The anatomical connections of the macaque monkey orbitofrontal cortex. A review

The orbitofrontal cortex (OfC) is a heterogeneous prefrontal sector selectively connected with a wide constellation of other prefrontal, limbic, sensory and premotor areas. Among the limbic cortical connections, the ones with the bippocampus and parabippocampal cortex are particularly salient. Sensory cortices connected with the OfC include areas involved in olfactory, gustatory, somatosensory, auditory and visual processing. Subcortical structures with prominent OfC connections include the amygdala, numerous thalamic nuclei, the striatum, hypothalamus, periaqueductal gray matter, and biochemically specific cell groups in the basal forebrain and brainstem. Architectonic and connectional evidence supports parcellation of the OfC. The rostrally placed isocortical sector is mainly connected with isocortical areas, including sensory areas of the auditory, somatic and visual modalities, whereas the caudal non-isocortical sector is principally connected with non-isocortical areas, and, in the sensory domain, with olfactory and gustatory areas. The connections of the isocortical and non- isocortical orbital sectors with the amygdala, thalamus, striatum, hypotbalamus and periaqueductal gray matter are also specific. The medial sector of the OfC is selectively connected with the bippocampus, posterior parabippocampal cortex, posterior cingulate and retrosplenial areas, and area prostriata, while the lateral orbitofrontal sector is the most heavily connected with sensory areas of the gustatory, somatic and visual modalities, with premotor regions, and with the amygdala.

条件反射性免疫抑制及其脑机制的c-fos研究

To explore the neural mechanisms underlying conditioned immunomodulation, this study employed the classical taste aversion (CTA) behavioral paradigm to establish the conditioned humoral and cellular immunosuppression (CIS) in Wistar rats, by paring saccharin (CS) with intraperitoneal (i.p.) injection of an immunosuppressive drug cyclophophamide (UCS). C-fos immunohistochemistry method was used to observe the changes of the neuronal activities in the rat brain during the acquisition, expression and extinction of the conditioned immunosuppression (CIS). The followings are the main results: 1. Five days after one trial of CS-UCS paring, reexposure to CS alone significantly decreased the level of the anti-ovalbumin (OVA) IgG in the peripheral serum. Two trials of CS-UCS paring and three reexposures to CS not only resulted in further suppression of the primary immune response, but also reduced the numbers of peripheral lymphocytes and white blood cells. This finding indicates that CS can induce suppression of the immune function, and the magnitude of the effects is dependent on the intensity of training. 2. On day 5 following two trials of CS-UCS pairing, CS suppressed the spleen lymphocytes responsiveness to mitogens ConA, PHA and PWM, and decreased the numbers of peripheral lymphocytes and white blood cells. On day 15, only PHA induced lymphocyte proliferation was suppressed by CS. On day 30, presentation of CS did not have any effect on these immune parameters. These results suggest that the conditioned suppression of the cellular immune function can retain 5-15 days, and extinct after 30 days. 3. CTA was easily induced by one or two CS-UCS parings, and remained robust even after 30 days. These data demonstrate that CIS can be dissociated from CTA, and they may be mediated by different neural mechanisms. 4. Immunohistochemistry assays revealed a broad pattern of c-fos expression throughout the rat brain following the CS-UCS pairing and reexposure to CS, suggesting that many brain regions are involved in CIS. Some brain areas including the solitary tract nucleus (Sol), lateral parabrachial nucleus (LPB) and insular cortex (IC), showed high level c-fos expressions in response to both CS and UCS, suggesting that they may be involved in the transmission and integration of the CS and UCS signals in the brain. There were dense c-FOS positive neurons in the paraverntricular nucleus (PVN) and supraoptic nucleus (SO) of hypothalamus, subfornical organ (SFO) and area postrema (AP) etc. after two trials of CS-UCS paring and after the reexposure to CS 5 days later, but not in the first training and after the extinction of CIS (30 days later). The results reflect that these nuclei may have an important role in CIS expression, and may also response to the immunosuppression of UCS. The conditioned training and reexposure to CS 5 days later induced high level c-fos expression in the cingulate cortex (Cg), central amygdaloid nucleus (Ce), intermediate part of lateral septal nucleus (LSI) and ventrolateral parabrachial nucleus (VLPB) etc. But c-fos induction was not apparent when presenting CS 30 days later. These brain regions are mainly involved in CIS, and may be critical structures in the acquisition and expression of CIS. Some brain regions, including the frontal cortex (Fr), ventral orbital cortex (VO), IC, perirhinal cortex (PRh), LPB and the medial part of solitary nucleus (SolM), showed robust c-FOS expression following the conditioning training and reexposure to CS both on day 5 and day 30, suggesting that they are critically involved in CTA.

