WorldWideScience

Sample records for paralyzed monkey brain-controlled

  1. Toward the restoration of hand use to a paralyzed monkey: brain-controlled functional electrical stimulation of forearm muscles.

    Directory of Open Access Journals (Sweden)

    Eric A Pohlmeyer

    2009-06-01

    Full Text Available Loss of hand use is considered by many spinal cord injury survivors to be the most devastating consequence of their injury. Functional electrical stimulation (FES of forearm and hand muscles has been used to provide basic, voluntary hand grasp to hundreds of human patients. Current approaches typically grade pre-programmed patterns of muscle activation using simple control signals, such as those derived from residual movement or muscle activity. However, the use of such fixed stimulation patterns limits hand function to the few tasks programmed into the controller. In contrast, we are developing a system that uses neural signals recorded from a multi-electrode array implanted in the motor cortex; this system has the potential to provide independent control of multiple muscles over a broad range of functional tasks. Two monkeys were able to use this cortically controlled FES system to control the contraction of four forearm muscles despite temporary limb paralysis. The amount of wrist force the monkeys were able to produce in a one-dimensional force tracking task was significantly increased. Furthermore, the monkeys were able to control the magnitude and time course of the force with sufficient accuracy to track visually displayed force targets at speeds reduced by only one-third to one-half of normal. Although these results were achieved by controlling only four muscles, there is no fundamental reason why the same methods could not be scaled up to control a larger number of muscles. We believe these results provide an important proof of concept that brain-controlled FES prostheses could ultimately be of great benefit to paralyzed patients with injuries in the mid-cervical spinal cord.

  2. Brain-Machine Interface Enables Bimanual Arm Movements in Monkeys

    Science.gov (United States)

    Ifft, Peter J.; Shokur, Solaiman; Li, Zheng; Lebedev, Mikhail A.; Nicolelis, Miguel A. L.

    2014-01-01

    Brain-machine interfaces (BMIs) are artificial systems that aim to restore sensation and movement to severely paralyzed patients. However, previous BMIs enabled only single arm functionality, and control of bimanual movements was a major challenge. Here, we developed and tested a bimanual BMI that enabled rhesus monkeys to control two avatar arms simultaneously. The bimanual BMI was based on the extracellular activity of 374–497 neurons recorded from several frontal and parietal cortical areas of both cerebral hemispheres. Cortical activity was transformed into movements of the two arms with a decoding algorithm called a 5th order unscented Kalman filter (UKF). The UKF is well-suited for BMI decoding because it accounts for both characteristics of reaching movements and their representation by cortical neurons. The UKF was trained either during a manual task performed with two joysticks or by having the monkeys passively observe the movements of avatar arms. Most cortical neurons changed their modulation patterns when both arms were engaged simultaneously. Representing the two arms jointly in a single UKF decoder resulted in improved decoding performance compared with using separate decoders for each arm. As the animals’ performance in bimanual BMI control improved over time, we observed widespread plasticity in frontal and parietal cortical areas. Neuronal representation of the avatar and reach targets was enhanced with learning, whereas pairwise correlations between neurons initially increased and then decreased. These results suggest that cortical networks may assimilate the two avatar arms through BMI control. PMID:24197735

  3. Connections that Count: Brain-Computer Interface Enables the Profoundly Paralyzed to Communicate

    Science.gov (United States)

    ... Home Current Issue Past Issues Connections that Count: Brain-Computer Interface Enables the Profoundly Paralyzed to Communicate Past Issues / ... of this page please turn Javascript on. A brain-computer interface (BCI) system This brain-computer interface (BCI) system ...

  4. Invasive brain-machine interfaces: a survey of paralyzed patients’ attitudes, knowledge and methods of information retrieval

    Science.gov (United States)

    Lahr, Jacob; Schwartz, Christina; Heimbach, Bernhard; Aertsen, Ad; Rickert, Jörn; Ball, Tonio

    2015-08-01

    Objective. Brain-machine interfaces (BMI) are an emerging therapeutic option that can allow paralyzed patients to gain control over assistive technology devices (ATDs). BMI approaches can be broadly classified into invasive (based on intracranially implanted electrodes) and noninvasive (based on skin electrodes or extracorporeal sensors). Invasive BMIs have a favorable signal-to-noise ratio, and thus allow for the extraction of more information than noninvasive BMIs, but they are also associated with the risks related to neurosurgical device implantation. Current noninvasive BMI approaches are typically concerned, among other issues, with long setup times and/or intensive training. Recent studies have investigated the attitudes of paralyzed patients eligible for BMIs, particularly patients affected by amyotrophic lateral sclerosis (ALS). These studies indicate that paralyzed patients are indeed interested in BMIs. Little is known, however, about the degree of knowledge among paralyzed patients concerning BMI approaches or about how patients retrieve information on ATDs. Furthermore, it is not yet clear if paralyzed patients would accept intracranial implantation of BMI electrodes with the premise of decoding improvements, and what the attitudes of a broader range of patients with diseases such as stroke or spinal cord injury are towards this new kind of treatment. Approach. Using a questionnaire, we surveyed 131 paralyzed patients for their opinions on invasive BMIs and their attitude toward invasive BMI treatment options. Main results. The majority of the patients knew about and had a positive attitude toward invasive BMI approaches. The group of ALS patients was especially open to the concept of BMIs. The acceptance of invasive BMI technology depended on the improvements expected from the technology. Furthermore, the survey revealed that for paralyzed patients, the Internet is an important source of information on ATDs. Significance. Websites tailored to

  5. Nessi: An EEG-Controlled Web Browser for Severely Paralyzed Patients

    Directory of Open Access Journals (Sweden)

    Michael Bensch

    2007-01-01

    Full Text Available We have previously demonstrated that an EEG-controlled web browser based on self-regulation of slow cortical potentials (SCPs enables severely paralyzed patients to browse the internet independently of any voluntary muscle control. However, this system had several shortcomings, among them that patients could only browse within a limited number of web pages and had to select links from an alphabetical list, causing problems if the link names were identical or if they were unknown to the user (as in graphical links. Here we describe a new EEG-controlled web browser, called Nessi, which overcomes these shortcomings. In Nessi, the open source browser, Mozilla, was extended by graphical in-place markers, whereby different brain responses correspond to different frame colors placed around selectable items, enabling the user to select any link on a web page. Besides links, other interactive elements are accessible to the user, such as e-mail and virtual keyboards, opening up a wide range of hypertext-based applications.

  6. Monkey brain damage from radiation in the therapeutic range

    International Nuclear Information System (INIS)

    Nakagaki, H.; Brunhart, G.; Kemper, T.L.; Caveness, W.F.

    1976-01-01

    Twelve Macaca mulatta monkeys received 200 rads of supervoltage radiation to the whole brain per day, 5 days a week. The course in four monkeys was 4 weeks for a total dose of 4000 rads; in four monkeys, 6 weeks for 6000 rads; and in four monkeys, 8 weeks for 8000 rads. Four unirradiated monkeys served as controls. One from each group, sacrificed at 6 and 12 months from start of irradiation, is reported here. The results from 4000 rads were negligible; those from 8000 rads, profound, with gross brain destruction. The results from 6000 rads, within the therapeutic range, included at 6 months punctate necrotic lesions, 1 mm or less, widely scattered but with a predilection for the forebrain white matter. The reaction to these lesions ranged from an early macrophage response to calcification. Some were accompanied by focal edema. There were occasional examples of vascular endothelial proliferation. In addition, there were patches of dilated capillaries or telangiectasia. Twelve months after 6000 rads there were a few mineralized lesions and innumerable minute deposits of calcium and iron. A more active process was suggested by widely disseminated areas of telangiectasia, 6 to 12 mm in extent. The clinical course from this exposure included papilledema from the third to the sixth month and depressed visual evoked response accompanied by delta activity in the electroencephalogram from the sixth to the twelfth month

  7. Mutant alpha-synuclein causes age-dependent neuropathology in monkey brain.

    Science.gov (United States)

    Yang, Weili; Wang, Guohao; Wang, Chuan-En; Guo, Xiangyu; Yin, Peng; Gao, Jinquan; Tu, Zhuchi; Wang, Zhengbo; Wu, Jing; Hu, Xintian; Li, Shihua; Li, Xiao-Jiang

    2015-05-27

    Parkinson's disease (PD) is an age-dependent neurodegenerative disease that often occurs in those over age 60. Although rodents and small animals have been used widely to model PD and investigate its pathology, their short life span makes it difficult to assess the aging-related pathology that is likely to occur in PD patient brains. Here, we used brain tissues from rhesus monkeys at 2-3, 7-8, and >15 years of age to examine the expression of Parkin, PINK1, and α-synuclein, which are known to cause PD via loss- or gain-of-function mechanisms. We found that α-synuclein is increased in the older monkey brains, whereas Parkin and PINK1 are decreased or remain unchanged. Because of the gain of toxicity of α-synuclein, we performed stereotaxic injection of lentiviral vectors expressing mutant α-synuclein (A53T) into the substantia nigra of monkeys and found that aging also increases the accumulation of A53T in neurites and its associated neuropathology. A53T also causes more extensive reactive astrocytes and axonal degeneration in monkey brain than in mouse brain. Using monkey brain tissues, we found that A53T interacts with neurofascin, an adhesion molecule involved in axon subcellular targeting and neurite outgrowth. Aged monkey brain tissues show an increased interaction of neurofascin with A53T. Overexpression of A53T causes neuritic toxicity in cultured neuronal cells, which can be attenuated by transfected neurofascin. These findings from nonhuman primate brains reveal age-dependent pathological and molecular changes that could contribute to the age-dependent neuropathology in PD. Copyright © 2015 the authors 0270-6474/15/358345-14$15.00/0.

  8. Short parietal lobe connections of the human and monkey brain

    DEFF Research Database (Denmark)

    Catani, Marco; Robertsson, Naianna; Beyh, Ahmad

    2017-01-01

    projections were reconstructed for both species and results compared to identify similarities or differences in tract anatomy (i.e., trajectories and cortical projections). In addition, post-mortem dissections were performed in a human brain. The largest tract identified in both human and monkey brains...... and angular gyri of the inferior parietal lobule in humans but only to the supramarginal gyrus in the monkey brain. The third tract connects the postcentral gyrus to the anterior region of the superior parietal lobule and is more prominent in monkeys compared to humans. Finally, short U-shaped fibres...... and monkeys with some differences for those areas that have cytoarchitectonically distinct features in humans. The overall pattern of intraparietal connectivity supports the special role of the inferior parietal lobule in cognitive functions characteristic of humans....

  9. Neuromyelitis optica immunoglobulin G in Chinese patients detected by immunofluorescence assay on a monkey brain substrate.

    Science.gov (United States)

    Long, Youming; Hu, Xueqiang; Peng, Fuhua; Lu, Zhengqi; Wang, Yuge; Yang, Yu; Qiu, Wei

    2012-01-01

    Serum neuromyelitis optica immunoglobulin G (NMO-IgG) is used as a biomarker to differentiate between neuromyelitis optica (NMO) and multiple sclerosis (MS). However, the original assay is expensive and complex and shows low sensitivity. Here, we investigated the potential of NMO-IgG detection using an indirect immunofluorescence (IIF) assay on monkey brains. NMO-IgG seroprevalence was determined in 168 samples by an IIF assay on a monkey brain substrate. The data were compared with those from a standard mouse brain IIF assay using McNemar and kappa tests. Thirty-one of 50 (62%) NMO patients, 7 of 18 (38.9%) longitudinally extensive transverse myelitis patients, 6 of 57 (10.5%) MS patients, and 5 of 10 (50%) optic neuritis patients were seropositive for NMO-IgG. None of the acute partial transverse myelitis patients (n = 3) or healthy controls (n = 20) was positive. Thus, the sensitivity of the test was 62% for the patients with clinically definite NMO. The specificity was 89.5%, considering the 57 MS patients as the control group. The modified IIF assay on monkey brains and the standard IIF assay based on mouse brains were not significantly different (McNemar test; p = 1.000). The two assays were concordant in 39 seropositive samples and 100 seronegative samples (kappa test; kappa = 0.592, p monkey brain assay was no better than the standard mouse brain IIF assay, we affirmed that NMO-IgG is a sensitive and specific biomarker to differentiate between NMO and MS. Copyright © 2011 S. Karger AG, Basel.

  10. Wireless Cortical Brain-Machine Interface for Whole-Body Navigation in Primates

    Science.gov (United States)

    Rajangam, Sankaranarayani; Tseng, Po-He; Yin, Allen; Lehew, Gary; Schwarz, David; Lebedev, Mikhail A.; Nicolelis, Miguel A. L.

    2016-03-01

    Several groups have developed brain-machine-interfaces (BMIs) that allow primates to use cortical activity to control artificial limbs. Yet, it remains unknown whether cortical ensembles could represent the kinematics of whole-body navigation and be used to operate a BMI that moves a wheelchair continuously in space. Here we show that rhesus monkeys can learn to navigate a robotic wheelchair, using their cortical activity as the main control signal. Two monkeys were chronically implanted with multichannel microelectrode arrays that allowed wireless recordings from ensembles of premotor and sensorimotor cortical neurons. Initially, while monkeys remained seated in the robotic wheelchair, passive navigation was employed to train a linear decoder to extract 2D wheelchair kinematics from cortical activity. Next, monkeys employed the wireless BMI to translate their cortical activity into the robotic wheelchair’s translational and rotational velocities. Over time, monkeys improved their ability to navigate the wheelchair toward the location of a grape reward. The navigation was enacted by populations of cortical neurons tuned to whole-body displacement. During practice with the apparatus, we also noticed the presence of a cortical representation of the distance to reward location. These results demonstrate that intracranial BMIs could restore whole-body mobility to severely paralyzed patients in the future.

  11. A brain MRI atlas of the common squirrel monkey, Saimiri sciureus

    Science.gov (United States)

    Gao, Yurui; Schilling, Kurt G.; Khare, Shweta P.; Panda, Swetasudha; Choe, Ann S.; Stepniewska, Iwona; Li, Xia; Ding, Zhoahua; Anderson, Adam; Landman, Bennett A.

    2014-03-01

    The common squirrel monkey, Saimiri sciureus, is a New World monkey with functional and microstructural organization of central nervous system similar to that of humans. It is one of the most commonly used South American primates in biomedical research. Unlike its Old World macaque cousins, no digital atlases have described the organization of the squirrel monkey brain. Here, we present a multi-modal magnetic resonance imaging (MRI) atlas constructed from the brain of an adult female squirrel monkey. In vivo MRI acquisitions include high resolution T2 structural imaging and low resolution diffusion tensor imaging. Ex vivo MRI acquisitions include high resolution T2 structural imaging and high resolution diffusion tensor imaging. Cortical regions were manually annotated on the co-registered volumes based on published histological sections.

  12. Conditional associative learning examined in a paralyzed patient with amyotrophic lateral sclerosis using brain-computer interface technology

    Directory of Open Access Journals (Sweden)

    Birbaumer N

    2008-11-01

    Full Text Available Abstract Background Brain-computer interface methodology based on self-regulation of slow-cortical potentials (SCPs of the EEG (electroencephalogram was used to assess conditional associative learning in one severely paralyzed, late-stage ALS patient. After having been taught arbitrary stimulus relations, he was evaluated for formation of equivalence classes among the trained stimuli. Methods A monitor presented visual information in two targets. The method of teaching was matching to sample. Three types of stimuli were presented: signs (A, colored disks (B, and geometrical shapes (C. The sample was one type, and the choice was between two stimuli from another type. The patient used his SCP to steer a cursor to one of the targets. A smiley was presented as a reward when he hit the correct target. The patient was taught A-B and B-C (sample – comparison matching with three stimuli of each type. Tests for stimulus equivalence involved the untaught B-A, C-B, A-C, and C-A relations. An additional test was discrimination between all three stimuli of one equivalence class presented together versus three unrelated stimuli. The patient also had sessions with identity matching using the same stimuli. Results The patient showed high accuracy, close to 100%, on identity matching and could therefore discriminate the stimuli and control the cursor correctly. Acquisition of A-B matching took 11 sessions (of 70 trials each and had to be broken into simpler units before he could learn it. Acquisition of B-C matching took two sessions. The patient passed all equivalence class tests at 90% or higher. Conclusion The patient may have had a deficit in acquisition of the first conditional association of signs and colored disks. In contrast, the patient showed clear evidence that A-B and B-C training had resulted in formation of equivalence classes. The brain-computer interface technology combined with the matching to sample method is a useful way to assess various

  13. Conditional associative learning examined in a paralyzed patient with amyotrophic lateral sclerosis using brain-computer interface technology.

    Science.gov (United States)

    Iversen, Ih; Ghanayim, N; Kübler, A; Neumann, N; Birbaumer, N; Kaiser, J

    2008-11-24

    Brain-computer interface methodology based on self-regulation of slow-cortical potentials (SCPs) of the EEG (electroencephalogram) was used to assess conditional associative learning in one severely paralyzed, late-stage ALS patient. After having been taught arbitrary stimulus relations, he was evaluated for formation of equivalence classes among the trained stimuli. A monitor presented visual information in two targets. The method of teaching was matching to sample. Three types of stimuli were presented: signs (A), colored disks (B), and geometrical shapes (C). The sample was one type, and the choice was between two stimuli from another type. The patient used his SCP to steer a cursor to one of the targets. A smiley was presented as a reward when he hit the correct target. The patient was taught A-B and B-C (sample - comparison) matching with three stimuli of each type. Tests for stimulus equivalence involved the untaught B-A, C-B, A-C, and C-A relations. An additional test was discrimination between all three stimuli of one equivalence class presented together versus three unrelated stimuli. The patient also had sessions with identity matching using the same stimuli. The patient showed high accuracy, close to 100%, on identity matching and could therefore discriminate the stimuli and control the cursor correctly. Acquisition of A-B matching took 11 sessions (of 70 trials each) and had to be broken into simpler units before he could learn it. Acquisition of B-C matching took two sessions. The patient passed all equivalence class tests at 90% or higher. The patient may have had a deficit in acquisition of the first conditional association of signs and colored disks. In contrast, the patient showed clear evidence that A-B and B-C training had resulted in formation of equivalence classes. The brain-computer interface technology combined with the matching to sample method is a useful way to assess various cognitive abilities of severely paralyzed patients, who are

  14. Experiencing Brain-Computer Interface Control

    NARCIS (Netherlands)

    van de Laar, B.L.A.

    2016-01-01

    Brain-Computer Interfaces (BCIs) are systems that extract information from the user’s brain activity and employ it in some way in an interactive system. While historically BCIs were mainly catered towards paralyzed or otherwise physically handicapped users, the last couple of years applications with

  15. Effects of anesthesia upon 18F-FDG uptake in rhesus monkey brains

    International Nuclear Information System (INIS)

    Itoh, Takashi; Wakahara, Shunichi; Nakano, Takayuki; Suzuki, Kazutoshi; Kobayashi, Kaoru; Inoue, Osamu

    2005-01-01

    The kinetics of 18 F-fluorodeoxyglucose ( 18 F-FDG) in the monkey brain were monitored, and comparisons were made between the conscious state and when under ketamine and pentobarbital anesthesia. Rhesus monkeys were intravenously injected with 18 F-FDG and followed by 60 min of PET scanning. In the conscious state, the 18 F-FDG concentration reached a plateau 5 min after intravenous injection. Under ketamine anesthesia, the 18 F-FDG concentration gradually increased with time in all monitored regions. At 60 min after injection, the concentration in the striatum was about 3.2 times greater than that in the conscious state, and about 4.5 times greater in the cerebral cortex. Under pentobarbital anesthesia, the 18 F-FDG concentration in the occipital cortex was slightly lower. These findings demonstrate that 18 F-FDG concentration in the monkey brain is significantly affected by anesthesia. The results also imply the existence of a short-term regulation mechanism for hexokinase activity in intact monkey brain. (author)

  16. Speaking and cognitive distractions during EEG-based brain control of a virtual neuroprosthesis-arm

    OpenAIRE

    Foldes, Stephen T; Taylor, Dawn M

    2013-01-01

    Background Brain-computer interface (BCI) systems have been developed to provide paralyzed individuals the ability to command the movements of an assistive device using only their brain activity. BCI systems are typically tested in a controlled laboratory environment were the user is focused solely on the brain-control task. However, for practical use in everyday life people must be able to use their brain-controlled device while mentally engaged with the cognitive responsibilities of daily a...

  17. Computing Arm Movements with a Monkey Brainet.

    Science.gov (United States)

    Ramakrishnan, Arjun; Ifft, Peter J; Pais-Vieira, Miguel; Byun, Yoon Woo; Zhuang, Katie Z; Lebedev, Mikhail A; Nicolelis, Miguel A L

    2015-07-09

    Traditionally, brain-machine interfaces (BMIs) extract motor commands from a single brain to control the movements of artificial devices. Here, we introduce a Brainet that utilizes very-large-scale brain activity (VLSBA) from two (B2) or three (B3) nonhuman primates to engage in a common motor behaviour. A B2 generated 2D movements of an avatar arm where each monkey contributed equally to X and Y coordinates; or one monkey fully controlled the X-coordinate and the other controlled the Y-coordinate. A B3 produced arm movements in 3D space, while each monkey generated movements in 2D subspaces (X-Y, Y-Z, or X-Z). With long-term training we observed increased coordination of behavior, increased correlations in neuronal activity between different brains, and modifications to neuronal representation of the motor plan. Overall, performance of the Brainet improved owing to collective monkey behaviour. These results suggest that primate brains can be integrated into a Brainet, which self-adapts to achieve a common motor goal.

  18. Default Mode of Brain Function in Monkeys

    Science.gov (United States)

    Mantini, Dante; Gerits, Annelis; Nelissen, Koen; Durand, Jean-Baptiste; Joly, Olivier; Simone, Luciano; Sawamura, Hiromasa; Wardak, Claire; Orban, Guy A.; Buckner, Randy L.; Vanduffel, Wim

    2013-01-01

    Human neuroimaging has revealed a specific network of brain regions—the default-mode network (DMN)—that reduces its activity during goal-directed behavior. So far, evidence for a similar network in monkeys is mainly indirect, since, except for one positron emission tomography study, it is all based on functional connectivity analysis rather than activity increases during passive task states. Here, we tested whether a consistent DMN exists in monkeys using its defining property. We performed a meta-analysis of functional magnetic resonance imaging data collected in 10 awake monkeys to reveal areas in which activity consistently decreases when task demands shift from passive tasks to externally oriented processing. We observed task-related spatially specific deactivations across 15 experiments, implying in the monkey a functional equivalent of the human DMN. We revealed by resting-state connectivity that prefrontal and medial parietal regions, including areas 9/46d and 31, respectively, constitute the DMN core, being functionally connected to all other DMN areas. We also detected two distinct subsystems composed of DMN areas with stronger functional connections between each other. These clusters included areas 24/32, 8b, and TPOC and areas 23, v23, and PGm, respectively. Such a pattern of functional connectivity largely fits, but is not completely consistent with anatomical tract tracing data in monkeys. Also, analysis of afferent and efferent connections between DMN areas suggests a multisynaptic network structure. Like humans, monkeys increase activity during passive epochs in heteromodal and limbic association regions, suggesting that they also default to internal modes of processing when not actively interacting with the environment. PMID:21900574

  19. Motor unit activation order during electrically evoked contractions of paralyzed or partially paralyzed muscles

    NARCIS (Netherlands)

    Thomas, CK; Nelson, G; Than, L; Zijdewind, Inge

    The activation order of motor units during electrically evoked contractions of paralyzed or partially paralyzed thenar muscles was determined in seven subjects with chronic cervical spinal cord injury. The median nerve was stimulated percutaneously with pulses of graded intensity to produce

  20. The Desire for Amputation or Paralyzation: Evidence for Structural Brain Anomalies in Body Integrity Identity Disorder (BIID).

    Science.gov (United States)

    Blom, Rianne M; van Wingen, Guido A; van der Wal, Sija J; Luigjes, Judy; van Dijk, Milenna T; Scholte, H Steven; Denys, Damiaan

    2016-01-01

    Body Integrity Identity Disorder (BIID) is a condition in which individuals perceive a mismatch between their internal body scheme and physical body shape, resulting in an absolute desire to be either amputated or paralyzed. The condition is hypothesized to be of congenital nature, but evidence for a neuro-anatomical basis is sparse. We collected T1-weighted structural magnetic resonance imaging scans on a 3T scanner in eight individuals with BIID and 24 matched healthy controls, and analyzed the data using voxel-based morphometry. The results showed reduced grey matter volume in the left dorsal and ventral premotor cortices and larger grey matter volume in the cerebellum (lobule VIIa) in individuals with BIID compared to controls. The premotor cortex and cerebellum are thought to be crucial for the experience of body-ownership and the integration of multisensory information. Our results suggest that BIID is associated with structural brain anomalies and might result from a dysfunction in the integration of multisensory information, leading to the feeling of disunity between the mental and physical body shape.

  1. N-isopropyl-[123I]p-iodoamphetamine: single-pass brain uptake and washout; binding to brain synaptosomes; and localization in dog and monkey brain

    International Nuclear Information System (INIS)

    Winchell, H.S.; Horst, W.D.; Braun, L.; Oldendorf, W.H.; Hattner, R.; Parker, H.

    1980-01-01

    The kinetics of N-isopropyl-p-[ 123 I]iodoamphetamine in rat brains were determined by serial measurements of brain uptake index (BUI) after intracarotid injection; also studied were its effects on amine uptake and release in rat's brain cortical synaptosomes; and its in vivo distribution in the dog and monkey. No specific localization in brain nuclei of the dog was seen, but there was progressive accumulation in the eyes. Rapid initial brain uptake in the ketamine-sedated monkey was noted, and further slow brain uptake occurred during the next 20 min but without retinal localization. High levels of brain activity were maintained for several hours. The quantitative initial single-pass clearance of the agent in the brain suggests its use in evaluation of regional brain perfusion. Its interaction with brain amine-binding sites suggests its possible application in studies of cerebral amine metabolism

  2. Age- and brain region-dependent α-synuclein oligomerization is attributed to alterations in intrinsic enzymes regulating α-synuclein phosphorylation in aging monkey brains.

    Science.gov (United States)

    Chen, Min; Yang, Weiwei; Li, Xin; Li, Xuran; Wang, Peng; Yue, Feng; Yang, Hui; Chan, Piu; Yu, Shun

    2016-02-23

    We previously reported that the levels of α-syn oligomers, which play pivotal pathogenic roles in age-related Parkinson's disease (PD) and dementia with Lewy bodies, increase heterogeneously in the aging brain. Here, we show that exogenous α-syn incubated with brain extracts from older cynomolgus monkeys and in Lewy body pathology (LBP)-susceptible brain regions (striatum and hippocampus) forms higher amounts of phosphorylated and oligomeric α-syn than that in extracts from younger monkeys and LBP-insusceptible brain regions (cerebellum and occipital cortex). The increased α-syn phosphorylation and oligomerization in the brain extracts from older monkeys and in LBP-susceptible brain regions were associated with higher levels of polo-like kinase 2 (PLK2), an enzyme promoting α-syn phosphorylation, and lower activity of protein phosphatase 2A (PP2A), an enzyme inhibiting α-syn phosphorylation, in these brain extracts. Further, the extent of the age- and brain-dependent increase in α-syn phosphorylation and oligomerization was reduced by inhibition of PLK2 and activation of PP2A. Inversely, phosphorylated α-syn oligomers reduced the activity of PP2A and showed potent cytotoxicity. In addition, the activity of GCase and the levels of ceramide, a product of GCase shown to activate PP2A, were lower in brain extracts from older monkeys and in LBP-susceptible brain regions. Our results suggest a role for altered intrinsic metabolic enzymes in age- and brain region-dependent α-syn oligomerization in aging brains.

