant brain regions including the midbrain periaqueductal gray (PAG). A prior tracing study demonstrated that distinct areas in the macaque anterior Insula project densely to PAG (An et al., J Comp Neurol, 1998, 401:455-79). Here, using previously published (An et al., 1998) and new material, we examined (1) the distribution of neurons retrogradely labeled in the Insula with injections of cholera toxin b, fast blue or fluorescent dextran in different columns of PAG, (2) whether any of the architectonic areas projecting to PAG corresponds to the VEN-area, and (3) whether the VEN and its co-mingled companion ‘fork’ cell (FC) project to PAG. Injections in PAG invariably labeled small, discontinuous patches of neurons in the ventral portion of the Insula both posterior and anterior to the limen Insula. Using a recently refined architectonic map of the macaque Insula (Evrard et al., J Comp Neurol, 2014, 522:64-97), we observed that the areal affiliation of these patches consistently varied with the location of the injection site. Injections in the dorsal lateral column of PAG (dlPAG) sparsely labeled the fundal Agranular area (Ivfa), and the dorsal and ventral posterior Agranular areas (Iapd and Iapv), posterior to the limen, and densely labeled the intermediate Agranular area (Iai), anterior to the limen, as reported before by An et al. (1998). Injections in the lateral column of PAG (lPAG) labeled the ‘mound’ dysgranular area (Idm) and the dorsal posterior Agranular area (Iapd), posterior to the limen, and the lateral Agranular Insula (Ial), anterior to the limen. Injections in the ventrolateral column of PAG (vlPAG) produced an intermediate labeling including both Iai and Ial. VENs and fork cells were located preferentially, if not exclusively, in Ial. An analysis of the morphology of the neurons retrogradely labeled in Ial revealed a small subset of VENs and fork cells. The projection of directly adjacent Insular areas to different columns of PAG may provide a unique insight in the efferent cortical control of the autonomous system. In this context, the VEN and their companion FC could have a direct and rapid influence on the sympathetic and parasympathetic substrate of emotional behavior and feelings

W. D. J. Van De Berg - One of the best experts on this subject based on the ideXlab platform.

  • Differential Insular cortex subregional vulnerability to α-synuclein pathology in Parkinson's disease and dementia with Lewy bodies
    Neuropathology and applied neurobiology, 2018
    Co-Authors: Yasmine Y. Fathy, A.j. Jonker, E. Oudejans, F.j.j. De Jong, A.m.w. Van Dam, Annemieke J.m. Rozemuller, W. D. J. Van De Berg
    Abstract:

    Aim: The Insular cortex consists of a heterogenous cytoarchitecture and diverse connections and is thought to integrate autonomic, cognitive, emotional and interoceptive functions to guide behaviour. In Parkinson's disease (PD) and dementia with Lewy bodies (DLB), it reveals α-synuclein pathology in advanced stages. The aim of this study is to assess the Insular cortex cellular and subregional vulnerability to α-synuclein pathology in well-characterized PD and DLB subjects. Methods: We analysed postmortem Insular tissue from 24 donors with incidental Lewy body disease, PD, PD with dementia (PDD), DLB and age-matched controls. The load and distribution of α-synuclein pathology and tyrosine hydroxylase (TH) cells were studied throughout the Insular subregions. The selective involvement of von Economo neurons (VENs) in the anterior Insula and astroglia was assessed in all groups. Results: A decreasing gradient of α-synuclein pathology load from the anterior periallocortical Agranular towards the intermediate dysgranular and posterior isocortical granular Insular subregions was found. Few VENs revealed α-synuclein inclusions while astroglial synucleinopathy was a predominant feature in PDD and DLB. TH neurons were predominant in the Agranular and dysgranular subregions but did not reveal α-synuclein inclusions or significant reduction in density in patient groups. Conclusions: Our study highlights the vulnerability of the anterior Agranular Insula to α-synuclein pathology in PD, PDD and DLB. Whereas VENs and astrocytes were affected in advanced disease stages, Insular TH neurons were spared. Owing to the anterior Insula's affective, cognitive and autonomic functions, its greater vulnerability to pathology indicates a potential contribution to nonmotor deficits in PD and DLB.

  • Insular cortex sub-region-dependent distribution pattern of α-synuclein immunoreactivity in Parkinson’s disease and dementia with Lewy bodies
    2017
    Co-Authors: Yasmine Y. Fathy, F.j.j. De Jong, A.m.w. Van Dam, Annemieke J.m. Rozemuller, W. D. J. Van De Berg
    Abstract:

    The Insular cortex is a heterogeneous and widely connected brain region. It plays a role in autonomic, cognitive, emotional and somatosensory functions. Its complex and unique cytoarchitecture includes a periallocortical Agranular, pro-isocortical dysgranular, and isocortical granular sub-regions. In Parkinson9s disease (PD), the Insula shows α-synuclein inclusions in advanced stages of the disease and its atrophy correlates with cognitive deficits. However, little is known regarding its regional neuropathological characteristics and vulnerability in Lewy body diseases. The aim of this study is to assess the distribution pattern of α-synuclein pathology in the Insular sub-regions and the selective vulnerability of its different cell types in PD and dementia with Lewy bodies (DLB). Human post-mortem Insular tissues from 10 donors with incidental Lewy body disease (iLBD), PD, DLB, and age-matched controls were immunostained for α-synuclein and glial fibrillary acid protein (GFAP). Results showed that a decreasing gradient of α-synuclein pathology was present from Agranular to granular sub-regions in iLBD, PD and PD with dementia (PDD) donors. The Agranular Insula was heavily inflicted, revealing various α-synuclein immunoreactive morphological structures, predominantly Lewy neurites (LNs), and astroglial synucleinopathy. While dysgranular and granular sub-regions showed a decreasing gradient of inclusions and more Lewy bodies (LBs) in deeper layers. In DLB, this gradient was less pronounced and severe pathology was observed in the granular Insula compared to PDD and regardless of disease stage. Protoplasmic astrocytes showed α-synuclein inclusions and severe degenerative changes increasing with disease severity. While few von Economo neurons (VENs) in the fronto-Insular region revealed inclusions, particularly in PDD patients. Our study reports novel findings on the differential involvement of the Insular sub-regions in PD and particular involvement of the Agranular sub-region, VENs and astrocytes. Thus, the differential cellular architecture of the Insular sub-regions portrays the topographic variation and vulnerability to α-synuclein pathology in Lewy body diseases.