The contributions of the amygdala, orbital frontal cortex and hippocampal formation to primate social cognition

Deficits in social cognition are prominent symptoms of many human psychiatric disorders, but the origin of such deficits remains largely unknown. To further current knowledge regarding the neural network mediating social cognition, the present research program investigated the individual contributions of two temporal lobe structures, the amygdala and hippocampal formation, and one frontal lobe region, the orbital frontal cortex (Areas 11 and 13), to primate social cognition. Based on previous research, we hypothesized that the amygdala, hippocampal formation and orbital frontal cortex contribute significantly to the formation of new social relationships, but less to the maintenance of familiar ones. ^ Thirty-six male rhesus macaques (Macaca mulatta) served as subjects, and were divided into four experimental groups: Neurotoxic amygdala lesion (A-ibo, n = 9), neurotoxic or aspiration orbital frontal cortex lesion (O, n = 9), neurotoxic hippocampal formation lesion (H-ibo, n = 9) or sham-operated control (C, n = 9). Six social groups (tetrads) were created, each containing one member from each experimental group. The effect of lesion on established social relationships was assessed during pre- and post-surgical unrestrained social interactions, whereas the effect of lesion on the formation of new relationships was assessed during an additional phase of post-surgical testing with shuffled tetrad membership. Results indicated that these three neural structures each contribute significantly to both the formation and maintenance of social relationships. Furthermore, the amygdala appears to primarily mediate normal responses to threatening social signals, whereas the orbital frontal cortex plays a more global role in social cognition by mediating responses to both threatening and affiliative social signals. By contrast, the hippocampal formation seems to contribute to social cognition indirectly by providing access to previous experience during social judgments. ^ These conclusions were further investigated with three experiments that measured behavioral and physiological (stress hormone) reactivity to threatening stimuli, and three additional experiments that measured subjects' ability to flexibly alter behavioral responses depending on the incentive value of a food reinforcer. Data from these six experiments further confirmed and strengthened the three conclusions originating from the social behavior experiments and, when combined with the current literature, helped to formulate a simple, but testable, theoretical model of primate social cognition. ^

Effects of early and late lesion of orbital frontal cortex on visual processing of faces in rhesus macaques (Macaca mulatta)

Many mental disorders disrupt social skills, yet few studies have examined how the brain processes social information. Functional neuroimaging, neuroconnectivity and electrophysiological studies suggest that orbital frontal cortex plays important roles in social cognition, including the analysis of information from faces, which are important cues in social interactions. Studies in humans and non-human primates show that damage to orbital frontal cortex produces social behavior impairments, including abnormal aggression, but these studies have failed to determine whether damage to this area impairs face processing. In addition, it is not known whether damage early in life is more detrimental than damage in adulthood. This study examined whether orbital frontal cortex is necessary for the discrimination of face identity and facial expressions, and for appropriate behavioral responses to aggressive (threatening) facial expressions. Rhesus monkeys (Macaca mulatta) received selective lesions of orbital frontal cortex as newborns or adults. As adults, these animals were compared with sham-operated controls on their ability to discriminate between faces of individual monkeys and between different facial expressions of emotion. A passive visual paired-comparison task with standardized rhesus monkey face stimuli was designed and used to assess discrimination. In addition, looking behavior toward aggressive expressions was assessed and compared with that of normal control animals. The results showed that lesion of orbital frontal cortex (1) may impair discrimination between faces of individual monkeys, (2) does not impair facial expression discrimination, and (3) changes the amount of time spent looking at aggressive (threatening) facial expressions depending on the context. The effects of early and late lesions did not differ. Thus, orbital frontal cortex appears to be part of the neural circuitry for recognizing individuals and for modulating the response to aggression in faces, and the plasticity of the immature brain does not allow for recovery of these functions when the damage occurs early in life. This study opens new avenues for the assessment of rhesus monkey face processing and the neural basis of social cognition, and allows a better understanding of the nature of the neuropathology in patients with mental disorders that disrupt social behavior, such as autism. ^