  3. Hyperphosphorylated tau in the brains of mice and monkeys with long-term administration of ketamine.

    Science.gov (United States)

    Yeung, L Y; Wai, Maria S M; Fan, Ming; Mak, Y T; Lam, W P; Li, Zhen; Lu, Gang; Yew, David T

    2010-03-15

    Ketamine, a non-competitive antagonist at the glutamatergic N-methyl-d-aspartate (NMDA) receptor, might impair memory function of the brain. Loss of memory is also a characteristic of aging and Alzheimer's disease. Hyperphosphorylation of tau is an early event in the aging process and Alzheimer's disease. Therefore, we aimed to find out whether long-term ketmaine administration is related to hyperphosphorylation of tau or not in the brains of mice and monkeys. Results showed that after 6 months' administration of ketamine, in the prefrontal and entorhinal cortical sections of mouse and monkey brains, there were significant increases of positive sites for the hyperphosphorylated tau protein as compared to the control animals receiving no ketamine administration. Furthermore, about 15% of hyperphosphorylated tau positive cells were also positively labeled by terminal dUTP nick end labeling (TUNEL) indicating there might be a relationship between hyperphosphorylation of tau and apoptosis. Therefore, the long-term ketamine toxicity might involve neurodegenerative process similar to that of aging and/or Alzheimer's disease. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  4. Restoring voluntary control of locomotion after paralyzing spinal cord injury

    NARCIS (Netherlands)

    van den Brand, Rubia; Heutschi, Janine; Barraud, Quentin; DiGiovanna, Jack; Bartholdi, Kay; Huerlimann, Michèle; Friedli, Lucia; Vollenweider, Isabel; Moraud, Eduardo Martin; Duis, Simone; Dominici, Nadia; Micera, Silvestro; Musienko, Pavel; Courtine, Grégoire

    2012-01-01

    Half of human spinal cord injuries lead to chronic paralysis. Here, we introduce an electrochemical neuroprosthesis and a robotic postural interface designed to encourage supraspinally mediated movements in rats with paralyzing lesions. Despite the interruption of direct supraspinal pathways, the

  5. Phenobarbital increases monkey in vivo nicotine disposition and induces liver and brain CYP2B6 protein

    Science.gov (United States)

    Lee, Anna M; Miksys, Sharon; Tyndale, Rachel F

    2006-01-01

    CYP2B6 is a drug-metabolizing enzyme expressed in the liver and brain that can metabolize bupropion (Zyban®, a smoking cessation drug), activate tobacco-smoke nitrosamines, and inactivate nicotine. Hepatic CYP2B6 is induced by phenobarbital and induction may affect in vivo nicotine disposition, while brain CYP2B6 induction may affect local levels of centrally acting substrates. We investigated the effect of chronic phenobarbital treatment on induction of in vivo nicotine disposition and CYP2B6 expression in the liver and brain of African Green (Vervet) monkeys. Monkeys were split into two groups (n=6 each) and given oral saccharin daily for 22 days; one group was supplemented with 20 mg kg−1 phenobarbital. Monkeys were given a 0.1 mg kg−1 nicotine dose subcutaneously before and after treatment. Phenobarbital treatment resulted in a significant, 56%, decrease (P=0.04) in the maximum nicotine plasma concentration and a 46% decrease (P=0.003) in the area under the concentration–time curve. Phenobarbital also increased hepatic CYP2B6 protein expression. In monkey brain, significant induction (Pphenobarbital treatment in monkeys resulted in increased in vivo nicotine disposition, and induced hepatic and brain CYP2B6 protein levels and cellular expression. This induction may alter the metabolism of CYP2B6 substrates including peripherally acting drugs such as cyclophosphamide and centrally acting drugs such as bupropion, ecstasy and phencyclidine. PMID:16751792

  6. 31P saturation transfer and phosphocreatine imaging in the monkey brain

    International Nuclear Information System (INIS)

    Mora, B.; Narasimhan, P.T.; Ross, B.D.; Allman, J.; Barker, P.B.

    1991-01-01

    31 P magnetic resonance imaging with chemical-shift discrimination by selective excitation has been employed to determine the phosphocreatine (PCr) distribution in the brains of three juvenile macaque monkeys. PCr images were also obtained while saturating the resonance of the γ-phosphate of ATP, which allowed the investigation of the chemical exchange between PCr and the γ-phosphate of ATP catalyzed by creatine kinase. Superposition of the PCr images over the proton image of the same monkey brain revealed topological variations in the distribution of PCr and creatine kinase activity. PCr images were also obtained with and without visual stimulation. In two out of four experiments, an apparently localized decrease in PCr concentration was noted in visual cortex upon visual stimulation. This result is interpreted in terms of a possible role for the local ADP concentration in stimulating the accompanying metabolic response

  7. Control of Working Memory in Rhesus Monkeys (Macaca mulatta)

    Science.gov (United States)

    Tu, Hsiao-Wei; Hampton, Robert R.

    2014-01-01

    Cognitive control is critical for efficiently using the limited resources in working memory. It is well established that humans use rehearsal to increase the probability of remembering needed information, but little is known in nonhumans, with some studies reporting the absence of active control and others subject to alternative explanations. We trained monkeys in a visual matching-to-sample paradigm with a post-sample memory cue. Monkeys either saw a remember cue that predicted the occurrence of a matching test that required memory for the sample, or a forget cue that predicted a discrimination test that did not require memory of the sample. Infrequent probe trials on which monkeys were given tests of the type not cued on that trial were used to assess whether memory was under cognitive control. Our procedures controlled for reward expectation and for the surprising nature of the probes. Monkeys matched less accurately after forget cues, while discrimination accuracy was equivalent in the two cue conditions. We also tested monkeys with lists of two consecutive sample images that shared the same cue. Again, memory for expected memory tests was superior to that on unexpected tests. Together these results show that monkeys cognitively control their working memory. PMID:25436219

  8. Imaging for metabotropic glutamate receptor subtype 1 in rat and monkey brains using PET with [18F]FITM.

    Science.gov (United States)

    Yamasaki, Tomoteru; Fujinaga, Masayuki; Maeda, Jun; Kawamura, Kazunori; Yui, Joji; Hatori, Akiko; Yoshida, Yuichiro; Nagai, Yuji; Tokunaga, Masaki; Higuchi, Makoto; Suhara, Tetsuya; Fukumura, Toshimitsu; Zhang, Ming-Rong

    2012-04-01

    In this study, we evaluate the utility of 4-[(18)F]fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ([(18)F]FITM) as a positron emission tomography (PET) ligand for imaging of the metabotropic glutamate receptor subtype 1 (mGluR1) in rat and monkey brains. In vivo distribution of [(18)F]FITM in brains was evaluated by PET scans with or without the mGluR1-selective antagonist (JNJ16259685). Kinetic parameters of monkey PET data were obtained using the two-tissue compartment model with arterial blood sampling. In PET studies in rat and monkey brains, the highest uptake of radioactivity was in the cerebellum, followed by moderate uptake in the thalamus, hippocampus and striatum. The lowest uptake of radioactivity was detected in the pons. These uptakes in all brain regions were dramatically decreased by pre-administration of JNJ16259685. In kinetic analysis of monkey PET, the highest volume of distribution (V(T)) was detected in the cerebellum (V(T) = 11.5). [(18)F]FITM has an excellent profile as a PET ligand for mGluR1 imaging. PET with [(18)F]FITM may prove useful for determining the regional distribution and density of mGluR1 and the mGluR1 occupancy of drugs in human brains.

  9. PET study of the distribution of [11C]fluoxetine in a monkey brain

    International Nuclear Information System (INIS)

    Shiue, C.-Y.; Shiue, Grace G.; Cornish, Kurtis G.; O'Rourke, Maria F.

    1995-01-01

    No-carrier-added [ 11 C]fluoxetine (2) was synthesized by methylation of norfluoxetine (1) with [ 11 C]H 3 I in 20% radiochemical yield in a synthesis time of 40 min from EOB with a specific activity of 0.48 Ci/μM (EOB). In vivo study in mouse indicated that the uptake of 2 in mouse tissues was high and the radioactivity remained constant throughout the study. The uptake of 2 in mouse brain was 4%/g. PET study in a Rhesus monkey also showed that the uptakes of 2 in different brain regions were similar and the retention of radioactivity in these regions remained constant throughout the study (80 min). Analysis of arterial plasma by HPLC showed that only 20% of radioactivity in the plasma remained as 2 at 30 min post-injection. These results suggest that the uptake of fluoxetine in monkey brain is probably not receptor mediated. Rather, blood flow, lipophilicity or other transport mechanisms may play a role in its uptake

  10. Progress for the Paralyzed

    Science.gov (United States)

    ... Contents Latest Advances Help People Regain Function and Independence Founded in 2000, the National Institute for Biomedical ... More "NIBIB Robotics" Articles Progress for the Paralyzed / College Athlete Stands Again…On His Own! / Coffee to ...

  11. Neural control of finger movement via intracortical brain-machine interface

    Science.gov (United States)

    Irwin, Z. T.; Schroeder, K. E.; Vu, P. P.; Bullard, A. J.; Tat, D. M.; Nu, C. S.; Vaskov, A.; Nason, S. R.; Thompson, D. E.; Bentley, J. N.; Patil, P. G.; Chestek, C. A.

    2017-12-01

    Objective. Intracortical brain-machine interfaces (BMIs) are a promising source of prosthesis control signals for individuals with severe motor disabilities. Previous BMI studies have primarily focused on predicting and controlling whole-arm movements; precise control of hand kinematics, however, has not been fully demonstrated. Here, we investigate the continuous decoding of precise finger movements in rhesus macaques. Approach. In order to elicit precise and repeatable finger movements, we have developed a novel behavioral task paradigm which requires the subject to acquire virtual fingertip position targets. In the physical control condition, four rhesus macaques performed this task by moving all four fingers together in order to acquire a single target. This movement was equivalent to controlling the aperture of a power grasp. During this task performance, we recorded neural spikes from intracortical electrode arrays in primary motor cortex. Main results. Using a standard Kalman filter, we could reconstruct continuous finger movement offline with an average correlation of ρ  =  0.78 between actual and predicted position across four rhesus macaques. For two of the monkeys, this movement prediction was performed in real-time to enable direct brain control of the virtual hand. Compared to physical control, neural control performance was slightly degraded; however, the monkeys were still able to successfully perform the task with an average target acquisition rate of 83.1%. The monkeys’ ability to arbitrarily specify fingertip position was also quantified using an information throughput metric. During brain control task performance, the monkeys achieved an average 1.01 bits s-1 throughput, similar to that achieved in previous studies which decoded upper-arm movements to control computer cursors using a standard Kalman filter. Significance. This is, to our knowledge, the first demonstration of brain control of finger-level fine motor skills. We believe

  12. Paralyzed Veterans of America

    Science.gov (United States)

    ... Connected Twitter @PVA1946 Facebook @Paralyzed Veterans of America Instagram @PVA1946 National Veterans Wheelchair Games App Download Now ... 838-7782 CONNECT WITH US Facebook Twitter YouTube Instagram Flickr STAY INFORMED WITH NEWS & UPDATES Enter your ...

  13. Multidimensional control using a mobile-phone based brain-muscle-computer interface.

    Science.gov (United States)

    Vernon, Scott; Joshi, Sanjay S

    2011-01-01

    Many well-known brain-computer interfaces measure signals at the brain, and then rely on the brain's ability to learn via operant conditioning in order to control objects in the environment. In our lab, we have been developing brain-muscle-computer interfaces, which measure signals at a single muscle and then rely on the brain's ability to learn neuromuscular skills via operant conditioning. Here, we report a new mobile-phone based brain-muscle-computer interface prototype for severely paralyzed persons, based on previous results from our group showing that humans may actively create specified power levels in two separate frequency bands of a single sEMG signal. Electromyographic activity on the surface of a single face muscle (Auricularis superior) is recorded with a standard electrode. This analog electrical signal is imported into an Android-based mobile phone. User-modulated power in two separate frequency band serves as two separate and simultaneous control channels for machine control. After signal processing, the Android phone sends commands to external devices via Bluetooth. Users are trained to use the device via biofeedback, with simple cursor-to-target activities on the phone screen.

  14. Multi circular-cavity surface coil for magnetic resonance imaging of monkey's brain at 4 Tesla

    Science.gov (United States)

    Osorio, A. I.; Solis-Najera, S. E.; Vázquez, F.; Wang, R. L.; Tomasi, D.; Rodriguez, A. O.

    2014-11-01

    Animal models in medical research has been used to study humans diseases for several decades. The use of different imaging techniques together with different animal models offers a great advantage due to the possibility to study some human pathologies without the necessity of chirurgical intervention. The employ of magnetic resonance imaging for the acquisition of anatomical and functional images is an excellent tool because its noninvasive nature. Dedicated coils to perform magnetic resonance imaging experiments are obligatory due to the improvement on the signal-to-noise ratio and reduced specific absorption ratio. A specifically designed surface coil for magnetic resonance imaging of monkey's brain is proposed based on the multi circular-slot coil. Numerical simulations of the magnetic and electric fields were also performed using the Finite Integration Method to solve Maxwell's equations for this particular coil design and, to study the behavior of various vector magnetic field configurations and specific absorption ratio. Monkey's brain images were then acquired with a research-dedicated magnetic resonance imaging system at 4T, to evaluate the anatomical images with conventional imaging sequences. This coil showed good quality images of a monkey's brain and full compatibility with standard pulse sequences implemented in research-dedicated imager.

  15. Design and simulation of virtual telephone keypad control based on brain computer interface (BCI with very high transfer rates

    Directory of Open Access Journals (Sweden)

    Rehab B. Ashari

    2011-03-01

    Full Text Available Brain Computer Interface (BCI is a communication and control mechanism, which does not rely on any kind of muscular response to send a message to the external world. This technique is used to help the paralyzed people with spinal cord injury to have the ability to communicate with the external world. In this paper we emphasize to increase the BCI System bit rate for controlling a virtual telephone keypad. To achieve the proposed algorithm, a simulated virtual telephone keypad based on Steady State Visual Evoked Potential (SSVEP BCI system is developed. Dynamic programming technique with specifically modified Longest Common Subsequence (LCS algorithm is used. By comparing the paralyzed user selection with the recent, and then the rest, of the stored records in the file of the telephone, the user can save the rest of his choices for controlling the keypad and thence improving the overall performance of the BCI system. This axiomatic approach, which is used in searching the web pages for increasing the performance of the searching, is urgent to be used for the paralyzed people rather than the normal user.

  16. Synthesis and characterization in monkey of [{sup 11}C]SP203 as a radioligand for imaging brain metabotropic glutamate 5 receptors

    Energy Technology Data Exchange (ETDEWEB)

    Simeon, Fabrice G.; Liow, Jeih-San; Zhang, Yi; Hong, Jinsoo; Gladding, Robert L.; Zoghbi, Sami S.; Innis, Robert B.; Pike, Victor W. [National Institutes of Health, Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD (United States)

    2012-12-15

    [{sup 18}F]SP203 (3-fluoro-5-(2-(2-([{sup 18}F]fluoromethyl)-thiazol-4-yl)ethynyl)benzonitrile) is an effective high-affinity and selective radioligand for imaging metabotropic 5 receptors (mGluR5) in human brain with PET. To provide a radioligand that may be used for more than one scanning session in the same subject in a single day, we set out to label SP203 with shorter-lived {sup 11}C (t{sub 1/2} = 20.4 min) and to characterize its behavior as a radioligand with PET in the monkey. Iodo and bromo precursors were obtained by cross-coupling 2-fluoromethyl-4-((trimethylsilyl)ethynyl)-1,3-thiazole with 3,5-diiodofluorobenzene and 3,5-dibromofluorobenzene, respectively. Treatment of either precursor with [{sup 11}C]cyanide ion rapidly gave [{sup 11}C]SP203, which was purified with high-performance liquid chromatography. PET was used to measure the uptake of radioactivity in brain regions after injecting [{sup 11}C]SP203 intravenously into rhesus monkeys at baseline and under conditions in which mGluR5 were blocked with 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP). The emergence of radiometabolites in monkey blood in vitro and in vivo was assessed with radio-HPLC. The stability of [{sup 11}C]SP203 in human blood in vitro was also measured. The iodo precursor gave [{sup 11}C]SP203 in higher radiochemical yield (>98 %) than the bromo precursor (20-52 %). After intravenous administration of [{sup 11}C]SP203 into three rhesus monkeys, radioactivity peaked early in brain (average 12.5 min) with a regional distribution in rank order of expected mGluR5 density. Peak uptake was followed by a steady decline. No radioactivity accumulated in the skull. In monkeys pretreated with MTEP before [{sup 11}C]SP203 administration, radioactivity uptake in brain was again high but then declined more rapidly than in the baseline scan to a common low level. [{sup 11}C]SP203 was unstable in monkey blood in vitro and in vivo, and gave predominantly less lipophilic radiometabolites

  17. Mathematical models of human paralyzed muscle after long-term training.

    Science.gov (United States)

    Law, L A Frey; Shields, R K

    2007-01-01

    Spinal cord injury (SCI) results in major musculoskeletal adaptations, including muscle atrophy, faster contractile properties, increased fatigability, and bone loss. The use of functional electrical stimulation (FES) provides a method to prevent paralyzed muscle adaptations in order to sustain force-generating capacity. Mathematical muscle models may be able to predict optimal activation strategies during FES, however muscle properties further adapt with long-term training. The purpose of this study was to compare the accuracy of three muscle models, one linear and two nonlinear, for predicting paralyzed soleus muscle force after exposure to long-term FES training. Further, we contrasted the findings between the trained and untrained limbs. The three models' parameters were best fit to a single force train in the trained soleus muscle (N=4). Nine additional force trains (test trains) were predicted for each subject using the developed models. Model errors between predicted and experimental force trains were determined, including specific muscle force properties. The mean overall error was greatest for the linear model (15.8%) and least for the nonlinear Hill Huxley type model (7.8%). No significant error differences were observed between the trained versus untrained limbs, although model parameter values were significantly altered with training. This study confirmed that nonlinear models most accurately predict both trained and untrained paralyzed muscle force properties. Moreover, the optimized model parameter values were responsive to the relative physiological state of the paralyzed muscle (trained versus untrained). These findings are relevant for the design and control of neuro-prosthetic devices for those with SCI.

  18. Inter-species activity correlations reveal functional correspondences between monkey and human brain areas

    Science.gov (United States)

    Mantini, Dante; Hasson, Uri; Betti, Viviana; Perrucci, Mauro G.; Romani, Gian Luca; Corbetta, Maurizio; Orban, Guy A.; Vanduffel, Wim

    2012-01-01

    Evolution-driven functional changes in the primate brain are typically assessed by aligning monkey and human activation maps using cortical surface expansion models. These models use putative homologous areas as registration landmarks, assuming they are functionally correspondent. In cases where functional changes have occurred in an area, this assumption prohibits to reveal whether other areas may have assumed lost functions. Here we describe a method to examine functional correspondences across species. Without making spatial assumptions, we assess similarities in sensory-driven functional magnetic resonance imaging responses between monkey (Macaca mulatta) and human brain areas by means of temporal correlation. Using natural vision data, we reveal regions for which functional processing has shifted to topologically divergent locations during evolution. We conclude that substantial evolution-driven functional reorganizations have occurred, not always consistent with cortical expansion processes. This novel framework for evaluating changes in functional architecture is crucial to building more accurate evolutionary models. PMID:22306809

  19. PET study of the distribution of [{sup 11}C]fluoxetine in a monkey brain

    Energy Technology Data Exchange (ETDEWEB)

    Shiue, C.-Y.; Shiue, Grace G.; Cornish, Kurtis G.; O' Rourke, Maria F

    1995-07-01

    No-carrier-added [{sup 11}C]fluoxetine (2) was synthesized by methylation of norfluoxetine (1) with [{sup 11}C]H{sub 3}I in 20% radiochemical yield in a synthesis time of 40 min from EOB with a specific activity of 0.48 Ci/{mu}M (EOB). In vivo study in mouse indicated that the uptake of 2 in mouse tissues was high and the radioactivity remained constant throughout the study. The uptake of 2 in mouse brain was 4%/g. PET study in a Rhesus monkey also showed that the uptakes of 2 in different brain regions were similar and the retention of radioactivity in these regions remained constant throughout the study (80 min). Analysis of arterial plasma by HPLC showed that only 20% of radioactivity in the plasma remained as 2 at 30 min post-injection. These results suggest that the uptake of fluoxetine in monkey brain is probably not receptor mediated. Rather, blood flow, lipophilicity or other transport mechanisms may play a role in its uptake.

  20. Temporal coding of brain patterns for direct limb control in humans

    Directory of Open Access Journals (Sweden)

    Gernot Mueller-Putz

    2010-06-01

    Full Text Available For individuals with a high spinal cord injury (SCI not only the lower limbs, but also the upper extremities are paralyzed. A neuroprosthesis can be used to restore the lost hand and arm function in those tetraplegics. The main problem for this group of individuals, however, is the reduced ability to voluntarily operate device controllers. A Brain-Computer Interface provides a non-manual alternative to conventional input devices by translating brain activity patterns into control commands. We show that the temporal coding of individual mental imagery pattern can be used to control two independent degrees of freedom – grasp and elbow function - of an artificial robotic arm by utilizing a minimum number of EEG scalp electrodes. We describe the procedure from the initial screening to the final application. From eight naïve subjects participating on-line feedback experiments, four were able to voluntarily control an artificial arm by inducing one motor imagery pattern derived from one EEG derivation only.

  1. Maternal antibodies from mothers of children with autism alter brain growth and social behavior development in the rhesus monkey.

    Science.gov (United States)

    Bauman, M D; Iosif, A-M; Ashwood, P; Braunschweig, D; Lee, A; Schumann, C M; Van de Water, J; Amaral, D G

    2013-07-09

    Antibodies directed against fetal brain proteins of 37 and 73 kDa molecular weight are found in approximately 12% of mothers who have children with autism spectrum disorder (ASD), but not in mothers of typically developing children. This finding has raised the possibility that these immunoglobulin G (IgG) class antibodies cross the placenta during pregnancy and impact brain development, leading to one form of ASD. We evaluated the pathogenic potential of these antibodies by using a nonhuman primate model. IgG was isolated from mothers of children with ASD (IgG-ASD) and of typically developing children (IgG-CON). The purified IgG was administered to two groups of female rhesus monkeys (IgG-ASD; n=8 and IgG-CON; n=8) during the first and second trimesters of pregnancy. Another control group of pregnant monkeys (n=8) was untreated. Brain and behavioral development of the offspring were assessed for 2 years. Behavioral differences were first detected when the macaque mothers responded to their IgG-ASD offspring with heightened protectiveness during early development. As they matured, IgG-ASD offspring consistently deviated from species-typical social norms by more frequently approaching familiar peers. The increased approach was not reciprocated and did not lead to sustained social interactions. Even more striking, IgG-ASD offspring displayed inappropriate approach behavior to unfamiliar peers, clearly deviating from normal macaque social behavior. Longitudinal magnetic resonance imaging analyses revealed that male IgG-ASD offspring had enlarged brain volume compared with controls. White matter volume increases appeared to be driving the brain differences in the IgG-ASD offspring and these differences were most pronounced in the frontal lobes.

  2. Big data challenges in decoding cortical activity in a human with quadriplegia to inform a brain computer interface.

    Science.gov (United States)

    Friedenberg, David A; Bouton, Chad E; Annetta, Nicholas V; Skomrock, Nicholas; Mingming Zhang; Schwemmer, Michael; Bockbrader, Marcia A; Mysiw, W Jerry; Rezai, Ali R; Bresler, Herbert S; Sharma, Gaurav

    2016-08-01

    Recent advances in Brain Computer Interfaces (BCIs) have created hope that one day paralyzed patients will be able to regain control of their paralyzed limbs. As part of an ongoing clinical study, we have implanted a 96-electrode Utah array in the motor cortex of a paralyzed human. The array generates almost 3 million data points from the brain every second. This presents several big data challenges towards developing algorithms that should not only process the data in real-time (for the BCI to be responsive) but are also robust to temporal variations and non-stationarities in the sensor data. We demonstrate an algorithmic approach to analyze such data and present a novel method to evaluate such algorithms. We present our methodology with examples of decoding human brain data in real-time to inform a BCI.

  3. The Desire for Amputation or Paralyzation : Evidence for Structural Brain Anomalies in Body Integrity Identity Disorder (BIID)

    NARCIS (Netherlands)

    Blom, Rianne M; van Wingen, Guido A; van der Wal, Sija J; Luigjes, Judy; van Dijk, Milenna T; Scholte, H Steven; Denys, D.

    2016-01-01

    BACKGROUND: Body Integrity Identity Disorder (BIID) is a condition in which individuals perceive a mismatch between their internal body scheme and physical body shape, resulting in an absolute desire to be either amputated or paralyzed. The condition is hypothesized to be of congenital nature, but

  4. Comparative PET studies of the distribution of ( - )-3,4-methylenedioxy-N-[11C]methamphetamine and ( - )-[11C]methamphetamine in a monkey brain

    International Nuclear Information System (INIS)

    Shiue Chyngyann; Shiue, Grace G.; Cornish, Kurtis G.; O'Rourke, Maria F.

    1995-01-01

    Carbon-11 labeled ( - )-methamphetamine and ( - )-3,4-methylenedioxy-N-methamphetamine were synthesized by methylation of the corresponding desmethyl precursors with [ 11 C]H 3 I in 40-60% yield in a synthesis time of 30 min from EOB with a specific activity of 0.5-1.2 Ci/μM. PET studies in a Rhesus monkey revealed that the uptakes of both compounds in different brain regions were similar, and the retention of radioactivity in these brain regions remained constant throughout the study for the former while it was washed out slowly for the latter. The half-life of ( - )-3,4-methylenedioxy-N-methamphetamine in monkey brain was approximately 70 min. Analyses of arterial plasma by HPLC revealed that 50% of radioactivity in the plasma remained as ( - )-methamphetamine while only 3% remained as ( - )-3,4-methylenedioxy-N-methamphetamine at 60 min post-injection. These results suggest that the uptakes of both compounds in monkey brain are probably not receptor mediated. Rather, blood flow, lipophilicity of the compounds or other transport mechanisms may play a role in their uptakes

  5. Differential Temporal Evolution Patterns in Brain Temperature in Different Ischemic Tissues in a Monkey Model of Middle Cerebral Artery Occlusion

    Directory of Open Access Journals (Sweden)

    Zhihua Sun

    2012-01-01

    Full Text Available Brain temperature is elevated in acute ischemic stroke, especially in the ischemic penumbra (IP. We attempted to investigate the dynamic evolution of brain temperature in different ischemic regions in a monkey model of middle cerebral artery occlusion. The brain temperature of different ischemic regions was measured with proton magnetic resonance spectroscopy (1H MRS, and the evolution processes of brain temperature were compared among different ischemic regions. We found that the normal (baseline brain temperature of the monkey brain was 37.16°C. In the artery occlusion stage, the mean brain temperature of ischemic tissue was 1.16°C higher than the baseline; however, this increase was region dependent, with 1.72°C in the IP, 1.08°C in the infarct core, and 0.62°C in the oligemic region. After recanalization, the brain temperature of the infarct core showed a pattern of an initial decrease accompanied by a subsequent increase. However, the brain temperature of the IP and oligemic region showed a monotonously and slowly decreased pattern. Our study suggests that in vivo measurement of brain temperature could help to identify whether ischemic tissue survives.

  6. The Desire for Amputation or Paralyzation: Evidence for Structural Brain Anomalies in Body Integrity Identity Disorder (BIID)

    NARCIS (Netherlands)

    Blom, Rianne M.; van Wingen, Guido A.; van der Wal, Sija J.; Luigjes, Judy; van Dijk, Milenna T.; Scholte, H. Steven; Denys, Damiaan

    2016-01-01

    Body Integrity Identity Disorder (BIID) is a condition in which individuals perceive a mismatch between their internal body scheme and physical body shape, resulting in an absolute desire to be either amputated or paralyzed. The condition is hypothesized to be of congenital nature, but evidence for

  7. Magnetic Resonance Imaging of Japanese monkey brains compared with X-ray photography and histology

    International Nuclear Information System (INIS)

    Kaji, Shinji; Matsuda, Keiji; Kawano, Kenji; Komatsu, Hidehiko; Yamane, Shigeru; Yoshizawa, Takashi; Nose, Tadao.