Updating existing emotional memories involves the frontopolar/orbitofrontal cortex in ways that acquiring new emotional memories does not

In life, we must often learn new associations to people, places, or things we already know. The current fMRI study investigated the neural mechanisms underlying emotional memory updating. Nineteen participants first viewed negative and neutral pictures and learned associations between those pictures and other neutral stimuli, such as neutral objects and encoding tasks. This initial learning phase was followed by a memory updating phase, during which participants learned picture-location associations for old pictures (i.e., pictures previously associated with other neutral stimuli) and new pictures (i.e., pictures not seen in the first phase). There was greater frontopolar/orbito-frontal (OFC) activity when people learned picture–location associations for old negative pictures than for new negative pictures, but frontopolar OFC activity did not significantly differ during learning locations of old versus new neutral pictures. In addition, frontopolar activity was more negatively correlated with the amygdala when participants learned picture–location associations for old negative pictures than for new negative or old neutral pictures. Past studies revealed that the frontopolar OFC allows for updating the affective values of stimuli in reversal learning or extinction of conditioning [e.g., Izquierdo, A., & Murray, E. A. Opposing effects of amygdala and orbital PFC lesions on the extinction of instrumental responding in macaque monkeys. European Journal of Neuroscience, 22, 2341–2346, 2005]; our findings suggest that it plays a more general role in updating associations to emotional stimuli.

Pyramidal cells in prefrontal cortex: comparative observations reveal unparalleled specializations in neuronal structure among primate species

The most ubiquitous neuron in the cerebral cortex, the pyramidal cell, is characterized by markedly different dendritic structure among different cortical areas. The complex pyramidal cell phenotype in granular prefrontal cortex (gPFC) of higher primates endows specific biophysical properties and patterns of connectivity, which differ from those in other cortical regions. However, within the gPFC, data have been sampled from only a select few cortical areas. The gPFC of species such as human and macaque monkey includes more than 10 cortical areas. It remains unknown as to what degree pyramidal cell structure may vary among these cortical areas. Here we undertook a survey of pyramidal cells in the dorsolateral, medial, and orbital gPFC of cercopithecid primates. We found marked heterogeneity in pyramidal cell structure within and between these regions. Moreover, trends for gradients in neuronal complexity varied among species. As the structure of neurons determines their computational abilities, memory storage capacity and connectivity, we propose that these specializations in the pyramidal cell phenotype are an important determinant of species-specific executive cortical functions in primates.

Reduced gray matter volume in ventral prefrontal cortex but not amygdala in bipolar disorder:significant effects of gender and trait anxiety

Neuroimaging studies in bipolar disorder report gray matter volume (GMV) abnormalities in neural regions implicated in emotion regulation. This includes a reduction in ventral/orbital medial prefrontal cortex (OMPFC) GMV and, inconsistently, increases in amygdala GMV. We aimed to examine OMPFC and amygdala GMV in bipolar disorder type 1 patients (BPI) versus healthy control participants (HC), and the potential confounding effects of gender, clinical and illness history variables and psychotropic medication upon any group differences that were demonstrated in OMPFC and amygdala GMV. Images were acquired from 27 BPI (17 euthymic, 10 depressed) and 28 age- and gender-matched HC in a 3T Siemens scanner. Data were analyzed with SPM5 using voxel-based morphometry (VBM) to assess main effects of diagnostic group and gender upon whole brain (WB) GMV. Post-hoc analyses were subsequently performed using SPSS to examine the extent to which clinical and illness history variables and psychotropic medication contributed to GMV abnormalities in BPI in a priori and non-a priori regions has demonstrated by the above VBM analyses. BPI showed reduced GMV in bilateral posteromedial rectal gyrus (PMRG), but no abnormalities in amygdala GMV. BPI also showed reduced GMV in two non-a priori regions: left parahippocampal gyrus and left putamen. For left PMRG GMV, there was a significant group by gender by trait anxiety interaction. GMV was significantly reduced in male low-trait anxiety BPI versus male low-trait anxiety HC, and in high- versus low-trait anxiety male BPI. Our results show that in BPI there were significant effects of gender and trait-anxiety, with male BPI and those high in trait-anxiety showing reduced left PMRG GMV. PMRG is part of medial prefrontal network implicated in visceromotor and emotion regulation.