    1991-01-01

    The localization of a small target area in the brain is usually estimated by using stereotaxic atlases, assisted by X-ray photography or electrophysiological mapping, and determined finally by histological reconstruction. Magnetic Resonance Imaging (MRI) can visualize, noninvasively cross sections in any plane of three dimensional structures of the brain. We compared images of MRI, X-ray, and histology from a monkey brain. A Japanese monkey (Macaca fuscata, male, 11 kg) was anesthetised, fixed in a newly developed magnetic-free stereotaxic apparatus, and mounted in the MRI scanner unit (BRUKER, BIOSPEC 24/40, 2.4 Tesla). Some para-saggital (5 mm thick) and para-frontal (2.5 mm thick, every 5 mm distance) images were obtained. The outline of the bone on the MRI image was compared with that on the X-ray photograph taken by an X-ray instrument (Toshiba, TR-80A). The two images fitted very well. The animal was sacrificed, the brain was sliced in 100 μm and stained with Cresyl violet. The histological preparations were shrunk some 10 % during the process, which was revealed by comparison of MRI, X-ray, and histological images. In conclusion, MRI images are reliable enough to determine a small target in deep structures of the brain, and their superimposed images on X-rays will assist in identifying the location of electrode or needle tips. We constructed a data base of these MRI and histological images on a Macintosh computer, and they can be easily accessed by a mouse operation. (author)

  8. Integrating histology and MRI in the first digital brain of common squirrel monkey, Saimiri sciureus

    Science.gov (United States)

    Sun, Peizhen; Parvathaneni, Prasanna; Schilling, Kurt G.; Gao, Yurui; Janve, Vaibhav; Anderson, Adam; Landman, Bennett A.

    2015-03-01

    This effort is a continuation of development of a digital brain atlas of the common squirrel monkey, Saimiri sciureus, a New World monkey with functional and microstructural organization of central nervous system similar to that of humans. Here, we present the integration of histology with multi-modal magnetic resonance imaging (MRI) atlas constructed from the brain of an adult female squirrel monkey. The central concept of this work is to use block face photography to establish an intermediate common space in coordinate system which preserves the high resolution in-plane resolution of histology while enabling 3-D correspondence with MRI. In vivo MRI acquisitions include high resolution T2 structural imaging (300 μm isotropic) and low resolution diffusion tensor imaging (600 um isotropic). Ex vivo MRI acquisitions include high resolution T2 structural imaging and high resolution diffusion tensor imaging (both 300 μm isotropic). Cortical regions were manually annotated on the co-registered volumes based on published histological sections in-plane. We describe mapping of histology and MRI based data of the common squirrel monkey and construction of a viewing tool that enable online viewing of these datasets. The previously descried atlas MRI is used for its deformation to provide accurate conformation to the MRI, thus adding information at the histological level to the MRI volume. This paper presents the mapping of single 2D image slice in block face as a proof of concept and this can be extended to map the atlas space in 3D coordinate system as part of the future work and can be loaded to an XNAT system for further use.

  9. [Totally paralyzed or brain dead?

    NARCIS (Netherlands)

    Dijk, G.W. van; Vos, P.E.; Eurelings, M.; Jansen, G.H.; Gijn, J. van

    2001-01-01

    In two patients, men aged 23 and 42 years, a condition that mimicked brain death was observed as a consequence of rapidly progressive complete peripheral paralyses, which included the intrinsic and extrinsic eye muscles. However, the EEG revealed a waking pattern. Maximal supportive therapy was

  10. Dual-isotope single-photon emission computed tomography for dopamine and serotonin transporters in normal and parkinsonian monkey brains

    International Nuclear Information System (INIS)

    Li, I-H.; Huang, W.-S.; Yeh, C.-B.; Liao, M.-H.; Chen, C.-C.; Shen, L.-H.; Liu, J.-C.; Ma, K.-H.

    2009-01-01

    Introduction: Parkinson's disease (PD) affects both dopaminergic and serotonergic systems. In this study, we simultaneously evaluated dopamine and serotonin transporters in primates using dual-isotope single-photon emission computed tomography (SPECT) imaging and compared the results with traditional single-isotope imaging. Methods: Four healthy and one 6-OHDA-induced PD monkeys were used for this study. SPECT was performed over 4 h after individual or simultaneous injection of [ 99m Tc]TRODAT-1 (a dopamine transporter imaging agent) and [ 123 I]ADAM (a serotonin transporter imaging agent). Results: The results showed that the image quality and uptake ratios in different brain regions were comparable between single- and dual-isotope studies. The striatal [ 99m Tc]TRODAT-1 uptake in the PD monkey was markedly lower than that in normal monkeys. The uptake of [ 123 I]ADAM in the midbrain of the PD monkey was comparable to that in the normal monkeys, but there were decreased uptakes in the thalamus and striatum of the PD monkey. Conclusions: Our results suggest that dual-isotope SPECT using [ 99m Tc]TRODAT-1 and [ 123 I]ADAM can simultaneously evaluate changes in dopaminergic and serotonergic systems in a PD model.

  11. Blood to brain iron uptake in one Rhesus monkey using [Fe-52]-citrate and positron emission tomography (PET): influence of haloperidol

    Energy Technology Data Exchange (ETDEWEB)

    Leenders, K L [Paul Scherrer Inst., Villigen (Switzerland); [Neurology Dept., Univ. Hospital, Zuerich (Switzerland); Antonini, A; Schwarzbach, R; Smith-Jones, P; Reist, H [Paul Scherrer Inst., Villigen (Switzerland); Youdim, M [Pharmacology Dept., Technion, Haifa (Israel); Henn, V [Neurology Dept., Univ. Hospital, Zuerich (Switzerland)

    1994-12-31

    Iron is highly concentrated in the basal ganglia of the brain. The involvement of cerebral iron and its handling systems in neurodegenerative brain diseases like Parkinson`s disease and tardive dyskinesia is currently under close investigation. There is evidence from animal studies that neuroleptics can increase iron uptake into brain. This effect appeared to be due to alteration of blood-brain barrier transport by the neuroleptics, particularly chlorpromazine and haloperidol, but not clozapine. We have investigated one Rhesus monkey using positron emission tomography (PET) and [Fe-52]-citrate before and during haloperidol administration. After drug withdrawal during a period of 1.5 year the investigation procedure was repeated. The results show that in the investigated monkey haloperidol induces a reversible marked increase of iron transport across the blood brain barrier concomitant with a large increase in elimination rate of the tracer from the blood. (author).

  12. Blood to brain iron uptake in one Rhesus monkey using [Fe-52]-citrate and positron emission tomography (PET): influence of haloperidol

    International Nuclear Information System (INIS)

    Leenders, K.L.; Antonini, A.; Schwarzbach, R.; Smith-Jones, P.; Reist, H.; Youdim, M.; Henn, V.

    1994-01-01

    Iron is highly concentrated in the basal ganglia of the brain. The involvement of cerebral iron and its handling systems in neurodegenerative brain diseases like Parkinson's disease and tardive dyskinesia is currently under close investigation. There is evidence from animal studies that neuroleptics can increase iron uptake into brain. This effect appeared to be due to alteration of blood-brain barrier transport by the neuroleptics, particularly chlorpromazine and haloperidol, but not clozapine. We have investigated one Rhesus monkey using positron emission tomography (PET) and [Fe-52]-citrate before and during haloperidol administration. After drug withdrawal during a period of 1.5 year the investigation procedure was repeated. The results show that in the investigated monkey haloperidol induces a reversible marked increase of iron transport across the blood brain barrier concomitant with a large increase in elimination rate of the tracer from the blood. (author)

  13. Precise and accurate assay of pregnenolone and five other neurosteroids in monkey brain tissue by LC-MS/MS.

    Science.gov (United States)

    Dury, Alain Y; Ke, Yuyong; Labrie, Fernand

    2016-09-01

    A series of steroids present in the brain have been named "neurosteroids" following the possibility of their role in the central nervous system impairments such as anxiety disorders, depression, premenstrual dysphoric disorder (PMDD), addiction, or even neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Study of their potential role requires a sensitive and accurate assay of their concentration in the monkey brain, the closest model to the human. We have thus developed a robust, precise and accurate liquid chromatography-tandem mass spectrometry method for the assay of pregnenolone, pregnanolone, epipregnanolone, allopregnanolone, epiallopregnanolone, and androsterone in the cynomolgus monkey brain. The extraction method includes a thorough sample cleanup using protein precipitation and phospholipid removal, followed by hexane liquid-liquid extraction and a Girard T ketone-specific derivatization. This method opens the possibility of investigating the potential implication of these six steroids in the most suitable animal model for neurosteroid-related research. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. DNA content of rodent brains during maturation and aging, and autoradiography of postnatal DNA synthesis in monkey brain

    International Nuclear Information System (INIS)

    Howard, E.

    1973-01-01

    [ 3 H]Thymidine is taken up by cells synthesizing DNA prepatory to cell division and remains incorporated in the DNA molecules as a lasting radioactive cell marker unless diluted out by repeated cell divisions. With the mouse and rat, histological studies after [ 3 H]thymidine injections have demonstrated that the cells of the external granular layer of the cerebellum proliferate abundantly during the first 2 weeks of postnatal life. Development of the primate brain is a gradual process extending over a much longer time than is required in the rodent. Despite the relative histological maturity of the monkey cerebellum at birth, the cells of the external granular layer are still actively synthesizing DNA at this time. Two monkeys were given [ 3 H]thymidine at birth and killed within 4 hours. Intense radioactivity was present in the cells of the external granular layer. Cells near the Prukinje perikarya were rather frequently labelled in this monkey, as described by Miale and Sidman in the mouse. In the molecular layer and in the body of the granular layer, relatively few cells were labelled. The labelling was present throughout the cerebellum, although the number of cells labelled varied from one microscopic field to another

  15. [11C]CHIBA-1001 as a novel PET ligand for alpha7 nicotinic receptors in the brain: a PET study in conscious monkeys.

    Directory of Open Access Journals (Sweden)

    Kenji Hashimoto

    Full Text Available BACKGROUND: The alpha7 nicotinic acetylcholine receptors (nAChRs play an important role in the pathophysiology of neuropsychiatric diseases such as schizophrenia and Alzheimer's disease. However, there are currently no suitable positron emission tomography (PET radioligands for imaging alpha7 nAChRs in the intact human brain. Here we report the novel PET radioligand [11C]CHIBA-1001 for in vivo imaging of alpha7 nAChRs in the non-human primate brain. METHODOLOGY/PRINCIPAL FINDINGS: A receptor binding assay showed that CHIBA-1001 was a highly selective ligand at alpha7 nAChRs. Using conscious monkeys, we found that the distribution of radioactivity in the monkey brain after intravenous administration of [11C]CHIBA-1001 was consistent with the regional distribution of alpha7 nAChRs in the monkey brain. The distribution of radioactivity in the brain regions after intravenous administration of [11C]CHIBA-1001 was blocked by pretreatment with the selective alpha7 nAChR agonist SSR180711 (5.0 mg/kg. However, the distribution of [11C]CHIBA-1001 was not altered by pretreatment with the selective alpha4beta2 nAChR agonist A85380 (1.0 mg/kg. Interestingly, the binding of [11C]CHIBA-1001 in the frontal cortex of the monkey brain was significantly decreased by subchronic administration of the N-methyl-D-aspartate (NMDA receptor antagonist phencyclidine (0.3 mg/kg, twice a day for 13 days; which is a non-human primate model of schizophrenia. CONCLUSIONS/SIGNIFICANCE: The present findings suggest that [11C]CHIBA-1001 could be a novel useful PET ligand for in vivo study of the receptor occupancy and pathophysiology of alpha7 nAChRs in the intact brain of patients with neuropsychiatric diseases such as schizophrenia and Alzheimer's disease.

  16. EXiO-A Brain-Controlled Lower Limb Exoskeleton for Rhesus Macaques.

    Science.gov (United States)

    Vouga, Tristan; Zhuang, Katie Z; Olivier, Jeremy; Lebedev, Mikhail A; Nicolelis, Miguel A L; Bouri, Mohamed; Bleuler, Hannes

    2017-02-01

    Recent advances in the field of brain-machine interfaces (BMIs) have demonstrated enormous potential to shape the future of rehabilitation and prosthetic devices. Here, a lower-limb exoskeleton controlled by the intracortical activity of an awake behaving rhesus macaque is presented as a proof-of-concept for a locomotorBMI. A detailed description of the mechanical device, including its innovative features and first experimental results, is provided. During operation, BMI-decoded position and velocity are directly mapped onto the bipedal exoskeleton's motions, which then move the monkey's legs as the monkey remains physicallypassive. To meet the unique requirements of such an application, the exoskeleton's features include: high output torque with backdrivable actuation, size adjustability, and safe user-robot interface. In addition, a novel rope transmission is introduced and implemented. To test the performance of the exoskeleton, a mechanical assessment was conducted, which yielded quantifiable results for transparency, efficiency, stiffness, and tracking performance. Usage under both brain control and automated actuation demonstrates the device's capability to fulfill the demanding needs of this application. These results lay the groundwork for further advancement in BMI-controlled devices for primates including humans.

  17. Dual-isotope single-photon emission computed tomography for dopamine and serotonin transporters in normal and parkinsonian monkey brains

    Energy Technology Data Exchange (ETDEWEB)

    Li, I-H. [Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan (China); Huang, W.-S. [Department of Nuclear Medicine, Tri-Service General Hospital, Taipei, 114, Taiwan (China); Yeh, C.-B. [Department of Psychiatry, Tri-Service General Hospital, Taipei, 114, Taiwan (China); Liao, M.-H.; Chen, C.-C.; Shen, L.-H. [Division of Isotope Application, Institute of Nuclear Energy Research, Taoyaun, 325 Taiwan (China); Liu, J.-C. [Department of Biology and Anatomy, National Defense Medical Center, Taipei 114, Taiwan (China); Ma, K.-H. [Department of Biology and Anatomy, National Defense Medical Center, Taipei 114, Taiwan (China)], E-mail: kuohsing91@yahoo.com.tw

    2009-08-15

    Introduction: Parkinson's disease (PD) affects both dopaminergic and serotonergic systems. In this study, we simultaneously evaluated dopamine and serotonin transporters in primates using dual-isotope single-photon emission computed tomography (SPECT) imaging and compared the results with traditional single-isotope imaging. Methods: Four healthy and one 6-OHDA-induced PD monkeys were used for this study. SPECT was performed over 4 h after individual or simultaneous injection of [{sup 99m}Tc]TRODAT-1 (a dopamine transporter imaging agent) and [{sup 123}I]ADAM (a serotonin transporter imaging agent). Results: The results showed that the image quality and uptake ratios in different brain regions were comparable between single- and dual-isotope studies. The striatal [{sup 99m}Tc]TRODAT-1 uptake in the PD monkey was markedly lower than that in normal monkeys. The uptake of [{sup 123}I]ADAM in the midbrain of the PD monkey was comparable to that in the normal monkeys, but there were decreased uptakes in the thalamus and striatum of the PD monkey. Conclusions: Our results suggest that dual-isotope SPECT using [{sup 99m}Tc]TRODAT-1 and [{sup 123}I]ADAM can simultaneously evaluate changes in dopaminergic and serotonergic systems in a PD model.

  18. Upregulation of Aβ42 in the Brain and Bodily Fluids of Rhesus Monkeys with Aging.

    Science.gov (United States)

    Zhao, Qiao; Lu, Jing; Yao, Zitong; Wang, Shubo; Zhu, Liming; Wang, Ju; Chen, Baian

    2017-01-01

    The cerebral accumulation of amyloid beta (Aβ) is one of the key pathological hallmarks of Alzheimer's disease (AD). Aβ is also found in bodily fluids such as the cerebrospinal fluid (CSF) and plasma. However, the significance of Aβ accumulation in the brain and different bodily pools, as well as its correlation with aging and cerebral amyloid pathology, is not completely understood. To better understand this question, we selected the rhesus monkey, which is phylogenetically and physiologically highly similar to the human, as a model to study. We quantified the levels of the two main Aβ isoforms (Aβ42 and Aβ40) in different sections of the brain (frontal cortex, temporal cortex, and hippocampus) and bodily fluids (CSF and plasma) of rhesus monkeys at different developmental phases (young, 5-9 years of age; mature, 10-19 years of age; and old, 21-24 years of age). We found that the levels of neuronal and insoluble Aβ42 increased significantly in the brain with aging, suggesting that this specific isoform might be directly involved in aging and AD-like pathophysiology. There was no significant change in the Aβ40 level in the brain with aging. In addition, the Aβ42 level, but not the Aβ40 level, in both the CSF and plasma increased with aging. We also identified a positive correlation between Aβ42 in the CSF and plasma and Aβ42 in the brain. Taken collectively, our results indicate that there is an association between Aβ accumulation and age. These results support the increased incidence of AD with aging.

  19. Comparative PET studies of the distribution of ( - )-3,4-methylenedioxy-N-[{sup 11}C]methamphetamine and ( - )-[{sup 11}C]methamphetamine in a monkey brain

    Energy Technology Data Exchange (ETDEWEB)

    Shiue Chyngyann; Shiue, Grace G.; Cornish, Kurtis G.; O' Rourke, Maria F

    1995-04-01

    Carbon-11 labeled ( - )-methamphetamine and ( - )-3,4-methylenedioxy-N-methamphetamine were synthesized by methylation of the corresponding desmethyl precursors with [{sup 11}C]H{sub 3}I in 40-60% yield in a synthesis time of 30 min from EOB with a specific activity of 0.5-1.2 Ci/{mu}M. PET studies in a Rhesus monkey revealed that the uptakes of both compounds in different brain regions were similar, and the retention of radioactivity in these brain regions remained constant throughout the study for the former while it was washed out slowly for the latter. The half-life of ( - )-3,4-methylenedioxy-N-methamphetamine in monkey brain was approximately 70 min. Analyses of arterial plasma by HPLC revealed that 50% of radioactivity in the plasma remained as ( - )-methamphetamine while only 3% remained as ( - )-3,4-methylenedioxy-N-methamphetamine at 60 min post-injection. These results suggest that the uptakes of both compounds in monkey brain are probably not receptor mediated. Rather, blood flow, lipophilicity of the compounds or other transport mechanisms may play a role in their uptakes.

  20. Functional Imaging of Audio–Visual Selective Attention in Monkeys and Humans: How do Lapses in Monkey Performance Affect Cross-Species Correspondences?

    Science.gov (United States)

    Muers, Ross S.; Salo, Emma; Slater, Heather; Petkov, Christopher I.

    2017-01-01

    Abstract The cross-species correspondences and differences in how attention modulates brain responses in humans and animal models are poorly understood. We trained 2 monkeys to perform an audio–visual selective attention task during functional magnetic resonance imaging (fMRI), rewarding them to attend to stimuli in one modality while ignoring those in the other. Monkey fMRI identified regions strongly modulated by auditory or visual attention. Surprisingly, auditory attention-related modulations were much more restricted in monkeys than humans performing the same tasks during fMRI. Further analyses ruled out trivial explanations, suggesting that labile selective-attention performance was associated with inhomogeneous modulations in wide cortical regions in the monkeys. The findings provide initial insights into how audio–visual selective attention modulates the primate brain, identify sources for “lost” attention effects in monkeys, and carry implications for modeling the neurobiology of human cognition with nonhuman animals. PMID:28419201

  1. Closed-loop control of spinal cord stimulation to restore hand function after paralysis

    Directory of Open Access Journals (Sweden)

    Jonas B Zimmermann

    2014-05-01

    Full Text Available As yet, no cure exists for upper-limb paralysis resulting from the damage to motor pathways after spinal cord injury or stroke. Recently, neural activity from the motor cortex of paralyzed individuals has been used to control the movements of a robot arm but restoring function to patients’ actual limbs remains a considerable challenge. Previously we have shown that electrical stimulation of the cervical spinal cord in anesthetized monkeys can elicit functional upper-limb movements like reaching and grasping. Here we show that stimulation can be controlled using cortical activity in awake animals to bypass disruption of the corticospinal system, restoring their ability to perform a simple upper-limb task. Monkeys were trained to grasp and pull a spring-loaded handle. After temporary paralysis of the hand was induced by reversible inactivation of primary motor cortex using muscimol, grasp-related single-unit activity from the ventral premotor cortex was converted into stimulation patterns delivered in real-time to the cervical spinal grey matter. During periods of closed-loop stimulation, task-modulated electromyogram, movement amplitude and task success rate were improved relative to interleaved control periods without stimulation. In some sessions, single motor unit activity from weakly active muscles was also used successfully to control stimulation. These results are the first use of a neural prosthesis to improve the hand function of primates after motor cortex disruption, and demonstrate the potential for closed-loop cortical control of spinal cord stimulation to reanimate paralyzed limbs.

  2. An EEG/EOG-based hybrid brain-neural computer interaction (BNCI) system to control an exoskeleton for the paralyzed hand.

    Science.gov (United States)

    Soekadar, Surjo R; Witkowski, Matthias; Vitiello, Nicola; Birbaumer, Niels

    2015-06-01

    The loss of hand function can result in severe physical and psychosocial impairment. Thus, compensation of a lost hand function using assistive robotics that can be operated in daily life is very desirable. However, versatile, intuitive, and reliable control of assistive robotics is still an unsolved challenge. Here, we introduce a novel brain/neural-computer interaction (BNCI) system that integrates electroencephalography (EEG) and electrooculography (EOG) to improve control of assistive robotics in daily life environments. To evaluate the applicability and performance of this hybrid approach, five healthy volunteers (HV) (four men, average age 26.5 ± 3.8 years) and a 34-year-old patient with complete finger paralysis due to a brachial plexus injury (BPI) used EEG (condition 1) and EEG/EOG (condition 2) to control grasping motions of a hand exoskeleton. All participants were able to control the BNCI system (BNCI control performance HV: 70.24 ± 16.71%, BPI: 65.93 ± 24.27%), but inclusion of EOG significantly improved performance across all participants (HV: 80.65 ± 11.28, BPI: 76.03 ± 18.32%). This suggests that hybrid BNCI systems can achieve substantially better control over assistive devices, e.g., a hand exoskeleton, than systems using brain signals alone and thus may increase applicability of brain-controlled assistive devices in daily life environments.

  3. Brain-Machine Interface control of a robot arm using actor-critic rainforcement learning.

    Science.gov (United States)

    Pohlmeyer, Eric A; Mahmoudi, Babak; Geng, Shijia; Prins, Noeline; Sanchez, Justin C

    2012-01-01

    Here we demonstrate how a marmoset monkey can use a reinforcement learning (RL) Brain-Machine Interface (BMI) to effectively control the movements of a robot arm for a reaching task. In this work, an actor-critic RL algorithm used neural ensemble activity in the monkey's motor cortext to control the robot movements during a two-target decision task. This novel approach to decoding offers unique advantages for BMI control applications. Compared to supervised learning decoding methods, the actor-critic RL algorithm does not require an explicit set of training data to create a static control model, but rather it incrementally adapts the model parameters according to its current performance, in this case requiring only a very basic feedback signal. We show how this algorithm achieved high performance when mapping the monkey's neural states (94%) to robot actions, and only needed to experience a few trials before obtaining accurate real-time control of the robot arm. Since RL methods responsively adapt and adjust their parameters, they can provide a method to create BMIs that are robust against perturbations caused by changes in either the neural input space or the output actions they generate under different task requirements or goals.

  4. Functional Imaging of Audio-Visual Selective Attention in Monkeys and Humans: How do Lapses in Monkey Performance Affect Cross-Species Correspondences?

    Science.gov (United States)

    Rinne, Teemu; Muers, Ross S; Salo, Emma; Slater, Heather; Petkov, Christopher I

    2017-06-01

    The cross-species correspondences and differences in how attention modulates brain responses in humans and animal models are poorly understood. We trained 2 monkeys to perform an audio-visual selective attention task during functional magnetic resonance imaging (fMRI), rewarding them to attend to stimuli in one modality while ignoring those in the other. Monkey fMRI identified regions strongly modulated by auditory or visual attention. Surprisingly, auditory attention-related modulations were much more restricted in monkeys than humans performing the same tasks during fMRI. Further analyses ruled out trivial explanations, suggesting that labile selective-attention performance was associated with inhomogeneous modulations in wide cortical regions in the monkeys. The findings provide initial insights into how audio-visual selective attention modulates the primate brain, identify sources for "lost" attention effects in monkeys, and carry implications for modeling the neurobiology of human cognition with nonhuman animals. © The Author 2017. Published by Oxford University Press.

  5. [Raman spectra of monkey cerebral cortex tissue].

    Science.gov (United States)

    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.

  6. The properties of B-form monoamine oxidase in mitochondria from monkey platelet.

    Science.gov (United States)

    Obata, Toshio; Aomine, Masahiro

    The present study was examined the effect of the properties of monkey platelet monoamine oxidase (MAO) based on inhibitor sensitivity. Monkey platelet showed a high MAO activity with beta-phenylethylamine (beta-PEA) as substrate and a very low A-form MAO activity with 5 hydroxytryptamine (5-HT) as substrate. Moreover, monkey platelet MAO was sensitive to the drugs deprenyl as B-form MAO inhibitor and less sensitive to clorgyline and harmaline as A form MAO inhibitor with beta-PEA as the B-form MAO substrate. B-form MAO from monkey platelet was more stable against heat treatment at 55 degrees C than B-form MAO in brain. After digestion with trypsin at 37 degrees C for 4 hrs, it was found that MAO from platelet was inhibited about 70% with beta-PEA as substrate with brain. The tricyclic antidepressant imipramine and nortriptyline inhibited B-form MAO activity more potency than B-form MAO in brain. However, when the noncyclic antidepressant nomifensine was used, monkey platelet B-form MAO activities were less potently inhibited. All these reagents were noncompetitive inhibitors of B form MAO in monkey platelet. The present studies demonstrated that monkey platelet MAO is a single of B-form MAO and sensitive to tricyclic antidepressants.

  7. The Desire for Amputation or Paralyzation: Evidence for Structural Brain Anomalies in Body Integrity Identity Disorder (BIID)

    OpenAIRE

    Blom, Rianne M; van Wingen, Guido A; van der Wal, Sija J; Luigjes, Judy; van Dijk, Milenna T; Scholte, H Steven; Denys, D.

    2016-01-01

    BACKGROUND: Body Integrity Identity Disorder (BIID) is a condition in which individuals perceive a mismatch between their internal body scheme and physical body shape, resulting in an absolute desire to be either amputated or paralyzed. The condition is hypothesized to be of congenital nature, but evidence for a neuro-anatomical basis is sparse. METHODS: We collected T1-weighted structural magnetic resonance imaging scans on a 3T scanner in eight individuals with BIID and 24 matched healthy c...

  8. Imaging of aromatase distribution in rat and rhesus monkey brains with [11C]vorozole

    International Nuclear Information System (INIS)

    Takahashi, Kayo; Bergstroem, Mats; Fraendberg, Pernilla; Vesstroem, Eva-Lotta; Watanabe, Yasuyoshi; Langstroem, Bengt

    2006-01-01

    Aromatase is an enzyme that converts androgens to estrogens and may play a role in mood and mental status. The aim of this study was to demonstrate that brain aromatase distribution could be evaluated with a novel positron emission tomography (PET) tracer [ 11 C]vorozole. Vorozole is a nonsteroidal aromatase inhibitor that reversibly binds to the heme domain of aromatase. In vitro experiments in rat brain, using frozen section autoradiography, illustrated specific binding in the medial amygdala (MA), the bed nucleus of stria terminalis (BST) and the preoptic area (POA) of male rat brain. Specific binding in female rat brain was found in the MA and the BST; however, the signals were lower than those of males. The K d of [ 11 C]vorozole binding to aromatase in MA was determined to be 0.60±0.06 nM by Scatchard plot analysis using homogenates. An in vivo PET study in female rhesus monkey brain demonstrated the uptake of [ 11 C]vorozole in the amygdala, where the uptake was blocked by the presence of excess amounts of unlabeled vorozole. Thus, this tracer has a high affinity for brain aromatase and could have a potential for in vivo aromatase imaging. This technique might enable the investigation of human brain aromatase in healthy and diseased persons

  9. Distribution of neurotensin receptors in the primate hippocampal region: a quantitative autoradiographic study in the monkey and the postmortem human brain

    International Nuclear Information System (INIS)

    Kohler, Christer; Radesater, A.; Chan-Palay, V.

    1987-01-01

    The distribution of [ 3 H]neurotensin ([ 3 H]NT) binding sites in the monkey and the postmortem human brain was studied by using quantitative in vitro receptor autoradiography. Biochemical experiments carried out on tissue sections of the monkey hippocampus showed that the binding of [ 3 H]NT was saturable, reversible and of high specificity. The hippocampal [ 3 H]NT binding was displaced by fragment NT 8-13 but not fragment NT 1-8 of the peptide. The anatomical analysis showed a highly heterogeneous distribution of [ 3 H]NT binding sites within both the monkey and the human hippocampal region. In both species the highest density of [ 3 H]NT binding sites was found in the presubiculum (rank order of binding density: layer 2>6>1>3, 4, 5 in both monkey and man) and the entorhinal area (monkey: layer 4>6>5>1>2>3; human: layer 1=2>5>3). The subiculum and Ammon's horn were relatively poor in [ 3 H]NT binding sites in both species. In the area dentata the highest density of [ 3 H]NT binding sites was found in the hilar region. (author)

  10. Attenuating Nicotine Reinforcement and Relapse by Enhancing Endogenous Brain Levels of Kynurenic Acid in Rats and Squirrel Monkeys.

    Science.gov (United States)

    Secci, Maria E; Auber, Alessia; Panlilio, Leigh V; Redhi, Godfrey H; Thorndike, Eric B; Schindler, Charles W; Schwarcz, Robert; Goldberg, Steven R; Justinova, Zuzana

    2017-07-01

    The currently available antismoking medications have limited efficacy and often fail to prevent relapse. Thus, there is a pressing need for newer, more effective treatment strategies. Recently, we demonstrated that enhancing endogenous levels of kynurenic acid (KYNA, a neuroinhibitory product of tryptophan metabolism) counteracts the rewarding effects of cannabinoids by acting as a negative allosteric modulator of α7 nicotinic receptors (α7nAChRs). As the effects of KYNA on cannabinoid reward involve nicotinic receptors, in the present study we used rat and squirrel monkey models of reward and relapse to examine the possibility that enhancing KYNA can counteract the effects of nicotine. To assess specificity, we also examined models of cocaine reward and relapse in monkeys. KYNA levels were enhanced by administering the kynurenine 3-monooxygenase (KMO) inhibitor, Ro 61-8048. Treatment with Ro 61-8048 decreased nicotine self-administration in rats and monkeys, but did not affect cocaine self-administration. In rats, Ro 61-8048 reduced the ability of nicotine to induce dopamine release in the nucleus accumbens shell, a brain area believed to underlie nicotine reward. Perhaps most importantly, Ro 61-8048 prevented relapse-like behavior when abstinent rats or monkeys were reexposed to nicotine and/or cues that had previously been associated with nicotine. Ro 61-8048 was also effective in monkey models of cocaine relapse. All of these effects of Ro 61-8048 in monkeys, but not in rats, were reversed by pretreatment with a positive allosteric modulator of α7nAChRs. These findings suggest that KMO inhibition may be a promising new approach for the treatment of nicotine addiction.

  11. Potential Adverse Effects of Prolonged Sevoflurane Exposure on Developing Monkey Brain: From Abnormal Lipid Metabolism to Neuronal Damage.

    Science.gov (United States)

    Liu, Fang; Rainosek, Shuo W; Frisch-Daiello, Jessica L; Patterson, Tucker A; Paule, Merle G; Slikker, William; Wang, Cheng; Han, Xianlin

    2015-10-01

    Sevoflurane is a volatile anesthetic that has been widely used in general anesthesia, yet its safety in pediatric use is a public concern. This study sought to evaluate whether prolonged exposure of infant monkeys to a clinically relevant concentration of sevoflurane is associated with any adverse effects on the developing brain. Infant monkeys were exposed to 2.5% sevoflurane for 9 h, and frontal cortical tissues were harvested for DNA microarray, lipidomics, Luminex protein, and histological assays. DNA microarray analysis showed that sevoflurane exposure resulted in a broad identification of differentially expressed genes (DEGs) in the monkey brain. In general, these genes were associated with nervous system development, function, and neural cell viability. Notably, a number of DEGs were closely related to lipid metabolism. Lipidomic analysis demonstrated that critical lipid components, (eg, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol) were significantly downregulated by prolonged exposure of sevoflurane. Luminex protein analysis indicated abnormal levels of cytokines in sevoflurane-exposed brains. Consistently, Fluoro-Jade C staining revealed more degenerating neurons after sevoflurane exposure. These data demonstrate that a clinically relevant concentration of sevoflurane (2.5%) is capable of inducing and maintaining an effective surgical plane of anesthesia in the developing nonhuman primate and that a prolonged exposure of 9 h resulted in profound changes in gene expression, cytokine levels, lipid metabolism, and subsequently, neuronal damage. Generally, sevoflurane-induced neuronal damage was also associated with changes in lipid content, composition, or both; and specific lipid changes could provide insights into the molecular mechanism(s) underlying anesthetic-induced neurotoxicity and may be sensitive biomarkers for the early detection of anesthetic-induced neuronal damage. Published by Oxford University Press on behalf of the

  12. "Zeroing" in on mathematics in the monkey brain.

    Science.gov (United States)

    Beran, Michael J

    2016-03-01

    A new study documented that monkeys showed selective neuronal responding to the concept of zero during a numerical task, and that there were two distinct classes of neurons that coded the absence of stimuli either through a discrete activation pattern (zero or not zero) or a continuous one for which zero was integrated with other numerosities in the relative rate of activity. These data indicate that monkeys, like humans, have a concept of zero that is part of their analog number line but that also may have unique properties compared to other numerosities.

  13. Hypothalamic-Pituitary-Adrenal Axis Physiology and Cognitive Control of Behavior in Stress Inoculated Monkeys

    Science.gov (United States)

    Parker, Karen J.; Buckmaster, Christine L.; Lindley, Steven E.; Schatzberg, Alan F.; Lyons, David M.

    2012-01-01

    Monkeys exposed to stress inoculation protocols early in life subsequently exhibit diminished neurobiological responses to moderate psychological stressors and enhanced cognitive control of behavior during juvenile development compared to non-inoculated monkeys. The present experiments extended these findings and revealed that stress inoculated…

  14. Epigenetics and brain evolution.

    Science.gov (United States)

    Keverne, Eric B

    2011-04-01

    Fundamental aspects of mammalian brain evolution occurred in the context of viviparity and placentation brought about by the epigenetic regulation of imprinted genes. Since the fetal placenta hormonally primes the maternal brain, two genomes in one individual are transgenerationally co-adapted to ensure maternal care and nurturing. Advanced aspects of neocortical brain evolution has shown very few genetic changes between monkeys and humans. Although these lineages diverged at approximately the same time as the rat and mouse (20 million years ago), synonymous sequence divergence between the rat and mouse is double that when comparing monkey with human sequences. Paradoxically, encephalization of rat and mouse are remarkably similar, while comparison of the human and monkey shows the human cortex to be three times the size of the monkey. This suggests an element of genetic stability between the brains of monkey and man with a greater emphasis on epigenetics providing adaptable variability.

  15. Ketamine changes the local resting-state functional properties of anesthetized-monkey brain.

    Science.gov (United States)

    Rao, Jia-Sheng; Liu, Zuxiang; Zhao, Can; Wei, Rui-Han; Zhao, Wen; Tian, Peng-Yu; Zhou, Xia; Yang, Zhao-Yang; Li, Xiao-Guang

    2017-11-01

    Ketamine is a well-known anesthetic. 'Recreational' use of ketamine common induces psychosis-like symptoms and cognitive impairments. The acute and chronic effects of ketamine on relevant brain circuits have been studied, but the effects of single-dose ketamine administration on the local resting-state functional properties of the brain remain unknown. In this study, we aimed to assess the effects of single-dose ketamine administration on the brain local intrinsic properties. We used resting-state functional magnetic resonance imaging (rs-fMRI) to explore the ketamine-induced alterations of brain intrinsic properties. Seven adult rhesus monkeys were imaged with rs-fMRI to examine the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) in the brain before and after ketamine injection. Paired comparisons were used to detect the significantly altered regions. Results showed that the fALFF of the prefrontal cortex (p=0.046), caudate nucleus (left side, p=0.018; right side, p=0.025), and putamen (p=0.020) in post-injection stage significantly increased compared with those in pre-injection period. The ReHo of nucleus accumbens (p=0.049), caudate nucleus (p=0.037), and hippocampus (p=0.025) increased after ketamine injection, but that of prefrontal cortex decreased (pketamine administration can change the regional intensity and synchronism of brain activity, thereby providing evidence of ketamine-induced abnormal resting-state functional properties in primates. This evidence may help further elucidate the effects of ketamine on the cerebral resting status. Copyright © 2017. Published by Elsevier Inc.

  16. Locomotor recovery after spinal cord hemisection/contusion injures in bonnet monkeys: footprint testing--a minireview.

    Science.gov (United States)

    Rangasamy, Suresh Babu

    2013-07-01

    Spinal cord injuries usually produce loss or impairment of sensory, motor and reflex function below the level of damage. In the absence of functional regeneration or manipulations that promote regeneration, spontaneous improvements in motor functions occur due to the activation of multiple compensatory mechanisms in animals and humans following the partial spinal cord injury. Many studies were performed on quantitative evaluation of locomotor recovery after induced spinal cord injury in animals using behavioral tests and scoring techniques. Although few studies on rodents have led to clinical trials, it would appear imperative to use nonhuman primates such as macaque monkeys in order to relate the research outcomes to recovery of functions in humans. In this review, we will discuss some of our research evidences concerning the degree of spontaneous recovery in bipedal locomotor functions of bonnet monkeys that underwent spinal cord hemisection/contusion lesions. To our knowledge, this is the first report to discuss on the extent of spontaneous recovery in bipedal locomotion of macaque monkeys through the application of footprint analyzing technique. In addition, the results obtained were compared with the published data on recovery of quadrupedal locomotion of spinally injured rodents. We propose that the mechanisms underlying spontaneous recovery of functions in spinal cord lesioned monkeys may be correlated to the mature function of spinal pattern generator for locomotion under the impact of residual descending and afferent connections. Moreover, based on analysis of motor functions observed in locomotion in these subjected monkeys, we understand that spinal automatism and development of responses by afferent stimuli from outside the cord could possibly contribute to recovery of paralyzed hindlimbs. This report also emphasizes the functional contribution of progressive strengthening of undamaged nerve fibers through a collateral sprouts/synaptic plasticity formed

  17. Silent communication: toward using brain signals.

    Science.gov (United States)

    Pei, Xiaomei; Hill, Jeremy; Schalk, Gerwin

    2012-01-01

    From the 1980s movie Firefox to the more recent Avatar, popular science fiction has speculated about the possibility of a persons thoughts being read directly from his or her brain. Such braincomputer interfaces (BCIs) might allow people who are paralyzed to communicate with and control their environment, and there might also be applications in military situations wherever silent user-to-user communication is desirable. Previous studies have shown that BCI systems can use brain signals related to movements and movement imagery or attention-based character selection. Although these systems have successfully demonstrated the possibility to control devices using brain function, directly inferring which word a person intends to communicate has been elusive. A BCI using imagined speech might provide such a practical, intuitive device. Toward this goal, our studies to date addressed two scientific questions: (1) Can brain signals accurately characterize different aspects of speech? (2) Is it possible to predict spoken or imagined words or their components using brain signals?

  18. Post-encoding control of working memory enhances processing of relevant information in rhesus monkeys (Macaca mulatta).

    Science.gov (United States)

    Brady, Ryan J; Hampton, Robert R

    2018-06-01

    Working memory is a system by which a limited amount of information can be kept available for processing after the cessation of sensory input. Because working memory resources are limited, it is adaptive to focus processing on the most relevant information. We used a retro-cue paradigm to determine the extent to which monkey working memory possesses control mechanisms that focus processing on the most relevant representations. Monkeys saw a sample array of images, and shortly after the array disappeared, they were visually cued to a location that had been occupied by one of the sample images. The cue indicated which image should be remembered for the upcoming recognition test. By determining whether the monkeys were more accurate and quicker to respond to cued images compared to un-cued images, we tested the hypothesis that monkey working memory focuses processing on relevant information. We found a memory benefit for the cued image in terms of accuracy and retrieval speed with a memory load of two images. With a memory load of three images, we found a benefit in retrieval speed but only after shortening the onset latency of the retro-cue. Our results demonstrate previously unknown flexibility in the cognitive control of memory in monkeys, suggesting that control mechanisms in working memory likely evolved in a common ancestor of humans and monkeys more than 32 million years ago. Future work should be aimed at understanding the interaction between memory load and the ability to control memory resources, and the role of working memory control in generating differences in cognitive capacity among primates. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Cerebral Anatomy of the Spider Monkey Ateles Geoffroyi Studied Using Magnetic Resonance Imaging. First Report: a Comparative Study with the Human Brain Homo Sapiens

    OpenAIRE

    Chico-Ponce de León, Fernando; Platas-Neri, Diana; Muñoz-Delgado, Jairo; Santillán-Doherty, Ana María; Arenas-Rosas, Rita; Trejo, David; Conde, Rubén; Ojeda-Flores, Rafael; Campos-Romo, Aurelio; Castro-Sierra, Eduardo; Cervantes, Juan José; Braun, Marc

    2009-01-01

    The objective of the present qualitative study was to analyze the morphological aspects of the inner cerebral anatomy of two species of primates, using magnetic resonance images (MRI): spider monkey (A. geoffroyi) and human (H. sapiens), on the basis of a comparative study of the cerebral structures of the two species, focusing upon the brain of the spider monkey and, primarily, its limbic system. In spite of being an endemic Western hemisphere species, a fact which is by its own right intere...

  20. PET measurement of FK506 concentration in a monkey model of stroke

    International Nuclear Information System (INIS)

    Murakami, Yoshihiro; Takamatsu, Hiroyuki; Noda, Akihiro; Osoda, Kazuhiko; Nishimura, Shintaro

    2007-01-01

    Introduction: The immunosuppressive agent FK506 (tacrolimus) has neuroprotective properties in an experimental model of cerebral ischemia. To improve the accuracy of clinical studies in acute stroke, a clinical dose setting should be based on the brain concentration, but not on the blood concentration of agents in humans. We have already established a measurement method using PET for FK506 concentration in the normal monkey brain, which could be applicable for human study; however, under ischemic conditions, in this study, we aimed to examine the brain concentration of FK506 in a monkey model of stroke. Methods: Studies were performed on six male cynomolgus monkeys (Macaca fascicularis) and a middle cerebral artery (MCA) occlusion model was used. Regional cerebral blood flow (rCBF) was measured by an intravenous injection of [ 15 O]H 2 O 165 min after MCA occlusion. FK506 (0.1 mg/kg) containing [ 11 C]FK506 was intravenously injected into the monkeys 180 min after MCA occlusion, and dynamic PET images were acquired for 30 min after administration. FK506 concentrations in the brain were calculated in moles per liter (M) units using the specific activity of injected FK506. Results: MCA occlusion produced ischemia, confirmed by rCBF measurement before the administration of [ 11 C]FK506. Fifteen minutes after FK506 (0.1 mg/kg) administration, the concentrations in the contralateral and ipsilateral cortex were 22.4±6.4 and 19.7±4.0 ng/g, respectively. Conclusion: We successfully measured the brain concentration of FK506 in a monkey model of stroke. The difference between the contralateral and ipsilateral concentrations of FK506 was not significant. This characteristic that FK506 readily penetrates ischemic tissue as well as normal tissue might explain the neuroprotective effect of FK506 in the ischemic brain and is suitable for the treatment of stroke patients

  1. Beyond intuitive anthropomorphic control: recent achievements using brain computer interface technologies

    Science.gov (United States)

    Pohlmeyer, Eric A.; Fifer, Matthew; Rich, Matthew; Pino, Johnathan; Wester, Brock; Johannes, Matthew; Dohopolski, Chris; Helder, John; D'Angelo, Denise; Beaty, James; Bensmaia, Sliman; McLoughlin, Michael; Tenore, Francesco

    2017-05-01

    Brain-computer interface (BCI) research has progressed rapidly, with BCIs shifting from animal tests to human demonstrations of controlling computer cursors and even advanced prosthetic limbs, the latter having been the goal of the Revolutionizing Prosthetics (RP) program. These achievements now include direct electrical intracortical microstimulation (ICMS) of the brain to provide human BCI users feedback information from the sensors of prosthetic limbs. These successes raise the question of how well people would be able to use BCIs to interact with systems that are not based directly on the body (e.g., prosthetic arms), and how well BCI users could interpret ICMS information from such devices. If paralyzed individuals could use BCIs to effectively interact with such non-anthropomorphic systems, it would offer them numerous new opportunities to control novel assistive devices. Here we explore how well a participant with tetraplegia can detect infrared (IR) sources in the environment using a prosthetic arm mounted camera that encodes IR information via ICMS. We also investigate how well a BCI user could transition from controlling a BCI based on prosthetic arm movements to controlling a flight simulator, a system with different physical dynamics than the arm. In that test, the BCI participant used environmental information encoded via ICMS to identify which of several upcoming flight routes was the best option. For both tasks, the BCI user was able to quickly learn how to interpret the ICMSprovided information to achieve the task goals.

  2. Binding kinetics of 11C-N-methyl piperidyl benzilate (11C-NMPB) in a rhesus monkey brain using the cerebellum as a reference region

    International Nuclear Information System (INIS)

    Itoh, Takashi; Tanaka, Masayasu; Suzuki, Kasutoshi; Kobayashi, Kaoru; Inoue, Osamu

    2005-01-01

    The binding kinetics of' 11 C-N-methyl piperidyl benzilate ( 11 C-NMPB) in rhesus monkey brain were studied using animal positron emission tomography (PET) (SHR2000). This study is intended to assess the validity of the method using the cerebellum as a reference region, and to evaluate the effects of anesthesia on 11 C -NMPB binding. Two monkeys, anesthetized with ketamine, received intravenous 11 C-NMPB alone (370-760 MBq, 11 C-NMPB accumulated densely in the striatum and cerebral cortex with time. In contrast, the tracer accumulation significantly decreased with increased doses of nonradioactive NMPB. In the cerebellum, on the other hand, the accumulation of 11 C-NMPB remained low and the tracer was slowly eliminated from the brain following the injection. 11 C-NMPB binding in the cerebellum was barely affected by the increased dose of nonradioactive NMPB. We thus concluded that the specific 11 C-NMPB binding was negligible in the cerebellum, and performed simplified evaluation of 11 C-NMPB binding in each brain region by a graphical method using the cerebellum as a reference region. PET was conducted 26 times, in total both in ketamine-anesthetized and awake monkeys (n=3 each). Measurements of 11 C-NMPB binding showed good run-to-run reproducibility within individual animals. When 11 C-NMPB binding was compared between ketamine-treated and awake animals, a significant increase in 11 C-NMPB binding was observed in the striatum but not in other brain regions of ketamine-treated animals. (author)

  3. Imaging of aromatase distribution in rat and rhesus monkey brains with [{sup 11}C]vorozole

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Kayo [Division of Pharmacology, Department of Neuroscience, Uppsala University, Uppsala SE-75124 (Sweden); Uppsala Imanet, Uppsala SE-75109 (Sweden)]. E-mail: kayo.takahashi@uppsala.imanet.se; Bergstroem, Mats [Uppsala Imanet, Uppsala SE-75109 (Sweden); Department of Pharmaceutical Biosciences, Uppsala University, Uppsala SE-75124 (Sweden); Fraendberg, Pernilla [Uppsala Imanet, Uppsala SE-75109 (Sweden); Vesstroem, Eva-Lotta [Uppsala Imanet, Uppsala SE-75109 (Sweden); Watanabe, Yasuyoshi [Department of Physiology, Osaka City University Graduate School of Medicine, Osaka 545-8585 (Japan); Langstroem, Bengt [Uppsala Imanet, Uppsala SE-75109 (Sweden)

    2006-07-15

    Aromatase is an enzyme that converts androgens to estrogens and may play a role in mood and mental status. The aim of this study was to demonstrate that brain aromatase distribution could be evaluated with a novel positron emission tomography (PET) tracer [{sup 11}C]vorozole. Vorozole is a nonsteroidal aromatase inhibitor that reversibly binds to the heme domain of aromatase. In vitro experiments in rat brain, using frozen section autoradiography, illustrated specific binding in the medial amygdala (MA), the bed nucleus of stria terminalis (BST) and the preoptic area (POA) of male rat brain. Specific binding in female rat brain was found in the MA and the BST; however, the signals were lower than those of males. The K {sub d} of [{sup 11}C]vorozole binding to aromatase in MA was determined to be 0.60{+-}0.06 nM by Scatchard plot analysis using homogenates. An in vivo PET study in female rhesus monkey brain demonstrated the uptake of [{sup 11}C]vorozole in the amygdala, where the uptake was blocked by the presence of excess amounts of unlabeled vorozole. Thus, this tracer has a high affinity for brain aromatase and could have a potential for in vivo aromatase imaging. This technique might enable the investigation of human brain aromatase in healthy and diseased persons.

  4. Different sensitivities to competitive inhibition of benzodiazepine receptor binding of {sup 11}C-iomazenil and {sup 11}C-flumazenil in rhesus monkey brain

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Osamu; Hosoi, Rie; Kobayashi, Kaoru [Osaka Univ., Suita (Japan). Medical School; Itoh, Takashi; Gee, A.; Suzuki, Kazutoshi

    2001-04-01

    The in vivo binding kinetics of {sup 11}C-iomazenil were compared with those of {sup 11}C-flumazenil binding in rhesus monkey brain. The monkey was anesthetized with ketamine and intravenously injected with either {sup 11}C-iomazenil or {sup 11}C-flumazenil in combination with the coadministration of different doses of non-radioactive flumazenil (0, 5 and 20 {mu}g/kg). The regional distribution of {sup 11}C-iomazenil in the brain was similar to that of {sup 11}C-flumazenil, but the sensitivity of {sup 11}C-iomazenil binding to competitive inhibition by non-radioactive flumazenil was much less than that of {sup 11}C-flumazenil binding. A significant reduction in {sup 11}C-flumazenil binding in the cerebral cortex was observed with 20 {mu}g/kg of flumazenil, whereas a relatively smaller inhibition of {sup 11}C-iomazenil binding in the same region was observed with the same dose of flumazenil. These results suggest that {sup 11}C-flumazenil may be a superior radiotracer for estimating benzodiazepine receptor occupancy in the intact brain. (author)

  5. Monkey alcohol tissue research resource: banking tissues for alcohol research.

    Science.gov (United States)

    Daunais, James B; Davenport, April T; Helms, Christa M; Gonzales, Steven W; Hemby, Scott E; Friedman, David P; Farro, Jonathan P; Baker, Erich J; Grant, Kathleen A

    2014-07-01

    An estimated 18 million adults in the United States meet the clinical criteria for diagnosis of alcohol abuse or alcoholism, a disorder ranked as the third leading cause of preventable death. In addition to brain pathology, heavy alcohol consumption is comorbid with damage to major organs including heart, lungs, liver, pancreas, and kidneys. Much of what is known about risk for and consequences of heavy consumption derive from rodent or retrospective human studies. The neurobiological effects of chronic intake in rodent studies may not easily translate to humans due to key differences in brain structure and organization between species, including a lack of higher-order cognitive functions, and differences in underlying prefrontal cortical neural structures that characterize the primate brain. Further, rodents do not voluntarily consume large quantities of ethanol (EtOH) and they metabolize it more rapidly than primates. The basis of the Monkey Alcohol Tissue Research Resource (MATRR) is that nonhuman primates, specifically monkeys, show a range of drinking excessive amounts of alcohol (>3.0 g/kg or a 12 drink equivalent per day) over long periods of time (12 to 30 months) with concomitant pathological changes in endocrine, hepatic, and central nervous system (CNS) processes. The patterns and range of alcohol intake that monkeys voluntarily consume parallel what is observed in humans with alcohol use disorders and the longitudinal experimental design spans stages of drinking from the EtOH-naïve state to early exposure through chronic abuse. Age- and sex-matched control animals self-administer an isocaloric solution under identical operant procedures. The MATRR is a unique postmortem tissue bank that provides CNS and peripheral tissues, and associated bioinformatics from monkeys that self-administer EtOH using a standardized experimental paradigm to the broader alcohol research community. This resource provides a translational platform from which we can better

  6. Cholinergic Modulation of Cortical Microcircuits Is Layer-Specific: Evidence from Rodent, Monkey and Human Brain

    Directory of Open Access Journals (Sweden)

    Joshua Obermayer

    2017-12-01

    Full Text Available Acetylcholine (ACh signaling shapes neuronal circuit development and underlies specific aspects of cognitive functions and behaviors, including attention, learning, memory and motivation. During behavior, activation of muscarinic and nicotinic acetylcholine receptors (mAChRs and nAChRs by ACh alters the activation state of neurons, and neuronal circuits most likely process information differently with elevated levels of ACh. In several brain regions, ACh has been shown to alter synaptic strength as well. By changing the rules for synaptic plasticity, ACh can have prolonged effects on and rearrange connectivity between neurons that outlasts its presence. From recent discoveries in the mouse, rat, monkey and human brain, a picture emerges in which the basal forebrain (BF cholinergic system targets the neocortex with much more spatial and temporal detail than previously considered. Fast cholinergic synapses acting on a millisecond time scale are abundant in the mammalian cerebral cortex, and provide BF cholinergic neurons with the possibility to rapidly alter information flow in cortical microcircuits. Finally, recent studies have outlined novel mechanisms of how cholinergic projections from the BF affect synaptic strength in several brain areas of the rodent brain, with behavioral consequences. This review highlights these exciting developments and discusses how these findings translate to human brain circuitries.

  7. Comment on "Monkey vocal tracts are speech-ready".

    Science.gov (United States)

    Lieberman, Philip

    2017-07-01

    Monkey vocal tracts are capable of producing monkey speech, not the full range of articulate human speech. The evolution of human speech entailed both anatomy and brains. Fitch, de Boer, Mathur, and Ghazanfar in Science Advances claim that "monkey vocal tracts are speech-ready," and conclude that "…the evolution of human speech capabilities required neural change rather than modifications of vocal anatomy." Neither premise is consistent either with the data presented and the conclusions reached by de Boer and Fitch themselves in their own published papers on the role of anatomy in the evolution of human speech or with the body of independent studies published since the 1950s.

  8. Communication and control by listening: towards optimal design of a two-class auditory streaming brain-computer interface

    Directory of Open Access Journals (Sweden)

    N. Jeremy Hill

    2012-12-01

    Full Text Available Most brain-computer interface (BCI systems require users to modulate brain signals in response to visual stimuli. Thus, they may not be useful to people with limited vision, such as those with severe paralysis. One important approach for overcoming this issue is auditory streaming, an approach whereby a BCI system is driven by shifts of attention between two dichotically presented auditory stimulus streams. Motivated by the long-term goal of translating such a system into a reliable, simple yes-no interface for clinical usage, we aim to answer two main questions. First, we asked which of two previously-published variants provides superior performance: a fixed-phase (FP design in which the streams have equal period and opposite phase, or a drifting-phase (DP design where the periods are unequal. We found FP to be superior to DP (p = 0.002: average performance levels were 80% and 72% correct, respectively. We were also able to show, in a pilot with one subject, that auditory streaming can support continuous control and neurofeedback applications: by shifting attention between ongoing left and right auditory streams, the subject was able to control the position of a paddle in a computer game. Second, we examined whether the system is dependent on eye movements, since it is known that eye movements and auditory attention may influence each other, and any dependence on the ability to move one’s eyes would be a barrier to translation to paralyzed users. We discovered that, despite instructions, some subjects did make eye movements that were indicative of the direction of attention. However, there was no correlation, across subjects, between the reliability of the eye movement signal and the reliability of the BCI system, indicating that our system was configured to work independently of eye movement. Together, these findings are an encouraging step forward toward BCIs that provide practical communication and control options for the most severely

  9. Communication and control by listening: toward optimal design of a two-class auditory streaming brain-computer interface.