Time-Dependent Density Functional Molecular Orbital and Excited State Calculations on Bis(porphyrinyl)butadiynes in the Monocationic, Neutral, Monoanionic, and Dianionic Oxidation States

We report a theoretical study of the multiple oxidation states (1+, 0, 1−, and 2−) of a meso,meso-linked diporphyrin, namely bis[10,15,20-triphenylporphyrinatozinc(II)-5-yl]butadiyne (4), using Time-Dependent Density Functional Theory (TDDFT). The origin of electronic transitions of singlet excited states is discussed in comparison to experimental spectra for the corresponding oxidation states of the close analogue bis{10,15,20-tris[3‘,5‘-di-tert-butylphenyl]porphyrinatozinc(II)-5-yl}butadiyne (3). The latter were measured in previous work under in situ spectroelectrochemical conditions. Excitation energies and orbital compositions of the excited states were obtained for these large delocalized aromatic radicals, which are unique examples of organic mixed-valence systems. The radical cations and anions of butadiyne-bridged diporphyrins such as 3 display characteristic electronic absorption bands in the near-IR region, which have been successfully predicted with use of these computational methods. The radicals are clearly of the “fully delocalized” or Class III type. The key spectral features of the neutral and dianionic states were also reproduced, although due to the large size of these molecules, quantitative agreement of energies with observations is not as good in the blue end of the visible region. The TDDFT calculations are largely in accord with a previous empirical model for the spectra, which was based simplistically on one-electron transitions among the eight key frontier orbitals of the C4 (1,4-butadiyne) linked diporphyrins.

Super-orbital re-entry in Australia : laboratory measurement, simulation and flight observation

There are large uncertainties in the aerothermodynamic modelling of super-orbital re-entry which impact the design of spacecraft thermal protection systems (TPS). Aspects of the thermal environment of super-orbital re-entry flows can be simulated in the laboratory using arc- and plasma jet facilities and these devices are regularly used for TPS certification work [5]. Another laboratory device which is capable of simulating certain critical features of both the aero and thermal environment of super-orbital re-entry is the expansion tube, and three such facilities have been operating at the University of Queensland in recent years[10]. Despite some success, wind tunnel tests do not achieve full simulation, however, a virtually complete physical simulation of particular re-entry conditions can be obtained from dedicated flight testing, and the Apollo era FIRE II flight experiment [2] is the premier example which still forms an important benchmark for modern simulations. Dedicated super-orbital flight testing is generally considered too expensive today, and there is a reluctance to incorporate substantial instrumentation for aerothermal diagnostics into existing missions since it may compromise primary mission objectives. An alternative approach to on-board flight measurements, with demonstrated success particularly in the ‘Stardust’ sample return mission, is remote observation of spectral emissions from the capsule and shock layer [8]. JAXA’s ‘Hayabusa’ sample return capsule provides a recent super-orbital reentry example through which we illustrate contributions in three areas: (1) physical simulation of super-orbital re-entry conditions in the laboratory; (2) computational simulation of such flows; and (3) remote acquisition of optical emissions from a super-orbital re entry event.

Image-based visual servoing for the super-orbital re-entry of Hayabusa spacecraft

This paper presents an image-based visual servoing system that was used to track the atmospheric Earth re-entry of Hayabusa. The primary aim of this ground based tracking platform was to record the emission spectrum radiating from the superheated gas of the shock layer and the surface of the heat shield during re-entry. To the author's knowledge, this is the first time that a visual servoing system has successfully tracked a super-orbital re-entry of a spacecraft and recorded its pectral signature. Furthermore, we improved the system by including a simplified dynamic model for feed-forward control and demonstrate improved tracking performance on the International Space Station (ISS). We present comparisons between simulation and experimental results on different target trajectories including tracking results from Hayabusa and ISS. The required performance for tracking both spacecraft is demanding when combined with a narrow field of view (FOV). We also briefly discuss the preliminary results obtained from the spectroscopy of the Hayabusa's heat shield during re-entry.

Benign Epilepsy with Centro-temporal Spikes: Spike Triggered fMRI Shows Somato-sensory Cortex Activity

Summary:  Objective: We performed spike triggered functional MRI (fMRI) in a 12 year old girl with Benign Epilepsy with Centro-temporal Spikes (BECTS) and left-sided spikes. Our aim was to demonstrate the cerebral origin of her interictal spikes. Methods: EEG was recorded within the 3 Tesla MRI. Whole brain fMRI images were acquired, beginning 2–3 seconds after spikes. Baseline fMRI images were acquired when there were no spikes for 20 seconds. Image sets were compared with the Student's t-test. Results: Ten spike and 20 baseline brain volumes were analysed. Focal activiation was seen in the inferior left sensorimotor cortex near the face area. The anterior cingulate was more active during baseline than spikes. Conclusions: Left sided epileptiform activity in this patient with BECTS is associated with fMRI activation in the left face region of the somatosensory cortex, which would be consistent with the facial sensorimotor involvement in BECT seizures. The presence of BOLD signal change in other regions raises the possibility that the scalp recorded field of this patient with BECTs may reflect electrical change in more than one brain region.

Protein markers for Alzheimer disease in the frontal cortex and cerebellum

Objective: To compare proteins related to Alzheimer disease ( AD) in the frontal cortex and cerebellum of subjects with early-onset AD (EOAD) with or without presenilin 1 (PS1) mutations with sporadic late-onset AD ( LOAD) and nondemented control subjects. Methods: Immunohistochemistry, immunoblot analysis, and ELISA were used to detect and assess protein levels in brain. Results: In EOAD and to a lesser extent in LOAD, there was increased amyloid beta (Abeta) deposition (by immunohistochemistry), increased soluble Abeta (by immunoblot analysis), and specific increases in Abeta(40) and Abeta(42) ( by ELISA) in the frontal cortex and, in some cases, in the cerebellum. Surprisingly, immunoblot analysis revealed reduced levels of PS1 in many of the subjects with EOAD with or without PS1 mutations. In those PS1 mutation-bearing subjects with the highest Abeta, PS1 was barely, if at all, detectable. This decrease in PS1 was specific and not attributable solely to neuronal loss because amyloid precursor protein (APP) and the PS1-interacting protein beta-catenin levels were unchanged. Conclusions: This study shows that in the frontal cortex and cerebellum from Alzheimer disease patients harboring certain presenilin 1 mutations, high levels of amyloid beta are associated with low levels of presenilin 1. The study provides the premise for further investigation of mechanisms underlying the downregulation of presenilin 1, which may have considerable pathogenic and therapeutic relevance.

Cerebral cortex activation mapping upon electrical muscle stimulation by 32-channel time-domain functional near-infrared spectroscopy

The application of different EMS current thresholds on muscle activates not only the muscle but also peripheral sensory axons that send proprioceptive and pain signals to the cerebral cortex. A 32-channel time-domain fNIRS instrument was employed to map regional cortical activities under varied EMS current intensities applied on the right wrist extensor muscle. Eight healthy volunteers underwent four EMS at different current thresholds based on their individual maximal tolerated intensity (MTI), i.e., 10 % < 50 % < 100 % < over 100 % MTI. Time courses of the absolute oxygenated and deoxygenated hemoglobin concentrations primarily over the bilateral sensorimotor cortical (SMC) regions were extrapolated, and cortical activation maps were determined by general linear model using the NIRS-SPM software. The stimulation-induced wrist extension paradigm significantly increased activation of the contralateral SMC region according to the EMS intensities, while the ipsilateral SMC region showed no significant changes. This could be due in part to a nociceptive response to the higher EMS current intensities and result also from increased sensorimotor integration in these cortical regions.