    Science.gov (United States)

    Hill, N Jeremy; Moinuddin, Aisha; Häuser, Ann-Katrin; Kienzle, Stephan; Schalk, Gerwin

    2012-01-01

    Most brain-computer interface (BCI) systems require users to modulate brain signals in response to visual stimuli. Thus, they may not be useful to people with limited vision, such as those with severe paralysis. One important approach for overcoming this issue is auditory streaming, an approach whereby a BCI system is driven by shifts of attention between two simultaneously presented auditory stimulus streams. Motivated by the long-term goal of translating such a system into a reliable, simple yes-no interface for clinical usage, we aim to answer two main questions. First, we asked which of two previously published variants provides superior performance: a fixed-phase (FP) design in which the streams have equal period and opposite phase, or a drifting-phase (DP) design where the periods are unequal. We found FP to be superior to DP (p = 0.002): average performance levels were 80 and 72% correct, respectively. We were also able to show, in a pilot with one subject, that auditory streaming can support continuous control and neurofeedback applications: by shifting attention between ongoing left and right auditory streams, the subject was able to control the position of a paddle in a computer game. Second, we examined whether the system is dependent on eye movements, since it is known that eye movements and auditory attention may influence each other, and any dependence on the ability to move one's eyes would be a barrier to translation to paralyzed users. We discovered that, despite instructions, some subjects did make eye movements that were indicative of the direction of attention. However, there was no correlation, across subjects, between the reliability of the eye movement signal and the reliability of the BCI system, indicating that our system was configured to work independently of eye movement. Together, these findings are an encouraging step forward toward BCIs that provide practical communication and control options for the most severely paralyzed users.

  10. The Effect of Extremely Low Frequency Electromagnetic Fields on Visual Learning & Memory and Anatomical Structures of the Brain in Male Rhesus Monkeys

    Directory of Open Access Journals (Sweden)

    Elahe Tekieh

    2018-04-01

    Full Text Available Background: Humans in modern societies expose to substantially elevated levels of electromagnetic field (EMF emissions with different frequencies.The neurobiological effects of EMF have been the subject of debate and intensive research over the past few decades. Therefore, we evaluated the effects of EMF on visual learning and anatomical dimensions of the hippocampus and the prefrontal area (PFA in male Rhesus monkeys. Materials and Methods:In this study, four rhesus monkeys were irradiated by 0.7 microtesla ELF-EMF either at 5 or 30 Hz, 4 h a day, for 30 days. Alterations in visual learning and memory were assessed before and after irradiation phase by using a box designed that cchallenging animals for gaining rewards Also, the monkeys’ brains were scanned by using MRI technique one week before and one week after irradiation. The monkeys were anesthetized by intramuscular injection of ketamine hydrochloride (10–20 mg/kg and xylazine (0.2–0.4 mg/kg, and scanned with a 3-Tesla Magnetom, in axial, sagittal, and coronal planes using T2 weight­ed protocol with a slice thickness of 3 mm. The anatomical changes of hippocampus and the prefrontal area (PFA was measured by volumetric study. Results: Electromagnetic field exposure at a frequency of 30 Hz reduced the number of correct responses in the learning process and delayed memory formation in the two tested monkeys. While, ELF-EMF at 5 Hz had no effect on the visual learning and memory changes. No anatomical changes were found in the prefrontal area and the hippocampus at both frequencies. Conclusion: ELF-EMF irradiation at 30 Hz adversely affected visual learning and memory, pprobably through these changes apply through effects on other factors except changes in brain structure and anatomy.

  11. Naturally transmitted herpesvirus papio-2 infection in a black and white colobus monkey.

    Science.gov (United States)

    Troan, Brigid V; Perelygina, Ludmila; Patrusheva, Irina; Wettere, Arnaud J van; Hilliard, Julia K; Loomis, Michael R; Voe, Ryan S De

    2007-12-15

    A 6.5-year-old female eastern black and white colobus monkey (Colobus guereza) was evaluated after acute onset of ataxia and inappetence. The monkey was ataxic and lethargic, but no other abnormalities were detected via physical examination, radiography, or clinicopathologic analyses. During the next 2 days, the monkey's clinical condition deteriorated, and its WBC count decreased dramatically. Cytologic examination of a CSF sample revealed marked lymphohistiocytic inflammation. Despite supportive care, the monkey became apneic; after 20 hours of mechanical ventilation, fatal cardiac arrest occurred. At necropsy, numerous petechiae were detected within the white matter tracts of the brain; microscopic lesions of multifocal necrosis and hemorrhage with intranuclear inclusions identified in the brain and adrenal glands were consistent with an acute herpesvirus infection. A specific diagnosis of herpesvirus papio-2 (HVP-2) infection was made on the basis of results of serologic testing; PCR assay of tissue specimens; live virus isolation from the lungs; and immunohistochemical identification of the virus within brain, spinal cord, and adrenal gland lesions. Via phylogenetic tree analysis, the colobus HVP-2 isolate was grouped with neuroinvasive strains of the virus. The virus was most likely transmitted to the colobus monkey through toys shared with a nearby colony of baboons (the natural host of HVP-2). To the authors' knowledge, this is the first reported case of natural transmission of HVP-2 to a nonhost species. Infection with HVP-2 should be a differential diagnosis for acute encephalopathy in primate monkeys and humans, particularly following exposure to baboons.

  12. Neurons in the brain of the male cynomolgus monkey accumulate 3H-medroxyprogesterone acetate (MPA)

    International Nuclear Information System (INIS)

    Michael, R.P.; Bonsall, R.W.; Rees, H.D.

    1986-01-01

    MPA is a synthetic progestin with androgen-depleting activity. It is used clinically to reduce sexual motivation and aggression in male sex offenders. The mechanisms for its behavioral effects are not known. The authors used steroid autoradiography to help identify sites where MPA may act in the brain of male primates. Twenty-four hours after castration, two adult male cynomolgus macaques, weighing 4.9 and 6.6 kg, were administered 5 mCi 3 H-MPA (NEN, 47.7 Ci/mmol) i.v., and were killed 1 h later. Left sides of the brains and samples of pituitary glands were frozen and 4-micron sections were cut and processed for thaw-mount autoradiography. Radioactivity was concentrated in the nuclei of many neutrons in the ventromedial hypothalamic nucleus (n.), arcuate n., medial preoptic n., and anterior hypothalamic area. Virtually no labeled cells were seen in the bed n. of stria terminalis, lateral septal n., amygdala, or pituitary gland. Right sides of the brains were analyzed by HPLC which demonstrated that 98% of the radioactivity in cell nuclei from the hypothalamus was in the form of unmetabolized 3 H-MPA. The distribution of labelling in the brain following 3 H-MPA administration resembled that previously seen following 3 H-ORG 2058 in female cynomolgus monkeys. These data indicate that MPA has a circumscribed localization in the brain

  13. Postfatigue potentiation of the paralyzed soleus muscle: evidence for adaptation with long-term electrical stimulation training

    OpenAIRE

    Shields, Richard K.; Dudley-Javoroski, Shauna; Littmann, Andrew E.

    2006-01-01

    Understanding the torque output behavior of paralyzed muscle has important implications for the use of functional neuromuscular electrical stimulation systems. Postfatigue potentiation is an augmentation of peak muscle torque during repetitive activation after a fatigue protocol. The purposes of this study were 1) to quantify postfatigue potentiation in the acutely and chronically paralyzed soleus and 2) to determine the effect of long-term soleus electrical stimulation training on the potent...

  14. Evaluation of blood--brain barrier permeability changes in rhesus monkeys and man using 82Rb and positron emission tomography

    International Nuclear Information System (INIS)

    Yen, C.K.; Budinger, T.F.

    1981-01-01

    Dynamic positron tomography of the brain with 82 Rb, obtained from a portable generator [ 82 Sr (25 days) -- 82 Rb (76 sec)], provides a means of studying blood-brain barrier (BBB) permeability in physiological and clinical investigations. The BBB in rhesus monkeys was opened unilaterally by intracarotid infusion of 3 M urea. This osmotic barrier opening allowed entry into the brain of intravenously administered rubidium chloride. The BBB opening was demonstrated noninvasively using 82 Rb and positron emission tomography and corroborated by the accumulation of 86 Rb in tissue samples. Positron emission tomography studies can be repeated every 5 min and indicate that dynamic tomography or static imaging can be used to study BBB permeability changes induced by a wide variety of noxious stimuli. Brain tumors in human subjects are readily detected because of the usual BBB permeability disruption in and around the tumors

  15. Pharmacokinetics and safety in rhesus monkeys of a monoclonal antibody-GDNF fusion protein for targeted blood-brain barrier delivery.

    Science.gov (United States)

    Pardridge, William M; Boado, Ruben J

    2009-10-01

    Glial-derived neurotrophic factor (GDNF) is a potential therapy for stroke, Parkinson's disease, or drug addiction. However, GDNF does not cross the blood-brain barrier (BBB). GDNF is re-engineered as a fusion protein with a chimeric monoclonal antibody (MAb) to the human insulin receptor (HIR), which acts as a molecular Trojan horse to deliver the GDNF across the BBB. The pharmacokinetics (PK), toxicology, and safety pharmacology of the HIRMAb-GDNF fusion protein were investigated in Rhesus monkeys. The fusion protein was administered as an intravenous injection at doses up to 50 mg/kg over a 60 h period to 56 Rhesus monkeys. The plasma concentration of the HIRMAb-GDNF fusion protein was measured with a 2-site sandwich ELISA. No adverse events were observed in a 2-week terminal toxicology study, and no neuropathologic changes were observed. The PK analysis showed a linear relationship between plasma AUC and dose, a large systemic volume of distribution, as well as high clearance rates of 8-10 mL/kg/min. A no-observable-adverse-effect level is established in the Rhesus monkey for the acute administration of the HIRMAb-GDNF fusion protein. The fusion protein targeting the insulin receptor has a PK profile similar to a classical small molecule.

  16. Comparing amyloid-β deposition, neuroinflammation, glucose metabolism, and mitochondrial complex I activity in brain: a PET study in aged monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Tsukada, Hideo; Nishiyama, Shingo; Ohba, Hiroyuki; Kanazawa, Masakatsu; Kakiuchi, Takeharu; Harada, Norihiro [Hamamatsu Photonics K.K., Central Research Laboratory, Shizuoka (Japan)

    2014-11-15

    The aim of the present study was to compare amyloid-β (Aβ) deposition, translocator protein (TSPO) activity, regional cerebral metabolic rate of glucose (rCMRglc), and mitochondrial complex I (MC-I) activity in the brain of aged monkeys. PET scans with {sup 11}C-PIB (Aβ), {sup 18}F-BCPP-EF (MC-I), {sup 11}C-DPA-713 (TSPO), and {sup 18}F-FDG (rCMRglc) were performed in aged monkeys (Macaca mulatta) in the conscious state and under isoflurane anaesthesia. {sup 11}C-PIB binding to Aβ and {sup 11}C-DPA-713 binding to TSPO were evaluated in terms of standard uptake values (SUV). The total volume of distribution (V{sub T}) of {sup 18}F-BCPP-EF and rCMRglc with {sup 18}F-FDG were calculated using arterial blood sampling. Isoflurane did not affect MC-I activity measured in terms of {sup 18}F-BCPP-EF uptake in living brain. There was a significant negative correlation between {sup 18}F-BCPP-EF binding (V{sub T}) and {sup 11}C-PIB uptake (SUVR), and there was a significant positive correlation between {sup 11}C-DPA-713 uptake (SUV) and {sup 11}C-PIB uptake. In contrast, there was no significant correlation between rCMRglc ratio and {sup 11}C-PIB uptake. {sup 18}F-BCPP-EF could be a potential PET probe for quantitative imaging of impaired MC-I activity that is correlated with Aβ deposition in the living brain. (orig.)

  17. TALEN-based generation of a cynomolgus monkey disease model for human microcephaly

    Science.gov (United States)

    Ke, Qiong; Li, Weiqiang; Lai, Xingqiang; Chen, Hong; Huang, Lihua; Kang, Zhuang; Li, Kai; Ren, Jie; Lin, Xiaofeng; Zheng, Haiqing; Huang, Weijun; Ma, Yunhan; Xu, Dongdong; Chen, Zheng; Song, Xinming; Lin, Xinyi; Zhuang, Min; Wang, Tao; Zhuang, Fengfeng; Xi, Jianzhong; Mao, Frank Fuxiang; Xia, Huimin; Lahn, Bruce T; Zhou, Qi; Yang, Shihua; Xiang, Andy Peng

    2016-01-01

    Gene editing in non-human primates may lead to valuable models for exploring the etiologies and therapeutic strategies of genetically based neurological disorders in humans. However, a monkey model of neurological disorders that closely mimics pathological and behavioral deficits in humans has not yet been successfully generated. Microcephalin 1 (MCPH1) is implicated in the evolution of the human brain, and MCPH1 mutation causes microcephaly accompanied by mental retardation. Here we generated a cynomolgus monkey (Macaca fascicularis) carrying biallelic MCPH1 mutations using transcription activator-like effector nucleases. The monkey recapitulated most of the important clinical features observed in patients, including marked reductions in head circumference, premature chromosome condensation (PCC), hypoplasia of the corpus callosum and upper limb spasticity. Moreover, overexpression of MCPH1 in mutated dermal fibroblasts rescued the PCC syndrome. This monkey model may help us elucidate the role of MCPH1 in the pathogenesis of human microcephaly and better understand the function of this protein in the evolution of primate brain size. PMID:27502025

  18. A case of polymicrogyria in macaque monkey: impact on anatomy and function of the motor system

    Directory of Open Access Journals (Sweden)

    Rouiller Eric M

    2009-12-01

    Full Text Available Abstract Background Polymicrogyria is a malformation of the cerebral cortex often resulting in epilepsy or mental retardation. It remains unclear whether this pathology affects the structure and function of the corticospinal (CS system. The anatomy and histology of the brain of one macaque monkey exhibiting a spontaneous polymicrogyria (PMG monkey were examined and compared to the brain of normal monkeys. The CS tract was labelled by injecting a neuronal tracer (BDA unilaterally in a region where low intensity electrical microstimulation elicited contralateral hand movements (presumably the primary motor cortex in the PMG monkey. Results The examination of the brain showed a large number of microgyri at macro- and microscopic levels, covering mainly the frontoparietal regions. The layered cortical organization was locally disrupted and the number of SMI-32 stained pyramidal neurons in the cortical layer III of the presumed motor cortex was reduced. We compared the distribution of labelled CS axons in the PMG monkey at spinal cervical level C5. The cumulated length of CS axon arbors in the spinal grey matter was not significantly different in the PMG monkey. In the red nucleus, numerous neurons presented large vesicles. We also assessed its motor performances by comparing its capacity to execute a complex reach and grasp behavioral task. The PMG monkey exhibited an increase of reaction time without any modification of other motor parameters, an observation in line with a normal CS tract organisation. Conclusion In spite of substantial cortical malformations in the frontal and parietal lobes, the PMG monkey exhibits surprisingly normal structure and function of the corticospinal system.

  19. Monkey cortex through fMRI glasses.

    Science.gov (United States)

    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. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Learning to control a brain-machine interface for reaching and grasping by primates.

    Directory of Open Access Journals (Sweden)

    Jose M Carmena

    2003-11-01

    Full Text Available Reaching and grasping in primates depend on the coordination of neural activity in large frontoparietal ensembles. Here we demonstrate that primates can learn to reach and grasp virtual objects by controlling a robot arm through a closed-loop brain-machine interface (BMIc that uses multiple mathematical models to extract several motor parameters (i.e., hand position, velocity, gripping force, and the EMGs of multiple arm muscles from the electrical activity of frontoparietal neuronal ensembles. As single neurons typically contribute to the encoding of several motor parameters, we observed that high BMIc accuracy required recording from large neuronal ensembles. Continuous BMIc operation by monkeys led to significant improvements in both model predictions and behavioral performance. Using visual feedback, monkeys succeeded in producing robot reach-and-grasp movements even when their arms did not move. Learning to operate the BMIc was paralleled by functional reorganization in multiple cortical areas, suggesting that the dynamic properties of the BMIc were incorporated into motor and sensory cortical representations.

  1. Streptococcus oralis cerebral abscess following monkey bite in a 2-month-old infant.

    Science.gov (United States)

    Thiagarajan, Srinivasan; Krishnamurthy, Sriram; Raghavan, Renitha; Mahadevan, Subramanian; Madhugiri, Venkatesh S; Sistla, Sujatha

    2016-05-01

    Although cerebral abscesses caused by animal bites have been reported, they are extremely rare in infants and have not been described following monkey bite. A 55-day-old male infant presented with a multi-loculated Streptococcus oralis cerebral abscess following a monkey bite on the scalp. There was a clinical response to antibiotic therapy and repeated surgical aspiration followed by a ventriculoperitoneal shunt. This is the first report of a patient with a brain abscess following a monkey bite.

  2. Lifetime effects of single-event proton exposures in rhesus monkeys

    International Nuclear Information System (INIS)

    Wood, D.H.; Yochmowitz, M.G.; Salmon, Y.L.

    1986-01-01

    The US School of Aerospace Medicine studies of the lifetime effects of proton irradiation in rhesus monkeys have been conducted. Life-span shortening has been associated with proton energies of 55 MeV and above, as well as with doses greater than 360 rads. Female rhesus monkeys have a higher mortality than males as a result of high incidence of endometriosis in the irradiated animals. A dose ordering effect is apparent. Mortality rates began to accelerate at eight years after doses of 360 to 400 rads; at two years, after 500 to 650 rads; and less than one year, after 800 rads. Malignant tumors accounted for 18% of the deaths in the proton-exposed animals. Endometriosis was the cause of 25% of the deaths in this group. Energy-specific effects were observed. Eight malignant brain tumors occurred in animals exposed to 55-MeV protons and in no other group. Cataract incidence was highest in animals exposed to 32 and 55 MeV. These observations suggest a positive relationship with the Bragg peak energy distribution in the area of the brain and crystalline lens. Glucose tolerance was lowest in the animals exposed to totally penetrating radiation, where the fraction of the surface dose reaching the pancreas was highest. Age-matched control animals have yet to pass their median survival time, and the colony continues to be a valuable source of data on the relationship of total-body radiation to age-related diseases in captive monkeys. 16 refs., 6 figs., 5 tabs

  3. Epidurography with metrizamide in Rhesus monkeys

    International Nuclear Information System (INIS)

    Kido, D.K.; Baker, R.A.; Saubermann, A.; Salem, J.; Schoene, W.C.; Fournier, P.

    1980-01-01

    Epidurography with metrizamide was performed on 9 Rhesus monkeys; physiologic saline was substituted for metrizamide in 3 control monkeys. Metrizamide successfully outlined the epidural space without causing any adverse clinical effects or direct tissue injury. (Auth.)

  4. Perceived control in rhesus monkeys (Macaca mulatta) - Enhanced video-task performance

    Science.gov (United States)

    Washburn, David A.; Hopkins, William D.; Rumbaugh, Duane M.

    1991-01-01

    This investigation was designed to determine whether perceived control effects found in humans extend to rhesus monkeys (Macaca mulatta) tested in a video-task format, using a computer-generated menu program, SELECT. Choosing one of the options in SELECT resulted in presentation of five trials of a corresponding task and subsequent return to the menu. In Experiments 1-3, the animals exhibited stable, meaningful response patterns in this task (i.e., they made choices). In Experiment 4, performance on tasks that were selected by the animals significantly exceeded performance on identical tasks when assigned by the experimenter under comparable conditions (e.g., time of day, order, variety). The reliable and significant advantage for performance on selected tasks, typically found in humans, suggests that rhesus monkeys were able to perceive the availability of choices.

  5. Marmoset monkeys evaluate third-party reciprocity.

    Science.gov (United States)

    Kawai, Nobuyuki; Yasue, Miyuki; Banno, Taku; Ichinohe, Noritaka

    2014-05-01

    Many non-human primates have been observed to reciprocate and to understand reciprocity in one-to-one social exchanges. A recent study demonstrated that capuchin monkeys are sensitive to both third-party reciprocity and violation of reciprocity; however, whether this sensitivity is a function of general intelligence, evidenced by their larger brain size relative to other primates, remains unclear. We hypothesized that highly pro-social primates, even with a relatively smaller brain, would be sensitive to others' reciprocity. Here, we show that common marmosets discriminated between human actors who reciprocated in social exchanges with others and those who did not. Monkeys accepted rewards less frequently from non-reciprocators than they did from reciprocators when the non-reciprocators had retained all food items, but they accepted rewards from both actors equally when they had observed reciprocal exchange between the actors. These results suggest that mechanisms to detect unfair reciprocity in third-party social exchanges do not require domain-general higher cognitive ability based on proportionally larger brains, but rather emerge from the cooperative and pro-social tendencies of species, and thereby suggest this ability evolved in multiple primate lineages. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  6. Somatosensory deficits in monkeys treated with misonidazole

    International Nuclear Information System (INIS)

    Maurissen, J.P.J.; Conroy, P.J.; Passalacqua, W.; Von Burg, R.; Weiss, B.; Sutherland, R.M.

    1981-01-01

    Misonidazole, a hypoxic cell radiosensitizer, can produce peripheral sensory disorders in humans. It has been studied in monkeys with a computer-controlled system for evaluating vibration sensitivity. Monkeys were trained to report when vibration was stimulating the finger tip. Sinusoidal vibrations of several frequencies were presented. Two monkeys were dosed with misonidazole and their vibration sensitivity tested. They received a dose of 3 g/m 2 (about 180 mg/kg) twice weekly over a period of 6 to 10 weeks. An amplitude-frequency detection function was determined for each monkey before and after drug treatment. An analysis of covariance comparing polynomial regressions was performed. A significant difference (p < 0.001) was found between control and experimental curves in both monkeys. Pharmacokinetic data indicated a half-life of the drug in blood of about 4 to 5 hr. The overall half-life for elimination did not increase throughout prolonged treatment with msonidazole. Neither motor nor sensory nerve conduction velocity was reduced after treatment

  7. The serotonin transporter in rhesus monkey brain: comparison of DASB and citalopram binding sites

    International Nuclear Information System (INIS)

    Zeng Zhizhen; Chen, T.-B.; Miller, Patricia J.; Dean, Dennis; Tang, Y.S.; Sur, Cyrille; Williams, David L.

    2006-01-01

    We have characterized the interaction of the serotonin transporter ligand [ 3 H]-N,N-dimethyl-2-(2-amino-4-cyanophenylthio)-benzylamine (DASB) with rhesus monkey brain in vitro using tissue homogenate binding and autoradiographic mapping. [ 3 H]-DASB, a tritiated version of the widely used [ 11 C] positron emission tomography tracer, was found to selectively bind to a single population of sites with high affinity (K d =0.20±0.04 nM). The serotonin transporter density (B max ) obtained for rhesus frontal cortex was found to be 66±8 fmol/mg protein using [ 3 H]-DASB, similar to the B max value obtained using the reference radioligand [ 3 H]-citalopram, a well-characterized and highly selective serotonin reuptake inhibitor (83±22 fmol/mg protein). Specific binding sites of both [ 3 H]-DASB and [ 3 H]-citalopram were similarly and nonuniformly distributed throughout the rhesus central nervous system, in a pattern consistent with serotonin transporter localization reported for human brain. Regional serotonin transporter densities, estimated from optical densities of the autoradiographic images, were well correlated between the two radioligands. Finally, DASB and fluoxetine showed dose-dependent full inhibition of [ 3 H]-citalopram binding in a competition autoradiographic study, with K i values in close agreement with those obtained from rhesus brain homogenates. This side-by-side comparison of [ 3 H]-DASB and [ 3 H]-citalopram binding sites in rhesus tissue homogenates and in adjacent rhesus brain slices provides additional support for the use of [ 11 C]-DASB to assess the availability and distribution of serotonin transporters in nonhuman primates

  8. Dissecting the mechanisms of squirrel monkey (Saimiri boliviensis) social learning.

    Science.gov (United States)

    Hopper, Lm; Holmes, An; Williams, LE; Brosnan, Sf

    2013-01-01

    Although the social learning abilities of monkeys have been well documented, this research has only focused on a few species. Furthermore, of those that also incorporated dissections of social learning mechanisms, the majority studied either capuchins (Cebus apella) or marmosets (Callithrix jacchus). To gain a broader understanding of how monkeys gain new skills, we tested squirrel monkeys (Saimiri boliviensis) which have never been studied in tests of social learning mechanisms. To determine whether S. boliviensis can socially learn, we ran "open diffusion" tests with monkeys housed in two social groups (N = 23). Over the course of 10 20-min sessions, the monkeys in each group observed a trained group member retrieving a mealworm from a bidirectional task (the "Slide-box"). Two thirds (67%) of these monkeys both learned how to operate the Slide-box and they also moved the door significantly more times in the direction modeled by the trained demonstrator than the alternative direction. To tease apart the underlying social learning mechanisms we ran a series of three control conditions with 35 squirrel monkeys that had no previous experience with the Slide-box. The first replicated the experimental open diffusion sessions but without the inclusion of a trained model, the second was a no-information control with dyads of monkeys, and the third was a 'ghost' display shown to individual monkeys. The first two controls tested for the importance of social support (mere presence effect) and the ghost display showed the affordances of the task to the monkeys. The monkeys showed a certain level of success in the group control (54% of subjects solved the task on one or more occasions) and paired controls (28% were successful) but none were successful in the ghost control. We propose that the squirrel monkeys' learning, observed in the experimental open diffusion tests, can be best described by a combination of social learning mechanisms in concert; in this case, those

  9. Evaluation of {sup 18}F-BCPP-EF for mitochondrial complex 1 imaging in the brain of conscious monkeys using PET

    Energy Technology Data Exchange (ETDEWEB)

    Tsukada, Hideo; Ohba, Hiroyuki; Kanazawa, Masakatsu; Kakiuchi, Takeharu; Harada, Norihiro [Hamamatsu Photonics K.K., Central Research Laboratory, Hamamatsu, Shizuoka (Japan)

    2014-04-15

    We have reported on the development of a novel PET probe, {sup 18}F-2-tert-butyl-4-chloro-5-{6-[2-(2-fluoroethoxy)-ethoxy] -pyridin-3-ylmethoxy}-2H-pyridazin-3-one ({sup 18}F-BCPP-EF), for quantitative imaging of mitochondrial complex 1 (MC-1) activity in the brain of the living rat. For clinical application in humans, translational research in the monkey was conducted. PET measurements with {sup 18}F-BCPP-EF were performed in young and old monkeys (Macaca mulatta) in a conscious state with arterial blood sampling. The binding specificity of {sup 18}F-BCPP-EF was evaluated with rotenone, a specific MC-1 inhibitor, in young animals. The binding (total distribution volume, V{sub T}) of {sup 18}F-BCPP-EF was calculated using Logan graphical analysis, and one-tissue compartment model (1-TC) and two-tissue compartment model (2-TC) analyses using a metabolite-corrected plasma input function. F-BCPP-EF was rapidly taken up into the brain just after intravenous injection, peaked between 10 and 20 min after injection, and was then gradually eliminated. The 2-TC analysis provided a better fit than the 1-TC analysis, and the V{sub T} values from the 2-TC analysis correlated well with those from the Logan plot. With predosing with rotenone, {sup 18}F-BCPP-EF showed a higher uptake peak in the brain, followed by more rapid elimination thereafter than in the vehicle condition, resulting in significant reductions in 2-TC V{sub T} values in all regions. In old animals, the kinetics of {sup 18}F-BCPP-EF were slightly slower with lower peak levels than in young animals, resulting age-related reductions in {sup 18}F-BCPP-EF binding in all brain regions. The present study demonstrated that {sup 18}F-BCPP-EF may be a potential PET probe for quantitative imaging MC-1 activity in the living brain using PET. (orig.)

  10. IL-6 is Upregulated in Late-Stage Disease in Monkeys Experimentally Infected with Trypanosoma brucei rhodesiense

    Directory of Open Access Journals (Sweden)

    Dawn Nyawira Maranga

    2013-01-01

    Full Text Available The management of human African trypanosomiasis (HAT is constrained by lack of simple-to-use diagnostic, staging, and treatment tools. The search for novel biomarkers is, therefore, essential in the fight against HAT. The current study aimed at investigating the potential of IL-6 as an adjunct parameter for HAT stage determination in vervet monkey model. Four adult vervet monkeys (Chlorocebus aethiops were experimentally infected with Trypanosoma brucei rhodesiense and treated subcuratively at 28 days after infection (dpi to induce late stage disease. Three noninfected monkeys formed the control group. Cerebrospinal fluid (CSF and blood samples were obtained at weekly intervals and assessed for various biological parameters. A typical HAT-like infection was observed. The late stage was characterized by significant (P<0.05 elevation of CSF IL-6, white blood cell count, and total protein starting 35 dpi with peak levels of these parameters coinciding with relapse parasitaemia. Brain immunohistochemical staining revealed an increase in brain glial fibrillary acidic protein expression indicative of reactive astrogliosis in infected animals which were euthanized in late-stage disease. The elevation of IL-6 in CSF which accompanied other HAT biomarkers indicates onset of parasite neuroinvasion and show potential for use as an adjunct late-stage disease biomarker in the Rhodesian sleeping sickness.

  11. Working and waiting for better rewards: self-control in two monkey species (Cebus apella and Macaca mulatta).

    Science.gov (United States)

    Evans, Theodore A; Perdue, Bonnie M; Parrish, Audrey E; Beran, Michael J

    2014-03-01

    Self-control is typically defined as choosing a greater, delayed reward over a lesser, more immediate reward. However, in nature, there are other costs besides delay associated with obtaining the greatest outcome including increased effort, potential punishment, and low probability of reward. Effort is an interesting case because it sometimes impairs self-control, by acting as an additional cost, and at other times facilitates self-control, by distracting one from impulsive options. Additionally, different species may perform differently in effortful self-control tasks, based on their natural ecology. To gain insight into these aspects of self-control behavior, we examined capuchin monkeys' and rhesus monkeys' self-control in separate working and waiting choice tasks. We hypothesized that capuchins would show greater self-control in the working task, given their naturally higher activity level, whereas rhesus would perform similarly in both tasks. Rhesus performed as predicted, whereas contrary to our hypothesis, capuchins exhibited lesser performance in the working task. Nonetheless, these results may still stem from inherent species differences interacting with details of the methodology. Capuchins, being highly energetic and social monkeys, may have divided their energy and attention between the working task and other elements of the test environment such as visible group mates or manipulanda. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Predicting human chronically paralyzed muscle force: a comparison of three mathematical models.

    Science.gov (United States)

    Frey Law, Laura A; Shields, Richard K

    2006-03-01

    Chronic spinal cord injury (SCI) induces detrimental musculoskeletal adaptations that adversely affect health status, ranging from muscle paralysis and skin ulcerations to osteoporosis. SCI rehabilitative efforts may increasingly focus on preserving the integrity of paralyzed extremities to maximize health quality using electrical stimulation for isometric training and/or functional activities. Subject-specific mathematical muscle models could prove valuable for predicting the forces necessary to achieve therapeutic loading conditions in individuals with paralyzed limbs. Although numerous muscle models are available, three modeling approaches were chosen that can accommodate a variety of stimulation input patterns. To our knowledge, no direct comparisons between models using paralyzed muscle have been reported. The three models include 1) a simple second-order linear model with three parameters and 2) two six-parameter nonlinear models (a second-order nonlinear model and a Hill-derived nonlinear model). Soleus muscle forces from four individuals with complete, chronic SCI were used to optimize each model's parameters (using an increasing and decreasing frequency ramp) and to assess the models' predictive accuracies for constant and variable (doublet) stimulation trains at 5, 10, and 20 Hz in each individual. Despite the large differences in modeling approaches, the mean predicted force errors differed only moderately (8-15% error; P=0.0042), suggesting physiological force can be adequately represented by multiple mathematical constructs. The two nonlinear models predicted specific force characteristics better than the linear model in nearly all stimulation conditions, with minimal differences between the two nonlinear models. Either nonlinear mathematical model can provide reasonable force estimates; individual application needs may dictate the preferred modeling strategy.

  13. Metabolite analysis of [11C]Ro15-4513 in mice, rats, monkeys and humans

    International Nuclear Information System (INIS)

    Kida, T.; Noguchi, J.; Zhang, M.-R.; Suhara, T.; Suzuki, K.

    2003-01-01

    We performed in vitro and in vivo assays of the metabolism of [ 11 C]Ro15-4513 over time in the plasma of mice, rats, monkeys and humans, using a radio-HPLC equipped with a sensitive positron detector, in order to compare the metabolic rates of the radiopharmaceutical agent among the different animal species and to establish a highly sensitive analytical method for the radiotracer agent. We also examined the metabolism of [ 11 C]Ro15-4513 in the brain tissue of mice and rats. The analytical method used in this study permitted detection of even extremely low levels of radioactivity (approximately 5,000 dpm). In vitro experiments revealed that [ 11 C]Ro15-4513 in the blood was metabolized to hydrolysate [ 11 C]A. The species were classified in descending order of the metabolic rate of the radiotracer in vitro as follows; mice, rats, and monkeys/humans. In the in vitro experiment, the percentage of the unchanged drug in the plasma at 60 minutes postdose was 9% in mice, 70% in rats, 97% in monkeys, and 98% in humans. In vivo metabolite analysis in the blood showed the presence of two radioactive metabolites, consisting of one hydrolysate [ 11 C]A and another unidentified substance. The species were classified in descending order of the metabolic rate of the radiotracer in vivo as follows; mice, rats/humans, and monkeys. The percentage of the unchanged drug in the plasma was 6% in mice, 21% in rats, 26% in humans, and 40% in monkeys. Furthermore, the in vitro and in vivo experiments conducted to analyze the metabolism of [ 11 C]Ro15-4513 in the brain tissue of mice and rats revealed that the radiotracer was metabolized to some extent in the brain tissue of these animals. In the in vivo experiment, the percentage of the unchanged drug at 60 min postdose was 86% in the brain tissue of mice and 88% in the brain tissue of rats, while in the in vitro experiment, the corresponding percentage was 93% in mice, and 91% in rats

  14. Brain Computer Interfaces, a Review

    Directory of Open Access Journals (Sweden)

    Luis Fernando Nicolas-Alonso

    2012-01-01

    Full Text Available A brain-computer interface (BCI is a hardware and software communications system that permits cerebral activity alone to control computers or external devices. The immediate goal of BCI research is to provide communications capabilities to severely disabled people who are totally paralyzed or ‘locked in’ by neurological neuromuscular disorders, such as amyotrophic lateral sclerosis, brain stem stroke, or spinal cord injury. Here, we review the state-of-the-art of BCIs, looking at the different steps that form a standard BCI: signal acquisition, preprocessing or signal enhancement, feature extraction, classification and the control interface. We discuss their advantages, drawbacks, and latest advances, and we survey the numerous technologies reported in the scientific literature to design each step of a BCI. First, the review examines the neuroimaging modalities used in the signal acquisition step, each of which monitors a different functional brain activity such as electrical, magnetic or metabolic activity. Second, the review discusses different electrophysiological control signals that determine user intentions, which can be detected in brain activity. Third, the review includes some techniques used in the signal enhancement step to deal with the artifacts in the control signals and improve the performance. Fourth, the review studies some mathematic algorithms used in the feature extraction and classification steps which translate the information in the control signals into commands that operate a computer or other device. Finally, the review provides an overview of various BCI applications that control a range of devices.

  15. Brain Computer Interfaces, a Review

    Science.gov (United States)

    Nicolas-Alonso, Luis Fernando; Gomez-Gil, Jaime

    2012-01-01

    A brain-computer interface (BCI) is a hardware and software communications system that permits cerebral activity alone to control computers or external devices. The immediate goal of BCI research is to provide communications capabilities to severely disabled people who are totally paralyzed or ‘locked in’ by neurological neuromuscular disorders, such as amyotrophic lateral sclerosis, brain stem stroke, or spinal cord injury. Here, we review the state-of-the-art of BCIs, looking at the different steps that form a standard BCI: signal acquisition, preprocessing or signal enhancement, feature extraction, classification and the control interface. We discuss their advantages, drawbacks, and latest advances, and we survey the numerous technologies reported in the scientific literature to design each step of a BCI. First, the review examines the neuroimaging modalities used in the signal acquisition step, each of which monitors a different functional brain activity such as electrical, magnetic or metabolic activity. Second, the review discusses different electrophysiological control signals that determine user intentions, which can be detected in brain activity. Third, the review includes some techniques used in the signal enhancement step to deal with the artifacts in the control signals and improve the performance. Fourth, the review studies some mathematic algorithms used in the feature extraction and classification steps which translate the information in the control signals into commands that operate a computer or other device. Finally, the review provides an overview of various BCI applications that control a range of devices. PMID:22438708

  16. Change in brain activity through virtual reality-based brain-machine communication in a chronic tetraplegic subject with muscular dystrophy.

    Science.gov (United States)

    Hashimoto, Yasunari; Ushiba, Junichi; Kimura, Akio; Liu, Meigen; Tomita, Yutaka

    2010-09-16

    For severely paralyzed people, a brain-computer interface (BCI) provides a way of re-establishing communication. Although subjects with muscular dystrophy (MD) appear to be potential BCI users, the actual long-term effects of BCI use on brain activities in MD subjects have yet to be clarified. To investigate these effects, we followed BCI use by a chronic tetraplegic subject with MD over 5 months. The topographic changes in an electroencephalogram (EEG) after long-term use of the virtual reality (VR)-based BCI were also assessed. Our originally developed BCI system was used to classify an EEG recorded over the sensorimotor cortex in real time and estimate the user's motor intention (MI) in 3 different limb movements: feet, left hand, and right hand. An avatar in the internet-based VR was controlled in accordance with the results of the EEG classification by the BCI. The subject was trained to control his avatar via the BCI by strolling in the VR for 1 hour a day and then continued the same training twice a month at his home. After the training, the error rate of the EEG classification decreased from 40% to 28%. The subject successfully walked around in the VR using only his MI and chatted with other users through a voice-chat function embedded in the internet-based VR. With this improvement in BCI control, event-related desynchronization (ERD) following MI was significantly enhanced (p < 0.01) for feet MI (from -29% to -55%), left-hand MI (from -23% to -42%), and right-hand MI (from -22% to -51%). These results show that our subject with severe MD was able to learn to control his EEG signal and communicate with other users through use of VR navigation and suggest that an internet-based VR has the potential to provide paralyzed people with the opportunity for easy communication.

  17. Change in brain activity through virtual reality-based brain-machine communication in a chronic tetraplegic subject with muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Liu Meigen

    2010-09-01

    Full Text Available Abstract Background For severely paralyzed people, a brain-computer interface (BCI provides a way of re-establishing communication. Although subjects with muscular dystrophy (MD appear to be potential BCI users, the actual long-term effects of BCI use on brain activities in MD subjects have yet to be clarified. To investigate these effects, we followed BCI use by a chronic tetraplegic subject with MD over 5 months. The topographic changes in an electroencephalogram (EEG after long-term use of the virtual reality (VR-based BCI were also assessed. Our originally developed BCI system was used to classify an EEG recorded over the sensorimotor cortex in real time and estimate the user's motor intention (MI in 3 different limb movements: feet, left hand, and right hand. An avatar in the internet-based VR was controlled in accordance with the results of the EEG classification by the BCI. The subject was trained to control his avatar via the BCI by strolling in the VR for 1 hour a day and then continued the same training twice a month at his home. Results After the training, the error rate of the EEG classification decreased from 40% to 28%. The subject successfully walked around in the VR using only his MI and chatted with other users through a voice-chat function embedded in the internet-based VR. With this improvement in BCI control, event-related desynchronization (ERD following MI was significantly enhanced (p Conclusions These results show that our subject with severe MD was able to learn to control his EEG signal and communicate with other users through use of VR navigation and suggest that an internet-based VR has the potential to provide paralyzed people with the opportunity for easy communication.

  18. Evaluation of σ-1 receptor radioligand 18F-FTC-146 in rats and squirrel monkeys using PET

    DEFF Research Database (Denmark)

    James, Michelle L; Shen, Bin; Nielsen, Carsten Haagen

    2014-01-01

    . Pretreatment with known S1R compounds, haloperidol, or BD1047, before radioligand administration, significantly attenuated (18)F-FTC-146 accumulation in all rat brain regions by approximately 85% (P ...-FTC-146 was observed in rat plasma. Preliminary monkey PET/MRI studies demonstrated specific accumulation of (18)F-FTC-146 in the brain (mainly in cortical structures, cerebellum, and vermis) that could be attenuated by pretreatment with haloperidol. HPLC of monkey plasma suggested radioligand metabolism...

  19. In vivo tomographic study of cerebral blood perfusion with SPECT in hemiparkinsonian monkeys

    International Nuclear Information System (INIS)

    Chen Shengdi; Xu Delong

    1994-01-01

    The authors present data on the utility of functional brain imaging with 99m Tc-ECD and SPECT in the study of MPTP induced hemiparkinsonism in monkeys. Injection of MPTP into the right common carotid artery of 10 rhesus monkeys produced hemiparkinsonism in the contralateral limbs which responded to antiparkinsonian medication. The unilateral neurotoxicity of the MPTP treated side was confirmed biochemically by marked reduction of DA contents in the nigrostriatum and histologically by selective neuronal loss in the substantia nigra. These monkeys with hemiparkinsonism were studied with SPECT using 99m Tc-ECD as perfusion marker. The results of brain scanning showed that the cerebral blood perfusion of MPTP treated side was significantly depleted 20∼90 days after MPTP intoxication, and returned to normal 8 months after perfusion. The experiment indicates that abnormal cerebral blood perfusion is involved in the course of parkinsonian pathophysiology

  20. Cognitive performance of juvenile monkeys after chronic fluoxetine treatment.

    Science.gov (United States)

    Golub, Mari S; Hackett, Edward P; Hogrefe, Casey E; Leranth, Csaba; Elsworth, John D; Roth, Robert H

    2017-08-01

    Potential long term effects on brain development are a concern when drugs are used to treat depression and anxiety in childhood. In this study, male juvenile rhesus monkeys (three-four years of age) were dosed with fluoxetine or vehicle (N=16/group) for two years. Histomorphometric examination of cortical dendritic spines conducted after euthanasia at one year postdosing (N=8/group) suggested a trend toward greater dendritic spine synapse density in prefrontal cortex of the fluoxetine-treated monkeys. During dosing, subjects were trained for automated cognitive testing, and evaluated with a test of sustained attention. After dosing was discontinued, sustained attention, recognition memory and cognitive flexibility were evaluated. Sustained attention was affected by fluoxetine, both during and after dosing, as indexed by omission errors. Response accuracy was not affected by fluoxetine in post-dosing recognition memory and cognitive flexibility tests, but formerly fluoxetine-treated monkeys compared to vehicle controls had more missed trial initiations and choices during testing. Drug treatment also interacted with genetic and environmental variables: MAOA genotype (high- and low transcription rate polymorphisms) and testing location (upper or lower tier of cages). Altered development of top-down cortical regulation of effortful attention may be relevant to this pattern of cognitive test performance after juvenile fluoxetine treatment. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Spontaneous Metacognition in Rhesus Monkeys.

    Science.gov (United States)

    Rosati, Alexandra G; Santos, Laurie R

    2016-09-01

    Metacognition is the ability to think about thinking. Although monitoring and controlling one's knowledge is a key feature of human cognition, its evolutionary origins are debated. In the current study, we examined whether rhesus monkeys (Macaca mulatta; N = 120) could make metacognitive inferences in a one-shot decision. Each monkey experienced one of four conditions, observing a human appearing to hide a food reward in an apparatus consisting of either one or two tubes. The monkeys tended to search the correct location when they observed this baiting event, but engaged in information seeking-by peering into a center location where they could check both potential hiding spots-if their view had been occluded and information seeking was possible. The monkeys only occasionally approached the center when information seeking was not possible. These results show that monkeys spontaneously use information about their own knowledge states to solve naturalistic foraging problems, and thus provide the first evidence that nonhumans exhibit information-seeking responses in situations with which they have no prior experience. © The Author(s) 2016.

  2. New {alpha}{sub 1}-adrenoceptor antagonists derived from the antipsychotic sertindole - carbon-11 labelling and pet examination of brain uptake in the cynomolgus monkey

    Energy Technology Data Exchange (ETDEWEB)

    Balle, Thomas E-mail: tb@dfuni.dk; Halldin, Christer; Andersen, Linus; Hjorth Alifrangis, Lene; Badolo, Lassina; Gjervig Jensen, Klaus; Chou, Y.-W.; Andersen, Kim; Perregaard, Jens; Farde, Lars

    2004-04-01

    Central {alpha}{sub 1}-adrenergic receptors are potential targets for recently developed antipsychotic drugs. Two new 11C labeled potent and selective {alpha}{sub 1}-adrenoceptor antagonists, 1- [2- [4-[1-(4-fluorophenyl)-5-(2-[{sup 11}C]methyl-tetrazol-5-yl)-1H-indol-3-yl]-1- pipridinyl]ethyl]-imidazolidin-2-one ([{sup 11}C]2) and 1- [2- [4-[1-(4-fluorophenyl)-5-(1-[{sup 11}C]methyl-(1,2,3-triazol-4-yl) -1H-indol-3-yl]- 1-piperidinyl]ethyl]-imidazolidin-2-one ([{sup 11}C]3) were prepared and evaluated for imaging of central {alpha}{sub 1}-adrenergic receptors in the cynomolgus monkey brain. For both compounds, the total brain radioactivity was only about 0.6% of the radioactivity injected i.v. There was no evident binding in regions known to contain {alpha}{sub 1}-adrenoceptors. This observation suggests that the affinity of the radioligands in primates in vivo is not sufficient to provide a signal for specific binding that can be differentiated from the background. In addition, active efflux by P-glycoprotein may be responsible for the low total brain-uptake of the two radioligands. Both compounds showed a highly polarised and verapamile sensitive transport across monolayers of Caco-2 cells. The total brain-uptake of [{sup 3}H]2 was 6 times higher in mdr1a(-/-) knock-out mice lacking the gene encoding P-glycoprotein compared to wild type mice. Pretreatment of one monkey with Cyclosporin A (15 mg/kg) resulted in 40% higher brain uptake for [{sup 11}C]3 when compared with baseline. These observations support the view that efflux by P-glycoprotein can be of quantitative importance for the total brain-uptake of some PET radioligands.

  3. Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress

    Science.gov (United States)

    Gould, Elizabeth; Tanapat, Patima; McEwen, Bruce S.; Flügge, Gabriele; Fuchs, Eberhard

    1998-01-01

    Although granule cells continue to be added to the dentate gyrus of adult rats and tree shrews, this phenomenon has not been demonstrated in the dentate gyrus of adult primates. To determine whether neurons are produced in the dentate gyrus of adult primates, adult marmoset monkeys (Callithrix jacchus) were injected with BrdU and perfused 2 hr or 3 weeks later. BrdU is a thymidine analog that is incorporated into proliferating cells during S phase. A substantial number of cells in the dentate gyrus of adult monkeys incorporated BrdU and ≈80% of these cells had morphological characteristics of granule neurons and expressed a neuronal marker by the 3-week time point. Previous studies suggest that the proliferation of granule cell precursors in the adult dentate gyrus can be inhibited by stress in rats and tree shrews. To test whether an aversive experience has a similar effect on cell proliferation in the primate brain, adult marmoset monkeys were exposed to a resident-intruder model of stress. After 1 hr in this condition, the intruder monkeys were injected with BrdU and perfused 2 hr later. The number of proliferating cells in the dentate gyrus of the intruder monkeys was compared with that of unstressed control monkeys. We found that a single exposure to this stressful experience resulted in a significant reduction in the number of these proliferating cells. Our results suggest that neurons are produced in the dentate gyrus of adult monkeys and that the rate of precursor cell proliferation can be affected by a stressful experience. PMID:9501234

  4. Cup tool use by squirrel monkeys.

    Science.gov (United States)

    Buckmaster, Christine L; Hyde, Shellie A; Parker, Karen J; Lyons, David M

    2015-12-01

    Captive-born male and female squirrel monkeys spontaneously 'invented' a cup tool use technique to Contain (i.e., hold and control) food they reduced into fragments for consumption and to Contain water collected from a valve to drink. Food cup use was observed more frequently than water cup use. Observations indicate that 68% (n = 39/57) of monkeys in this population used a cup (a plastic slip cap) to Contain food, and a subset of these monkeys, 10% (n = 4/39), also used a cup to Contain water. Cup use was optional and did not replace, but supplemented, the hand/arm-to-mouth eating and direct valve drinking exhibited by all members of the population. Strategies monkeys used to bring food and cups together for food processing activity at preferred upper-level perching areas, in the arboreal-like environment in which they lived, provides evidence that monkeys may plan food processing activity with the cups. Specifically, prior to cup use monkeys obtained a cup first before food, or obtained food and a cup from the floor simultaneously, before transporting both items to upper-level perching areas. After food processing activity with cups monkeys rarely dropped the cups and more often placed the cups onto perching. Monkeys subsequently returned to use cups that they previously placed on perching after food processing activity. The latter behavior is consistent with the possibility that monkeys may keep cups at preferred perching sites for future food processing activity and merits experimental investigation. Reports of spontaneous tool use by squirrel monkeys are rare and this is the first report of population-level tool use. These findings offer insights into the cognitive abilities of squirrel monkeys and provide a new context for behavior studies with this genus and for comparative studies with other primates. © 2015 Wiley Periodicals, Inc.

  5. Neurokinin-3 Receptor Binding in Guinea Pig, Monkey, and Human Brain: In Vitro and in Vivo Imaging Using the Novel Radioligand, [18F]Lu AF10628.

    Science.gov (United States)

    Varnäs, Katarina; Finnema, Sjoerd J; Stepanov, Vladimir; Takano, Akihiro; Tóth, Miklós; Svedberg, Marie; Møller Nielsen, Søren; Khanzhin, Nikolay A; Juhl, Karsten; Bang-Andersen, Benny; Halldin, Christer; Farde, Lars

    2016-08-01

    Previous autoradiography studies have suggested a marked interspecies variation in the neuroanatomical localization and expression levels of the neurokinin 3 receptor, with high density in the brain of rat, gerbil, and guinea pig, but at the time offered no conclusive evidence for its presence in the human brain. Hitherto available radioligands have displayed low affinity for the human neurokinin 3 receptor relative to the rodent homologue and may thus not be optimal for cross-species analyses of the expression of this protein. A novel neurokinin 3 receptor radioligand, [(18)F]Lu AF10628 ((S)-N-(cyclobutyl(3-fluorophenyl)methyl)-8-fluoro-2-((3-[(18)F]-fluoropropyl)amino)-3-methyl-1-oxo-1,2-dihydroisoquinoline-4-carboxamide), was synthesized and used for autoradiography studies in cryosections from guinea pig, monkey, and human brain as well as for positron emission tomography studies in guinea pig and monkey. The results confirmed previous observations of interspecies variation in the neurokinin 3 receptor brain localization with more extensive distribution in guinea pig than in primate brain. In the human brain, specific binding to the neurokinin 3 receptor was highest in the amygdala and in the hypothalamus and very low in other regions examined. Positron emission tomography imaging showed a pattern consistent with that observed using autoradiography. The radioactivity was, however, found to accumulate in skull bone, which limits the use of this radioligand for in vivo quantification of neurokinin 3 receptor binding. Species differences in the brain distribution of neurokinin 3 receptors should be considered when using animal models for predicting human neurokinin 3 receptor pharmacology. For positron emission tomography imaging of brain neurokinin 3 receptors, additional work is required to develop a radioligand with more favorable in vivo properties. © The Author 2016. Published by Oxford University Press on behalf of CINP.

  6. The serotonin transporter in rhesus monkey brain: comparison of DASB and citalopram binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Zeng Zhizhen [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States)]. E-mail: zhizhen_zeng@merck.com; Chen, T.-B. [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States); Miller, Patricia J. [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States); Dean, Dennis [Labeled Compound Synthesis Group, Drug Metabolism, Merck Research Laboratories, Rahway, NJ 07065-0900 (United States); Tang, Y.S. [Labeled Compound Synthesis Group, Drug Metabolism, Merck Research Laboratories, Rahway, NJ 07065-0900 (United States); Sur, Cyrille [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States); Williams, David L. [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States)

    2006-05-15

    We have characterized the interaction of the serotonin transporter ligand [{sup 3}H]-N,N-dimethyl-2-(2-amino-4-cyanophenylthio)-benzylamine (DASB) with rhesus monkey brain in vitro using tissue homogenate binding and autoradiographic mapping. [{sup 3}H]-DASB, a tritiated version of the widely used [{sup 11}C] positron emission tomography tracer, was found to selectively bind to a single population of sites with high affinity (K {sub d}=0.20{+-}0.04 nM). The serotonin transporter density (B {sub max}) obtained for rhesus frontal cortex was found to be 66{+-}8 fmol/mg protein using [{sup 3}H]-DASB, similar to the B {sub max} value obtained using the reference radioligand [{sup 3}H]-citalopram, a well-characterized and highly selective serotonin reuptake inhibitor (83{+-}22 fmol/mg protein). Specific binding sites of both [{sup 3}H]-DASB and [{sup 3}H]-citalopram were similarly and nonuniformly distributed throughout the rhesus central nervous system, in a pattern consistent with serotonin transporter localization reported for human brain. Regional serotonin transporter densities, estimated from optical densities of the autoradiographic images, were well correlated between the two radioligands. Finally, DASB and fluoxetine showed dose-dependent full inhibition of [{sup 3}H]-citalopram binding in a competition autoradiographic study, with K {sub i} values in close agreement with those obtained from rhesus brain homogenates. This side-by-side comparison of [{sup 3}H]-DASB and [{sup 3}H]-citalopram binding sites in rhesus tissue homogenates and in adjacent rhesus brain slices provides additional support for the use of [{sup 11}C]-DASB to assess the availability and distribution of serotonin transporters in nonhuman primates.

  7. Establishment of a rhesus monkey model of chronic temporal lobe epilepsy using repetitive unilateral intra-amygdala kainic acid injections.

    Science.gov (United States)

    Chi, Yajie; Wu, Bolin; Guan, Jianwei; Xiao, Kuntai; Lu, Ziming; Li, Xiao; Xu, Yuting; Xue, Shan; Xu, Qiang; Rao, Junhua; Guo, Yanwu

    2017-09-01

    Temporal lobe epilepsy (TLE) is a common type of acquired epilepsy refractory to medical treatment. As such, establishing animal models of this disease is critical to developing new and effective treatment modalities. Because of their small head size, rodents are not suitable for comprehensive electroencephalography (EEG) evaluation via scalp or subdural electrodes. Therefore, a larger primate model that closely recapitulates signs of TLE is needed; here we describe a rhesus monkey model resembling chronic TLE. Eight monkeys were divided into two groups: kainic acid (KA) group (n=6) and saline control group (n=2). Intra-amygdala KA injections were performed biweekly via an Ommaya device until obvious epileptiform discharges were recorded. Video-EEG recording was conducted intermittently throughout the experiment using both scalp and subdural electrodes. Brains were then analyzed for Nissl and glial fibrillary acid protein (GFAP) immunostaining. After 2-4 injections of KA (approximately 1.2-2.4mg, 0.12-0.24mg/kg), interictal epileptiform discharges (IEDs) were recorded in all KA-treated animals. Spontaneous recurrent seizures (SRSs) accompanied by symptoms mimicking temporal lobe absence (undetectable without EEG recording), but few mild motor signs, were recorded in 66.7% (four of six) KA-treated animals. Both IEDs and seizures indicated a primary epileptic zone in the right temporal region and contralateral discharges were later detected. Segmental pyramidal cell loss and gliosis were detected in the brain of a KA-treated monkey. Through a modified protocol of unilateral repetitive intra-amygdala KA injections, a rhesus monkey model with similar behavioral and brain electrical features as TLE was developed. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Mathematical models of human paralyzed muscle after long-term training

    OpenAIRE

    Frey Law, L.A.; Shields, R.K.

    2007-01-01

    Spinal cord injury (SCI) results in major musculoskeletal adaptations, including muscle atrophy, faster contractile properties, increased fatigability, and bone loss. The use of functional electrical stimulation (FES) provides a method to prevent paralyzed muscle adaptations in order to sustain force-generating capacity. Mathematical muscle models may be able to predict optimal activation strategies during FES, however muscle properties further adapt with long-term training. The purpose of th...

  9. Insulin/IGF signaling-related gene expression in the brain of a sporadic Alzheimer's disease monkey model induced by intracerebroventricular injection of streptozotocin.

    Science.gov (United States)

    Lee, Youngjeon; Kim, Young-Hyun; Park, Sang-Je; Huh, Jae-Won; Kim, Sang-Hyun; Kim, Sun-Uk; Kim, Ji-Su; Jeong, Kang-Jin; Lee, Kyoung-Min; Hong, Yonggeun; Lee, Sang-Rae; Chang, Kyu-Tae

    2014-01-01

    We reported previously that the intracerebroventricular streptozotocin (icv-STZ)-treated cynomolgus monkey showed regionally specific glucose hypometabolism in FDG-PET imaging, similar to that observed in the early stages of sporadic Alzheimer's disease (sAD). However, further pathological analyses of this model at the molecular level are needed to validate it as a feasible model for sAD. Two cynomolgus monkeys were injected with 2 mg/kg STZ into the cerebellomedullary cistern at day 1, 7 and 14. Two control monkeys were given normal saline. At 5 months after injection, the expression levels of genes encoding 9 upstream molecules in insulin/insulin-like growth factor (IGF) signaling and markers for 4 cell-type populations in the frontal cortex, hippocampus, posterior cingulate, precuneus, and occipital cortex of control and icv-STZ treated cynomolgus monkeys were examined. Real-time quantitative PCR analyses demonstrated that the overall mRNA expression of insulin/IGF signaling-related genes was mainly impaired in the anterior part of the cerebrum, frontal cortex, and hippocampus, similar to the early stage of sAD. The changes were accompanied by the loss of oligodendrocytes and neurons. The posterior part of the cerebrum did not show degenerative alterations. The present study provides important fundamental information on the icv-STZ monkey model for sAD. These results may help guide future studies using this model for the investigation of pathological mechanisms and the development of drugs for sAD.

  10. [11C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain

    International Nuclear Information System (INIS)

    Halldin, Christer; Erixon-Lindroth, Nina; Pauli, Stefan; Chou, Yuan-Hwa; Okubo, Yoshiro; Karlsson, Per; Lundkvist, Camilla; Olsson, Hans; Farde, Lars; Guilloteau, Denis; Emond, Patrick

    2003-01-01

    The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [ 11 C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/μmol). [ 11 C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55-65 min after injection. Displacement and pretreatment measurements using unlabelled β-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [ 11 C]PE2I binds selectively to DAT. In a preliminary study in one human subject the radioactivity ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8, respectively, at peak equilibrium, which appeared at 40-50 min and 20 min, respectively, after injection. The fraction of the total radioactivity in monkey and human plasma representing unchanged [ 11 C]PE2I was 15-20% at 40 min after injection. The present characterisation of binding in monkey and man suggests that [ 11 C]PE2I is a suitable PET radioligand for quantitative regional examination of DAT in man. (orig.)

  11. Brain machine interfaces combining microelectrode arrays with nanostructured optical biochemical sensors

    Science.gov (United States)

    Hajj-Hassan, Mohamad; Gonzalez, Timothy; Ghafer-Zadeh, Ebrahim; Chodavarapu, Vamsy; Musallam, Sam; Andrews, Mark

    2009-02-01

    Neural microelectrodes are an important component of neural prosthetic systems which assist paralyzed patients by allowing them to operate computers or robots using their neural activity. These microelectrodes are also used in clinical settings to localize the locus of seizure initiation in epilepsy or to stimulate sub-cortical structures in patients with Parkinson's disease. In neural prosthetic systems, implanted microelectrodes record the electrical potential generated by specific thoughts and relay the signals to algorithms trained to interpret these thoughts. In this paper, we describe novel elongated multi-site neural electrodes that can record electrical signals and specific neural biomarkers and that can reach depths greater than 8mm in the sulcus of non-human primates (monkeys). We hypothesize that additional signals recorded by the multimodal probes will increase the information yield when compared to standard probes that record just electropotentials. We describe integration of optical biochemical sensors with neural microelectrodes. The sensors are made using sol-gel derived xerogel thin films that encapsulate specific biomarker responsive luminophores in their nanostructured pores. The desired neural biomarkers are O2, pH, K+, and Na+ ions. As a prototype, we demonstrate direct-write patterning to create oxygen-responsive xerogel waveguide structures on the neural microelectrodes. The recording of neural biomarkers along with electrical activity could help the development of intelligent and more userfriendly neural prosthesis/brain machine interfaces as well as aid in providing answers to complex brain diseases and disorders.

  12. Reinnervation of Paralyzed Muscle by Nerve-Muscle-Endplate Band Grafting

    Science.gov (United States)

    2015-10-01

    Antoniadis G, Braun V, Rath SA, Richter HP. Evaluation of iatrogenic lesions in 722 surgically treated cases of peripheral nerve trauma. J Neurosurg...achieved by end-to-end approximation: review of 2,181 nerve lesions . Microsurgery. 1993;14(4):244- 246. 18 25. McAllister RM, Gilbert SE, Calder JS...innervation through irreparable damage to its nerve . DNI has been used for selective reinnervation of paralyzed laryngeal and facial muscles [15,16] as well

  13. Physiology and physiopathology of central type Benzodiazepine receptors: Study in the monkey and in human brain using positron emission tomography

    International Nuclear Information System (INIS)

    Hantraye, P.

    1987-01-01

    A new non-invasive technique that allows to study in a living subject central type benzodiazepine receptors is developed. A combined approach is applied using a specific positron-emitting radiotracer for the in vivo labelling of the receptors and positron emission tomography allowing, by external detection, a quantitative determination of tissue radioactivity. The radioligand used for the in vivo labelling of benzodiazepine receptors is the antagonist RO 15-1788 labelled with carbon 11. The various stages of the study are described: in vivo characterization in the monkey of central type benzodiazepine receptors; characterization of central type benzodiazepine receptors in human brain using selective molecules for the BZ1 benzodiazepine subclass; demonstration of the heterogeneity of central type benzodiazepine receptors in the brain; study of pathological alteration of benzodiazepine receptors in experimental epilepsy [fr

  14. Contributions of Lateral and Orbital Frontal Regions to Abstract Rule Acquisition and Reversal in Monkeys

    Science.gov (United States)

    La Camera, Giancarlo; Bouret, Sebastien; Richmond, Barry J.

    2018-01-01

    The ability to learn and follow abstract rules relies on intact prefrontal regions including the lateral prefrontal cortex (LPFC) and the orbitofrontal cortex (OFC). Here, we investigate the specific roles of these brain regions in learning rules that depend critically on the formation of abstract concepts as opposed to simpler input-output associations. To this aim, we tested monkeys with bilateral removals of either LPFC or OFC on a rapidly learned task requiring the formation of the abstract concept of same vs. different. While monkeys with OFC removals were significantly slower than controls at both acquiring and reversing the concept-based rule, monkeys with LPFC removals were not impaired in acquiring the task, but were significantly slower at rule reversal. Neither group was impaired in the acquisition or reversal of a delayed visual cue-outcome association task without a concept-based rule. These results suggest that OFC is essential for the implementation of a concept-based rule, whereas LPFC seems essential for its modification once established. PMID:29615854

  15. Positron emission tomography (PET) study of the alterations in brain pharmacokinetics of methamphetamine in methamphetamine sensitized animals

    International Nuclear Information System (INIS)

    Nakamura, Hitoshi

    2001-01-01

    I investigated the differences in brain pharmacokinetics of [ 11 C]methamphetamine ([ 11 C]MAP) in normal and MAP sensitized animals using positron emission tomography (PET). [ 11 C]MAP was synthesized by an automated on-line [ 11 C]methylation system. I newly produced MAP sensitized dog and monkey by repeated MAP treatment. The maximal level of accumulation of [ 11 C]MAP in the sensitized dog brain was 1.4 times higher than that in the control. This result suggests the changes in the pharmacokinetic profile of MAP in the brain affect the development or expression of MAP-induced behavioral sensitization. However, the overaccumulation of [ 11 C]MAP in the sensitized monkey brain was not observed due to the influence of anesthesia. (author)

  16. Positron emission tomography (PET) study of the alterations in brain pharmacokinetics of methamphetamine in methamphetamine sensitized animals

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Hitoshi [Tohoku Univ., Sendai (Japan). Hospital

    2001-08-01

    I investigated the differences in brain pharmacokinetics of [{sup 11}C]methamphetamine ([{sup 11}C]MAP) in normal and MAP sensitized animals using positron emission tomography (PET). [{sup 11}C]MAP was synthesized by an automated on-line [{sup 11}C]methylation system. I newly produced MAP sensitized dog and monkey by repeated MAP treatment. The maximal level of accumulation of [{sup 11}C]MAP in the sensitized dog brain was 1.4 times higher than that in the control. This result suggests the changes in the pharmacokinetic profile of MAP in the brain affect the development or expression of MAP-induced behavioral sensitization. However, the overaccumulation of [{sup 11}C]MAP in the sensitized monkey brain was not observed due to the influence of anesthesia. (author)

  17. [{sup 11}C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain

    Energy Technology Data Exchange (ETDEWEB)

    Halldin, Christer; Erixon-Lindroth, Nina; Pauli, Stefan; Chou, Yuan-Hwa; Okubo, Yoshiro; Karlsson, Per; Lundkvist, Camilla; Olsson, Hans; Farde, Lars [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, 17176, Stockholm (Sweden); Guilloteau, Denis; Emond, Patrick [INSERM U316 Universite Francois Rabelais, Tours (France)

    2003-09-01

    The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2E-enyl)-2{beta}-carbomethoxy-3{beta}-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [{sup 11}C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/{mu}mol). [{sup 11}C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55-65 min after injection. Displacement and pretreatment measurements using unlabelled {beta}-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [{sup 11}C]PE2I binds selectively to DAT. In a preliminary study in one human subject the radioactivity ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8, respectively, at peak equilibrium, which appeared at 40-50 min and 20 min, respectively, after injection. The fraction of the total radioactivity in monkey and human plasma representing unchanged [{sup 11}C]PE2I was 15-20% at 40 min after injection. The present characterisation of binding in monkey and man suggests that [{sup 11}C]PE2I is a suitable PET radioligand for quantitative regional examination of DAT in man. (orig.)

  18. Predicting human chronically paralyzed muscle force: a comparison of three mathematical models

    OpenAIRE

    Frey Law, Laura A.; Shields, Richard K.

    2005-01-01

    Chronic spinal cord injury (SCI) induces detrimental musculoskeletal adaptations that adversely affect health status, ranging from muscle paralysis and skin ulcerations to osteoporosis. SCI rehabilitative efforts may increasingly focus on preserving the integrity of paralyzed extremities to maximize health quality using electrical stimulation for isometric training and/or functional activities. Subject-specific mathematical muscle models could prove valuable for predicting the forces necessar...

  19. The effect of N-acetylated DL-penicillamin and DL-homocysteine thiolactone on the mercury distribution in adult rats, rat foetuses and macaca monkeys after exposure to methyl mercuric chloride

    International Nuclear Information System (INIS)

    Aaseth, J.; Wannag, A.; Norseth, T.; Institute of Occupational Health, Oslo, Norway)

    1976-01-01

    The distribution and excretion of mercury was studied in pregnant rats, given a single intravenous dose of 2 μmol/kg of CH 3 203 HgCl on the 13th day of pregnancy. Oral treatment for one week with N-acetyl-DL-penicillamine (4 mmol/kg per day) increased the mercury excretion in faces (from 45 to 120 nmol) and urine (from 9 to 160 nmol). Such treatment mobilized mercury from all the organs tested and the foetal and maternal brain levels of mercury were decreased to 1/5 and 1/3 of the controls, respectively. A four-day period of treatment with N-acetyl-DL-penicillamine started three days after the injection of methyl mercury reduced the foetal and maternal brain levels to 1/2 and 2/3 of the controls, respectively. The rapid removal of metal deposits following treatment with N-acetyl-DL-penicillamine is attributed to a free penetration of the complexing thiol into the tissue cells in question. No signs of toxicity were detected in monkeys given an effective daily dose of the agent (4 mmol/kg) for 6 days. In contrast N-acetyl-DL-homocysteine thiolactone was found to be toxic in the monkeys. In addition, the latter agent was ineffective in increasing the mercury elimination from the brains of monkeys, rats and rat foetuses. (author)

  20. From assistance towards restoration with epidural brain-computer interfacing.

    Science.gov (United States)

    Gharabaghi, Alireza; Naros, Georgios; Walter, Armin; Grimm, Florian; Schuermeyer, Marc; Roth, Alexander; Bogdan, Martin; Rosenstiel, Wolfgang; Birbaumer, Niels

    2014-01-01

    Today's implanted brain-computer interfaces make direct contact with the brain or even penetrate the tissue, bearing additional risks with regard to safety and stability. What is more, these approaches aim to control prosthetic devices as assistive tools and do not yet strive to become rehabilitative tools for restoring lost motor function. We introduced a less invasive, implantable interface by applying epidural electrocorticography in a chronic stroke survivor with a persistent motor deficit. He was trained to modulate his natural motor-related oscillatory brain activity by receiving online feedback. Epidural recordings of field potentials in the beta-frequency band projecting onto the anatomical hand knob proved most successful in discriminating between the attempt to move the paralyzed hand and to rest. These spectral features allowed for fast and reliable control of the feedback device in an online closed-loop paradigm. Only seven training sessions were required to significantly improve maximum wrist extension. For patients suffering from severe motor deficits, epidural implants may decode and train the brain activity generated during attempts to move with high spatial resolution, thus facilitating specific and high-intensity practice even in the absence of motor control. This would thus transform them from pure assistive devices to restorative tools in the context of reinforcement learning and neurorehabilitation.

  1. Remote and chronic access to the third cerebral ventricle of the unrestrained prepubertal rhesus monkey.

    Science.gov (United States)

    Gay, V L; Mikuma, N; Plant, T M

    1993-03-01

    One channel of a commercially available standard-size three-channel fluid swivel was modified to permit continuous access to the brain of unrestrained prepubertal rhesus monkeys via a continuous length of small-bore Teflon tube originating from a swivel device on top of the animal's cage and terminating in the third cerebral ventricle. This system was employed to achieve continuous access to the third cerebroventricle in four monkeys for periods of up to 12 mo. The value of the system for studies of the neurochemical control of hypothalamic-releasing factor secretion was established by monitoring adenohypophysial responses to neurotransmitter receptor agonists infused into the third ventricle. Specifically, repetitive infusions of morphine (30 micrograms/infusion) elicited a robust train of prolactin discharges, and third ventricular administration of N-methyl-DL-aspartic acid (NMA; 20 micrograms) resulted in striking discharges of LH.

  2. Nuclear weapon testing and the monkey business

    International Nuclear Information System (INIS)

    Murthy, M.S.S.

    1978-01-01

    Reasons for India's total ban on the export of rhesus monkeys to U.S. have been explained. The major reason is that some of the animals were used in nuclear weapon related radiation experiments. This was a clear violation of a stricture in the agreement about supply of monkeys. The stricture prohibited the use of animals for research concerning military operations, including nuclear weapon testing. It is pleaded that a strict enforcement of strictures rather than a total ban on the export of monkeys would be better in the interest of advancement of knowledge in human medicine and disease control. (M.G.B.)

  3. Deep brain stimulation of the bilateral nucleus accumbens in normal rhesus monkey.

    Science.gov (United States)

    Li, Nan; Gao, Li; Wang, Xue-lian; Chen, Lei; Fang, Wei; Ge, Shun-nan; Gao, Guo-dong

    2013-01-09

    The nucleus accumbens (NAc) has been considered as a novel target of deep brain stimulation (DBS) for intractable psychiatric disorders. Quite a few questions exist about this new treatment, and might be explored in nonhuman primate models. There are several reports on DBS of brain nucleus other than NAc in nonhuman primates. Therefore, we stereotactically implanted the electrodes into bilateral NAc under the guidance of MRI using a clinical Leksell stereotactic system in normal rhesus monkeys. NAc could be recognized as the area of continuity between the caudate nucleus and putamen in the coronal sections, which is beneath the internal capsule, and the gray matter nucleus between the ventromedial prefrontal cortex and anterior commissure in axial sections, which is medial to the putamen. NAc is mainly at a point 2.0-3.0 mm inferior, 3.0-4.0 mm anterior, and 4.5-5.5 mm lateral to the anterior commissure. The electrodes were implanted accurately and connected to an implantable pulse generator subcutaneously. After recovery from surgery, stimulation with a variety of parameters was trialed, and continuous stimulation at 90 μs, 3.5 V, 160, or 60 Hz was administered individually for 7 days. The behaviors and spontaneous locomotor activity of the animals did not change significantly during stimulation. This is the first report on DBS of NAc in nonhuman primates to the best of our knowledge. Bilateral electrical stimulation of NAc is a safe treatment. This model could be helpful in further studies on the clinical use of NAc stimulation for psychiatric disorders and for a better understanding of the functions of this nucleus.

  4. Functional restoration of the paralyzed diaphragm in high cervical quadriplegia via phrenic nerve neurotization utilizing the functional spinal accessory nerve.

    Science.gov (United States)

    Yang, Ming-liang; Li, Jian-jun; Zhang, Shao-cheng; Du, Liang-jie; Gao, Feng; Li, Jun; Wang, Yu-ming; Gong, Hui-ming; Cheng, Liang

    2011-08-01

    The authors report a case of functional improvement of the paralyzed diaphragm in high cervical quadriplegia via phrenic nerve neurotization using a functional spinal accessory nerve. Complete spinal cord injury at the C-2 level was diagnosed in a 44-year-old man. Left diaphragm activity was decreased, and the right diaphragm was completely paralyzed. When the level of metabolism or activity (for example, fever, sitting, or speech) slightly increased, dyspnea occurred. The patient underwent neurotization of the right phrenic nerve with the trapezius branch of the right spinal accessory nerve at 11 months postinjury. Four weeks after surgery, training of the synchronous activities of the trapezius muscle and inspiration was conducted. Six months after surgery, motion was observed in the previously paralyzed right diaphragm. The lung function evaluation indicated improvements in vital capacity and tidal volume. This patient was able to sit in a wheelchair and conduct outdoor activities without assisted ventilation 12 months after surgery.

  5. Increased blood pressure can reduce fatigue of thenar muscles paralyzed after spinal cord injury

    NARCIS (Netherlands)

    Butler, JE; Ribot-Ciscar, E; Zijdewind, Inge; Thomas, CK

    The aim of this study was to evaluate whether increases in blood pressure, and presumably muscle perfusion pressure, improve the endurance of thenar muscles paralyzed chronically by cervical spinal cord injury (SCI). Resting mean arterial pressure (MAP) was low in all eight subjects (64 +/- 2 mmHg).

  6. The effect of angiotensin receptor neprilysin inhibitor, sacubitril/valsartan, on central nervous system amyloid-β concentrations and clearance in the cynomolgus monkey

    International Nuclear Information System (INIS)

    Schoenfeld, Heidi A.; West, Tim; Verghese, Philip B.; Holubasch, Mary; Shenoy, Neeta; Kagan, David; Buono, Chiara; Zhou, Wei; DeCristofaro, Marc; Douville, Julie; Goodrich, Geoffrey G.; Mansfield, Keith; Saravanan, Chandra; Cumin, Frederic; Webb, Randy L.; Bateman, Randall J.

    2017-01-01

    Sacubitril/valsartan (LCZ696) is the first angiotensin receptor neprilysin inhibitor approved to reduce cardiovascular mortality and hospitalization in patients with heart failure with reduced ejection fraction. As neprilysin (NEP) is one of several enzymes known to degrade amyloid-β (Aβ), there is a theoretical risk of Aβ accumulation following long-term NEP inhibition. The primary objective of this study was to evaluate the potential effects of sacubitril/valsartan on central nervous system clearance of Aβ isoforms in cynomolgus monkeys using the sensitive Stable Isotope Labeling Kinetics (SILK™)-Aβ methodology. The in vitro selectivity of valsartan, sacubitril, and its active metabolite sacubitrilat was established; sacubitrilat did not inhibit other human Aβ-degrading metalloproteases. In a 2-week study, sacubitril/valsartan (50 mg/kg/day) or vehicle was orally administered to female cynomolgus monkeys in conjunction with SILK™-Aβ. Despite low cerebrospinal fluid (CSF) and brain penetration, CSF exposure to sacubitril was sufficient to inhibit NEP and resulted in an increase in the elimination half-life of Aβ1-42 (65.3%; p = 0.026), Aβ1-40 (35.2%; p = 0.04) and Aβtotal (29.8%; p = 0.04) acutely; this returned to normal as expected with repeated dosing for 15 days. CSF concentrations of newly generated Aβ (AUC (0–24 h) ) indicated elevations in the more aggregable form Aβ1-42 on day 1 (20.4%; p = 0.039) and day 15 (34.7%; p = 0.0003) and in shorter forms Aβ1-40 (23.4%; p = 0.009), Aβ1-38 (64.1%; p = 0.0001) and Aβtotal (50.45%; p = 0.00002) on day 15. However, there were no elevations in any Aβ isoforms in the brains of these monkeys on day 16. In a second study cynomolgus monkeys were administered sacubitril/valsartan (300 mg/kg) or vehicle control for 39 weeks; no microscopic brain changes or Aβ deposition, as assessed by immunohistochemical staining, were present. Further clinical studies are planned to address the relevance of these

  7. The effect of angiotensin receptor neprilysin inhibitor, sacubitril/valsartan, on central nervous system amyloid-β concentrations and clearance in the cynomolgus monkey

    Energy Technology Data Exchange (ETDEWEB)

    Schoenfeld, Heidi A., E-mail: heidi.schoenfeld@novartis.com [Novartis Institutes for BioMedical Research, East Hanover, NJ (United States); West, Tim; Verghese, Philip B.; Holubasch, Mary [C2N Diagnostics, St. Louis, MO (United States); Shenoy, Neeta; Kagan, David; Buono, Chiara [Novartis Institutes for BioMedical Research, Cambridge, MA (United States); Zhou, Wei; DeCristofaro, Marc [Novartis Institutes for BioMedical Research, East Hanover, NJ (United States); Douville, Julie [Charles River Laboratories ULC, Montreal, Quebec (Canada); Goodrich, Geoffrey G. [Charles River Laboratories, Inc., Reno, NV (United States); Mansfield, Keith; Saravanan, Chandra [Novartis Institutes for BioMedical Research, Cambridge, MA (United States); Cumin, Frederic [Novartis Institutes for BioMedical Research, Basel (Switzerland); Webb, Randy L. [Novartis Pharmaceuticals Corporation, East Hanover, NJ (United States); Bateman, Randall J. [Department of Neurology, Washington University School of Medicine, St. Louis, MO (United States)

    2017-05-15

    Sacubitril/valsartan (LCZ696) is the first angiotensin receptor neprilysin inhibitor approved to reduce cardiovascular mortality and hospitalization in patients with heart failure with reduced ejection fraction. As neprilysin (NEP) is one of several enzymes known to degrade amyloid-β (Aβ), there is a theoretical risk of Aβ accumulation following long-term NEP inhibition. The primary objective of this study was to evaluate the potential effects of sacubitril/valsartan on central nervous system clearance of Aβ isoforms in cynomolgus monkeys using the sensitive Stable Isotope Labeling Kinetics (SILK™)-Aβ methodology. The in vitro selectivity of valsartan, sacubitril, and its active metabolite sacubitrilat was established; sacubitrilat did not inhibit other human Aβ-degrading metalloproteases. In a 2-week study, sacubitril/valsartan (50 mg/kg/day) or vehicle was orally administered to female cynomolgus monkeys in conjunction with SILK™-Aβ. Despite low cerebrospinal fluid (CSF) and brain penetration, CSF exposure to sacubitril was sufficient to inhibit NEP and resulted in an increase in the elimination half-life of Aβ1-42 (65.3%; p = 0.026), Aβ1-40 (35.2%; p = 0.04) and Aβtotal (29.8%; p = 0.04) acutely; this returned to normal as expected with repeated dosing for 15 days. CSF concentrations of newly generated Aβ (AUC{sub (0–24} {sub h)}) indicated elevations in the more aggregable form Aβ1-42 on day 1 (20.4%; p = 0.039) and day 15 (34.7%; p = 0.0003) and in shorter forms Aβ1-40 (23.4%; p = 0.009), Aβ1-38 (64.1%; p = 0.0001) and Aβtotal (50.45%; p = 0.00002) on day 15. However, there were no elevations in any Aβ isoforms in the brains of these monkeys on day 16. In a second study cynomolgus monkeys were administered sacubitril/valsartan (300 mg/kg) or vehicle control for 39 weeks; no microscopic brain changes or Aβ deposition, as assessed by immunohistochemical staining, were present. Further clinical studies are planned to address the relevance

  8. Early changes of cortical blood flow, brain temperature and electrical activity after whole-body irradiation of the monkey (Macaca fascicularis) (dose range: 3-20 Gy)

    International Nuclear Information System (INIS)

    Court, L.; Gourmelon, P.; Mestries, J.C.

    1987-02-01

    A polyparametric investigation was carried out on 31 monkeys chronically wearing bioinstrumentation allowing to get and process simultaneously local brain blood flow, cerebral temperature, and energies in various frequency bands of the brain electrical activity. This method, which supplied data during several consecutive days, made it possible to study both the biological rhythms at the level of the various parameters, and their fast variations. The effects of whole-body gamma or neutron-gamma irradiation were studied in the 3-20 Gy dose range. Immediate changes after exposure demonstrated different radiosensitivities at the level of the rhythms of the various parameters, and/or their recovery, as well as dose-effect relationships [fr

  9. Comparative plasma lipidome between human and cynomolgus monkey: are plasma polar lipids good biomarkers for diabetic monkeys?

    Directory of Open Access Journals (Sweden)

    Guanghou Shui

    Full Text Available BACKGROUND: Non-human primates (NHP are now being considered as models for investigating human metabolic diseases including diabetes. Analyses of cholesterol and triglycerides in plasma derived from NHPs can easily be achieved using methods employed in humans. Information pertaining to other lipid species in monkey plasma, however, is lacking and requires comprehensive experimental analysis. METHODOLOGIES/PRINCIPAL FINDINGS: We examined the plasma lipidome from 16 cynomolgus monkey, Macaca fascicularis, using liquid chromatography coupled with mass spectrometry (LC/MS. We established novel analytical approaches, which are based on a simple gradient elution, to quantify polar lipids in plasma including (i glycerophospholipids (phosphatidylcholine, PC; phosphatidylethanolamine, PE; phosphatidylinositol, PI; phosphatidylglycerol, PG; phosphatidylserine, PS; phosphatidic acid, PA; (ii sphingolipids (sphingomyelin, SM; ceramide, Cer; Glucocyl-ceramide, GluCer; ganglioside mannoside 3, GM3. Lipidomic analysis had revealed that the plasma of human and cynomolgus monkey were of similar compositions, with PC, SM, PE, LPC and PI constituting the major polar lipid species present. Human plasma contained significantly higher levels of plasmalogen PE species (p<0.005 and plasmalogen PC species (p<0.0005, while cynomolgus monkey had higher levels of polyunsaturated fatty acyls (PUFA in PC, PE, PS and PI. Notably, cynomolgus monkey had significantly lower levels of glycosphingolipids, including GluCer (p<0.0005 and GM(3 (p<0.0005, but higher level of Cer (p<0.0005 in plasma than human. We next investigated the biochemical alterations in blood lipids of 8 naturally occurring diabetic cynomolgus monkeys when compared with 8 healthy controls. CONCLUSIONS: For the first time, we demonstrated that the plasma of human and cynomolgus monkey were of similar compositions, but contained different mol distribution of individual molecular species. Diabetic monkeys

  10. Two forms of acid alpha-D-mannosidase in monkey brain: evidence for the co-existence of high mannose and complex oligosaccharides in one form.

    Science.gov (United States)

    Mathur, R; Alvares, K; Balasubramanian, A S

    1984-09-28

    Lysosomal alpha-D-mannosidase of monkey brain existed in two forms. One form of mannosidase was bound to the Ricinus communis agglutinin120 (RCA1)-Sepharose and could be specifically eluted with lactose. The other form did not bind to the RCA1-Sepharose. Both forms of mannosidase could bind to a similar extent to the immobilized brain lysosomal receptor protein. Both the forms were purified to apparent homogeneity. Neutral sugar analysis by GLC showed the presence of glucose, mannose and galactose in the RCA1-Sepharose bindable mannosidase and glucose and mannose in the non-bindable mannosidase. Several other brain lysosomal hydrolases did not bind to the RCA1-Sepharose. The results suggested the existence of only high mannose oligosaccharides in the RCA1 non-bindable mannosidase and both high mannose and complex oligosaccharides in the bindable mannosidase.

  11. Fluoxetine Administration in Juvenile Monkeys: Implications for Pharmacotherapy in Children

    Directory of Open Access Journals (Sweden)

    Mari S. Golub

    2018-02-01

    Full Text Available Fluoxetine therapy has been approved for children with major depressive disorder and obsessive compulsive disorder for over 14 years and has expanded to other childhood behavior disorders. As use increases, more detail on fluoxetine effects during juvenile brain development can help maintain safe and effective use of this therapy. Here, a narrative review is provided of previously published findings from a large nonhuman primate project. Fluoxetine was administered to juvenile male rhesus monkeys for an extended period (2 years prior to puberty. Compared to controls, treated monkeys showed sleep disruption, facilitated social interaction, greater impulsivity, and impaired sustained attention during treatment. No effects on growth were seen. Metabolomics assays characterized a distinctive response to fluoxetine and demonstrated individual differences that were related to the impulsivity measure. Fluoxetine interactions with monoamine oxidase A polymorphisms that influenced behavior and metabolomics markers were an important, previously unrecognized finding of our studies. After treatment was discontinued, some behavioral effects persisted, but short-term memory and cognitive flexibility testing did not show drug effects. This detailed experimental work can contribute to clinical research and continued safe and effective fluoxetine pharmacotherapy in children.

  12. Cortico-cortical connections of areas 44 and 45B in the macaque monkey.

    Science.gov (United States)

    Frey, Stephen; Mackey, Scott; Petrides, Michael

    2014-04-01

    In the human brain, areas 44 and 45 constitute Broca's region, the ventrolateral frontal region critical for language production. The homologues of these areas in the macaque monkey brain have been established by direct cytoarchitectonic comparison with the human brain. The cortical areas that project monosynaptically to areas 44 and 45B in the macaque monkey brain require clarification. Fluorescent retrograde tracers were placed in cytoarchitectonic areas 44 and 45B of the macaque monkey, as well as in the anterior part of the inferior parietal lobule and the superior temporal gyrus. The results demonstrate that ipsilateral afferent connections of area 44 arise from local frontal areas, including rostral premotor cortical area 6, from secondary somatosensory cortex, the caudal insula, and the cingulate motor region. Area 44 is strongly linked with the anterior inferior parietal lobule (particularly area PFG and the adjacent anterior intraparietal sulcus). Input from the temporal lobe is limited to the fundus of the superior temporal sulcus extending caudal to the central sulcus. There is also input from the sulcal part of area Tpt in the upper bank of the superior temporal sulcus. Area 45B shares some of the connections of area 44, but can be distinguished from area 44 by input from the caudal inferior parietal lobule (area PG) and significant input from the part of the superior temporal sulcus that extends anterior to the central sulcus. Area 45B also receives input from visual association cortex that is not observed in area 44. The results have provided a clarification of the relative connections of areas 44 and 45B of the ventrolateral frontal region which, in the human brain, subserves certain aspects of language processing. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Striatal dopamine D2/3 receptor regulation by stress inoculation in squirrel monkeys

    Directory of Open Access Journals (Sweden)

    Alex G. Lee

    2016-06-01

    Full Text Available Intermittent mildly stressful situations provide opportunities to learn, practice, and improve coping in a process called stress inoculation. Stress inoculation also enhances cognitive control and response inhibition of impulsive motivated behavior. Cognitive control and motivation have been linked to striatal dopamine D2 and/or D3 receptors (DRD2/3 in rodents, monkeys, and humans. Here, we study squirrel monkeys randomized early in life to stress inoculation with or without maternal companionship and a no-stress control treatment condition. Striatal DRD2/3 availability in adulthood was measured in vivo by [11C]raclopride binding using positron emission tomography (PET. DRD2/3 availability was greater in caudate and putamen compared to ventral striatum as reported in PET studies of humans and other non-human primates. DRD2/3 availability in ventral striatum was also consistently greater in stress inoculated squirrel monkeys compared to no-stress controls. Squirrel monkeys exposed to stress inoculation in the presence of their mother did not differ from squirrel monkeys exposed to stress inoculation without maternal companionship. Similar effects in different social contexts extend the generality of our findings and together suggest that stress inoculation increases striatal DRD2/3 availability as a correlate of cognitive control in squirrel monkeys.

  14. Dynamic ensemble coding of saccades in the monkey superior colliculus.

    NARCIS (Netherlands)

    Goossens, H.H.L.M.; Opstal, A.J. van

    2006-01-01

    The deeper layers of the midbrain superior colliculus (SC) contain a topographic motor map in which a localized population of cells is recruited for each saccade, but how the brain stem decodes the dynamic SC output is unclear. Here we analyze saccade-related responses in the monkey SC to test a new

  15. Central projections of intrinsically photosensitive retinal ganglion cells in the macaque monkey

    DEFF Research Database (Denmark)

    Hannibal, J; Kankipati, L; Strang, C E

    2014-01-01

    ). The ipRGCs regulate other nonimage-forming visual functions such as the pupillary light reflex, masking behavior, and light-induced melatonin suppression. To evaluate whether PACAP-immunoreactive retinal projections are useful as a marker for central projection of ipRGCs in the monkey brain, we......, supporting previous retrograde tracer studies demonstrating that melanopsin-containing retinal projections reach areas in the primate brain involved in both image- and nonimage-forming visual processing....

  16. Plasma disappearance, urine excretion, and tissue distribution of ribavirin in rats and rhesus monkeys

    International Nuclear Information System (INIS)

    Ferrara, E.A.; Oishi, J.S.; Wannemacher, R.W. Jr.; Stephen, E.L.

    1981-01-01

    Ribavirin has been shown to have broad-spectrum antiviral. To study its tissue distribution and disappearance rate, a single dose of 10 mg/kg which contained 10 microCi of [14C]ribavirin was injected intravenously into rhesus monkeys and intramuscularly into monkeys and rats. Except for peak plasma concentrations and the initial phases of the plasma disappearance and urine excretion curves, no significant difference was observed between plasma, tissue, or urine values for intramuscularly or intravenously injected monkeys. Plasma disappearance curves were triphasic; plasma concentrations of ribavirin were similar for both monkeys and rats. Rats excreted ribavirin in the urine more rapidly and to a greater extent (82% excreted in 24 h) than did monkeys (60% excreted in 72 h). In the rat, only 3% of the injected [14C]ribavirin was detected in expired CO2. Therefore, for both species, urine was the major route for the elimination of labeled ribavirin and its metabolites from the body. In monkeys, the amount of parent drug in blood cells increased through 48 h and remained stable for 72 h, whereas in rats, ribavirin decreased at a rate similar to the plasma disappearance curve. Concentrations of ribavirin at 8 h were consistently higher in monkeys than in rats for all tissues except the brain. Thus, these differences in blood cellular components and organ content and in urine excretion suggested that there was greater tissue retention of ribavirin in monkeys than in rats

  17. Attitudes of children and adolescents toward persons who are deaf, blind, paralyzed or intellectually disabled

    NARCIS (Netherlands)

    Laat, S. de; Freriksen, E.; Vervloed, M.P.J.

    2013-01-01

    This study aimed to explore Dutch students’ attitudes toward deaf, blind, paralyzed or intellectually disabled persons and to determine whether age, self-esteem, gender, religion and familiarity with a disabled person have a significant effect on these attitudes. The attitudes of 200 high school and

  18. The Development of the Basal Ganglia in Capuchin Monkeys (Cebus apella)

    Science.gov (United States)

    Phillips, Kimberley A.; Sobieski, Courtney A.; Gilbert, Valerie R.; Chiappini-Williamson, Christine; Sherwood, Chet C.; Strick, Peter L.

    2010-01-01

    The basal ganglia are subcortical structures involved in the planning, initiation and regulation of movement as well as a variety of non-motor, cognitive and affective functions. Capuchin monkeys share several important characteristics of development with humans, including a prolonged infancy and juvenile period, a long lifespan, and complex manipulative abilities. This makes capuchins important comparative models for understanding age-related neuroanatomical changes in these structures. Here we report developmental volumetric data on the three subdivisions of the basal ganglia, the caudate, putamen and globus pallidus in brown capuchin monkeys (Cebus apella). Based on a cross-sectional sample, we describe brain development in 28 brown capuchin monkeys (male n = 17, female n = 11; age range = 2 months – 20 years) using high-resolution structural MRI. We found that the raw volumes of the putamen and caudate varied significantly with age, decreasing in volume from birth through early adulthood. Notably, developmental changes did not differ between sexes. Because these observed developmental patterns are similar to humans, our results suggest that capuchin monkeys may be useful animal models for investigating neurodevelopmental disorders of the basal ganglia. PMID:20227397

  19. Operant conditioning of neural activity in freely behaving monkeys with intracranial reinforcement.

    Science.gov (United States)

    Eaton, Ryan W; Libey, Tyler; Fetz, Eberhard E

    2017-03-01

    Operant conditioning of neural activity has typically been performed under controlled behavioral conditions using food reinforcement. This has limited the duration and behavioral context for neural conditioning. To reward cell activity in unconstrained primates, we sought sites in nucleus accumbens (NAc) whose stimulation reinforced operant responding. In three monkeys, NAc stimulation sustained performance of a manual target-tracking task, with response rates that increased monotonically with increasing NAc stimulation. We recorded activity of single motor cortex neurons and documented their modulation with wrist force. We conditioned increased firing rates with the monkey seated in the training booth and during free behavior in the cage using an autonomous head-fixed recording and stimulating system. Spikes occurring above baseline rates triggered single or multiple electrical pulses to the reinforcement site. Such rate-contingent, unit-triggered stimulation was made available for periods of 1-3 min separated by 3-10 min time-out periods. Feedback was presented as event-triggered clicks both in-cage and in-booth, and visual cues were provided in many in-booth sessions. In-booth conditioning produced increases in single neuron firing probability with intracranial reinforcement in 48 of 58 cells. Reinforced cell activity could rise more than five times that of non-reinforced activity. In-cage conditioning produced significant increases in 21 of 33 sessions. In-cage rate changes peaked later and lasted longer than in-booth changes, but were often comparatively smaller, between 13 and 18% above non-reinforced activity. Thus intracranial stimulation reinforced volitional increases in cortical firing rates during both free behavior and a controlled environment, although changes in the latter were more robust. NEW & NOTEWORTHY Closed-loop brain-computer interfaces (BCI) were used to operantly condition increases in muscle and neural activity in monkeys by delivering

  20. Alterations in energy metabolism, neuroprotection and visual signal transduction in the retina of Parkinsonian, MPTP-treated monkeys.

    Directory of Open Access Journals (Sweden)

    Laura Campello

    Full Text Available Parkinson disease is mainly characterized by the degeneration of dopaminergic neurons in the central nervous system, including the retina. Different interrelated molecular mechanisms underlying Parkinson disease-associated neuronal death have been put forward in the brain, including oxidative stress and mitochondrial dysfunction. Systemic injection of the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP to monkeys elicits the appearance of a parkinsonian syndrome, including morphological and functional impairments in the retina. However, the intracellular events leading to derangement of dopaminergic and other retinal neurons in MPTP-treated animal models have not been so far investigated. Here we have used a comparative proteomics approach to identify proteins differentially expressed in the retina of MPTP-treated monkeys. Proteins were solubilized from the neural retinas of control and MPTP-treated animals, labelled separately with two different cyanine fluorophores and run pairwise on 2D DIGE gels. Out of >700 protein spots resolved and quantified, 36 were found to exhibit statistically significant differences in their expression levels, of at least ± 1.4-fold, in the parkinsonian monkey retina compared with controls. Most of these spots were excised from preparative 2D gels, trypsinized and subjected to MALDI-TOF MS and LC-MS/MS analyses. Data obtained were used for protein sequence database interrogation, and 15 different proteins were successfully identified, of which 13 were underexpressed and 2 overexpressed. These proteins were involved in key cellular functional pathways such as glycolysis and mitochondrial electron transport, neuronal protection against stress and survival, and phototransduction processes. These functional categories underscore that alterations in energy metabolism, neuroprotective mechanisms and signal transduction are involved in MPTP-induced neuronal degeneration in the retina, in similarity to

  1. Functional MRI of the vocalization-processing network in the macaque brain

    Directory of Open Access Journals (Sweden)

    Michael eOrtiz-Rios

    2015-04-01

    Full Text Available Using functional magnetic resonance imaging in awake behaving monkeys we investigated how species-specific vocalizations are represented in auditory and auditory-related regions of the macaque brain. We found clusters of active voxels along the ascending auditory pathway that responded to various types of complex sounds: inferior colliculus (IC, medial geniculate nucleus (MGN, auditory core, belt, and parabelt cortex, and other parts of the superior temporal gyrus (STG and sulcus (STS. Regions sensitive to monkey calls were most prevalent in the anterior STG, but some clusters were also found in frontal and parietal cortex on the basis of comparisons between responses to calls and environmental sounds. Surprisingly, we found that spectrotemporal control sounds derived from the monkey calls (scrambled calls also activated the parietal and frontal regions. Taken together, our results demonstrate that species-specific vocalizations in rhesus monkeys activate preferentially the auditory ventral stream, and in particular areas of the antero-lateral belt and parabelt.

  2. Brain-state classification and a dual-state decoder dramatically improve the control of cursor movement through a brain-machine interface

    Science.gov (United States)

    Sachs, Nicholas A.; Ruiz-Torres, Ricardo; Perreault, Eric J.; Miller, Lee E.

    2016-02-01

    Objective. It is quite remarkable that brain machine interfaces (BMIs) can be used to control complex movements with fewer than 100 neurons. Success may be due in part to the limited range of dynamical conditions under which most BMIs are tested. Achieving high-quality control that spans these conditions with a single linear mapping will be more challenging. Even for simple reaching movements, existing BMIs must reduce the stochastic noise of neurons by averaging the control signals over time, instead of over the many neurons that normally control movement. This forces a compromise between a decoder with dynamics allowing rapid movement and one that allows postures to be maintained with little jitter. Our current work presents a method for addressing this compromise, which may also generalize to more highly varied dynamical situations, including movements with more greatly varying speed. Approach. We have developed a system that uses two independent Wiener filters as individual components in a single decoder, one optimized for movement, and the other for postural control. We computed an LDA classifier using the same neural inputs. The decoder combined the outputs of the two filters in proportion to the likelihood assigned by the classifier to each state. Main results. We have performed online experiments with two monkeys using this neural-classifier, dual-state decoder, comparing it to a standard, single-state decoder as well as to a dual-state decoder that switched states automatically based on the cursor’s proximity to a target. The performance of both monkeys using the classifier decoder was markedly better than that of the single-state decoder and comparable to the proximity decoder. Significance. We have demonstrated a novel strategy for dealing with the need to make rapid movements while also maintaining precise cursor control when approaching and stabilizing within targets. Further gains can undoubtedly be realized by optimizing the performance of the

  3. Uptake and metabolism of [3H]testosterone in the brain, pituitary gland and genital tract of the male cynomolgus monkey

    International Nuclear Information System (INIS)

    Bonsall, R.W.; Rees, H.D.; Micheal, R.P.

    1986-01-01

    To study the mechanism by which testosterone restores the sexual potency of castrated cynomolgus monkeys, two males (body weights 5.2 and 5.3 kg) were castrated and, 3 days later, injected with 3 mCi [ 3 H]testosterone ([ 3 H]T) as an intravenous bolus. After 30 min, males were killed and brains and samples of other tissues were rapidly removed and placed on ice. Samples were dissected from the right halves of the brain and homogenized. Purified cell nuclei were prepared and ether extracts were analyzed by reverse-phase HPCL. Generally, unchanged [ 3 H]T was the major form of radioactivity in brain and pituitary gland, but in cell nuclei from hypothalamus, preoptic area and amygdala, a large proportion (34 - 61%) was in the form of [ 3 H]estradiol ([ 4 H]E 2 ). Little or no [ 3 H]dihydrotestosterone ([ 3 H]DHT) was detected in cell nuclei from any brain region or from pituitary gland. However, [ 3 H]DHT was the major form (61 - 95%) of radioactivity in cell nuclei from glans penis, prostrate and seminal vesicles. In autoradiograms of the left halves of the same brains, the percentage of cells that accumulated radioactivity in their nuclei was high in specific regions of the hypothalamus, preoptic areas and amygdala. The authors conclude that the peripheral actions of T are mediated via DHT, but its central actions are dependent on unchanged T or on E 2 formed locally by aromatization

  4. Why Is That Dog Paralyzed? A Problem-Based Case & Laboratory Exercise about Neuromuscular Transmission

    Science.gov (United States)

    Milanick, Mark; Graham, Kerri; Wessel, Melissa

    2013-01-01

    Students are provided with a mystery concerning dogs that are paralyzed. This motivates a laboratory exercise to measure parameters from the dog's "blood" to determine whether the paralysis is due to pesticide poisoning or an autoimmune attack on nerve myelin. Most of the materials are available from the grocery store. The real-world nature of the…

  5. Changes in nonhuman primate brain function following chronic alcohol consumption in previously naïve animals.

    Science.gov (United States)

    Rowland, Jared A; Stapleton-Kotloski, Jennifer R; Alberto, Greg E; Davenport, April T; Kotloski, Robert J; Friedman, David P; Godwin, Dwayne W; Daunais, James B

    2017-08-01

    Chronic alcohol abuse is associated with neurophysiological changes in brain activity; however, these changes are not well localized in humans. Non-human primate models of alcohol abuse enable control over many potential confounding variables associated with human studies. The present study utilized high-resolution magnetoencephalography (MEG) to quantify the effects of chronic EtOH self-administration on resting state (RS) brain function in vervet monkeys. Adolescent male vervet monkeys were trained to self-administer ethanol (n=7) or an isocaloric malto-dextrin solution (n=3). Following training, animals received 12 months of free access to ethanol. Animals then underwent RS magnetoencephalography (MEG) and subsequent power spectral analysis of brain activity at 32 bilateral regions of interest associated with the chronic effects of alcohol use. demonstrate localized changes in brain activity in chronic heavy drinkers, including reduced power in the anterior cingulate cortex, hippocampus, and amygdala as well as increased power in the right medial orbital and parietal areas. The current study is the first demonstration of whole-head MEG acquisition in vervet monkeys. Changes in brain activity were consistent with human electroencephalographic studies; however, MEG was able to extend these findings by localizing the observed changes in power to specific brain regions. These regions are consistent with those previously found to exhibit volume loss following chronic heavy alcohol use. The ability to use MEG to evaluate changes in brain activity following chronic ethanol exposure provides a potentially powerful tool to better understand both the acute and chronic effects of alcohol on brain function. Published by Elsevier B.V.

  6. Evaluation of neonatal squirrel monkeys receiving tritiated water throughout gestation

    International Nuclear Information System (INIS)

    Jones, D.C.L.; Krebs, J.S.; Sasmore, D.P.; Mitoma, C.

    1980-01-01

    Pregnant squirrel monkeys received tritiated water (HTO) in the drinking water throughout gestation at levels ranging from 16 to 1000 times the permissible level for human consumption (0.003 μCi/ml), resulting in mean body water HTO levels ranging from 0.05 to 3.1 μCi/ml. There were no discernible effects of HTO administration on the newborn progeny in terms of body weight, body dimensions, selected organ weights (brain, heart, adrenal, kidney, liver, spleen), hematologic patterns, and histology of selected organs and tissues (adrenal, kidney, liver, lung, brain, pancreas, jejunum, pituitary, spleen, testes, thymus, skin) other than ovaries. The number of primary oocytes in female progeny decreased markedly with increasing levels of HTO in maternal drinking water. Quantitative analysis of neonate ovaries, testes, brain tissue, and retinal tissue is in progress. No effects of HTO administration on maternal body weight, gestation time, or maintenance of pregnancy to full term were observed. Body weights of HTO-treated inseminated females that did not deliver were less than control weights, but the lack of dose dependence implies that this effect may have been associated with a stimulus characteristic of the HTO administration rather than with irradiation

  7. Characterization of 4-[18F]-ADAM as an imaging agent for SERT in non-human primate brain using PET: a dynamic study

    International Nuclear Information System (INIS)

    Chen, Yu-An; Huang, Wen-Sheng; Lin, Yaoh-Shiang; Cheng, Cheng-Yi; Liu, Ren-Shyan; Wang, Shyh-Jen; Li, I-Hsun; Huang, San-Yuan; Shiue, Chyng-Yann; Chen, Cheng-Yu; Ma, Kuo-Hsing

    2012-01-01

    Introduction: Serotonin transporter (SERT) has been associated with many psychiatric diseases. This study investigated the biodistribution of a serotonin transporter imaging agent, N,N-dimethyl-2-(2-amino-4- 18 F-fluorophenylthio)benzylamine (4-[ 18 F]-ADAM), in nonhuman primate brain using positron emission tomography (PET). Methods: Six and four Macaca cyclopis monkeys were used to determine the transit time (i.e., time necessary to reach biodistribution equilibrium) and the reproducibility of 4-[ 18 F]-ADAM biodistribution in the brain, respectively. The sensitivity and specificity of 4-[ 18 F]-ADAM binding to SERT were evaluated in one monkey challenged with different doses of fluoxetine and one monkey treated with 3,4-methylendioxymethamphetamine (MDMA). Dynamic PET imaging was performed for 3 h after 4-[ 18 F]-ADAM intravenous bolus injection. The specific uptake ratios (SURs) in the midbrain (MB), thalamus (TH), striatum (ST) and frontal cortex (FC) were calculated. Results: The distribution of 4-[ 18 F]-ADAM reached equilibrium 120–150 min after injection. The mean SURs were 2.49±0.13 in MB, 1.59±0.17 in TH, 1.35±0.06 in ST and 0.34±0.03 in FC, and the minimum variability was shown 120–150 min after 4-[ 18 F]-ADAM injection. Using SURs and intraclass coefficient of correlation, the test/retest variability was under 8% and above 0.8, respectively, in SERT-rich areas. Challenge with fluoxetin (0.75–2 mg) dose-dependently inhibited the SURs in various brain regions. 4-[ 18 F]-ADAM binding was markedly reduced in the brain of an MDMA-treated monkey compared to that in brains of normal controls. Conclusion: 4-[ 18 F]-ADAM appears to be a highly selective radioligand for imaging SERT in monkey brain.

  8. Constancy and variability in cortical structure. A study on synapses and dendritic spines in hedgehog and monkey.

    Science.gov (United States)

    Schüz, A; Demianenko, G P

    1995-01-01

    Synapses and dendritic spines were investigated in the parietal cortex of the hedgehog (Erinaceus europaeus) and the monkey (Macaca mulatta). There was no significant difference in the density of synapses between the two species (14 synapses/100 microns2 in the hedgehog, 15/100 microns2 in the monkey), neither in the size of the synaptic junctions, in the proportion of Type I and Type II synapses (8-10% were of Type II in the hedgehog, 10-14% in the monkey) nor in the proportion of perforated synapses (8% in the hedgehog, 5% in the monkey). The only striking difference at the electron microscopic level concerned the frequency of synapses in which the postsynaptic profile was deeply indented into the presynaptic terminal. Such synapses were 10 times more frequent in the monkey. Dendritic spines were investigated in Golgi-preparations. The density of spines along dendrites was similar in both species. The results are discussed with regard to connectivity in the cortex of small and large brains.

  9. Real-Time Control of an Articulatory-Based Speech Synthesizer for Brain Computer Interfaces.

    Directory of Open Access Journals (Sweden)

    Florent Bocquelet

    2016-11-01

    Full Text Available Restoring natural speech in paralyzed and aphasic people could be achieved using a Brain-Computer Interface (BCI controlling a speech synthesizer in real-time. To reach this goal, a prerequisite is to develop a speech synthesizer producing intelligible speech in real-time with a reasonable number of control parameters. We present here an articulatory-based speech synthesizer that can be controlled in real-time for future BCI applications. This synthesizer converts movements of the main speech articulators (tongue, jaw, velum, and lips into intelligible speech. The articulatory-to-acoustic mapping is performed using a deep neural network (DNN trained on electromagnetic articulography (EMA data recorded on a reference speaker synchronously with the produced speech signal. This DNN is then used in both offline and online modes to map the position of sensors glued on different speech articulators into acoustic parameters that are further converted into an audio signal using a vocoder. In offline mode, highly intelligible speech could be obtained as assessed by perceptual evaluation performed by 12 listeners. Then, to anticipate future BCI applications, we further assessed the real-time control of the synthesizer by both the reference speaker and new speakers, in a closed-loop paradigm using EMA data recorded in real time. A short calibration period was used to compensate for differences in sensor positions and articulatory differences between new speakers and the reference speaker. We found that real-time synthesis of vowels and consonants was possible with good intelligibility. In conclusion, these results open to future speech BCI applications using such articulatory-based speech synthesizer.

  10. Attitudes of Children and Adolescents toward Persons Who Are Deaf, Blind, Paralyzed or Intellectually Disabled

    Science.gov (United States)

    de Laat, Stijn; Freriksen, Ellen; Vervloed, Mathijs P. J.

    2013-01-01

    This study aimed to explore Dutch students' attitudes toward deaf, blind, paralyzed or intellectually disabled persons and to determine whether age, self-esteem, gender, religion and familiarity with a disabled person have a significant effect on these attitudes. The attitudes of 200 high school and 144 university students were determined with two…

  11. Intrapericardial Denervation: Responses to Water Immersion in Rhesus Monkeys

    Science.gov (United States)

    McKeever, Kenneth H.; Keil, Lanny C.; Sandler, Harold

    1995-01-01

    Eleven anesthetized rhesus monkeys were used to study cardiovascular, renal, and endocrine alterations associated with 120 min of head-out water immersion. Five animals underwent complete intrapericardial denervation using the Randall technique, while the remaining six monkeys served as intact controls. Each animal was chronically instrumented with an electromagnetic flow probe on the ascending aorta, a strain gauge pressure transducer implanted in the apex of the left ventricle (LV), and electrocardiogram leads anchored to the chest wall and LV. During immersion, LV end-diastolic pressure, urine flow, glomerular filtration rate, sodium excretion, and circulating atrial natriuretic peptide (ANP) each increased (P less than 0.05) for intact and denervated monkeys. There were no alterations in free water clearance in either group during immersion, yet fractional excretion of free water increased (P less than 0.05) in the intact monkeys. Plasma renin activity (PRA) decreased (P less than 0.05) during immersion in intact monkeys but not the denervated animals. Plasma vasopressin (PVP) concentration decreased (P less than 0.05) during the first 30 min of immersion in both groups but was not distinguishable from control by 60 min of immersion in denervated monkeys. These data demonstrate that complete cardiac denervation does not block the rise in plasma ANP or prevent the natriuresis associated with head-out water immersion. The suppression of PVP during the first minutes of immersion after complete cardiac denervation suggests that extracardiac sensing mechanisms associated with the induced fluid shifts may be responsible for the findings.

  12. Induced Neurocysticercosis in Rhesus Monkeys (Macaca mulatta Produces Clinical Signs and Lesions Similar to Natural Disease in Man

    Directory of Open Access Journals (Sweden)

    N. Chowdhury

    2014-01-01

    Full Text Available Neurocysticercosis is a serious endemic zoonosis resulting in increased cases of seizure and epilepsy in humans. The genesis of clinical manifestations of the disease through experimental animal models is poorly exploited. The monkeys may prove useful for the purpose due to their behavior and cognitive responses mimicking man. In this study, neurocysticercosis was induced in two rhesus monkeys each with 12,000 and 6,000 eggs, whereas three monkeys were given placebo. The monkeys given higher dose developed hyperexcitability, epileptic seizures, muscular tremors, digital cramps at 10 DPI, and finally paralysis of limbs, followed by death on 67 DPI, whereas the monkeys given lower dose showed delayed and milder clinical signs. On necropsy, all the infected monkeys showed numerous cysticerci in the brain. Histopathologically, heavily infected monkeys revealed liquefactive necrosis and formation of irregular cystic cavities lined by atrophied parenchymal septa with remnants of neuropil of the cerebrum. In contrast, the monkeys infected with lower dose showed formation of typical foreign body granulomas characterized by central liquefaction surrounded by chronic inflammatory response. It was concluded that the inflammatory and immune response exerted by the host against cysticerci, in turn, led to histopathological lesions and the resultant clinical signs thereof.

  13. Easy rider: monkeys learn to drive a wheelchair to navigate through a complex maze.

    Science.gov (United States)

    Etienne, Stephanie; Guthrie, Martin; Goillandeau, Michel; Nguyen, Tho Hai; Orignac, Hugues; Gross, Christian; Boraud, Thomas

    2014-01-01

    The neurological bases of spatial navigation are mainly investigated in rodents and seldom in primates. The few studies led on spatial navigation in both human and non-human primates are performed in virtual, not in real environments. This is mostly because of methodological difficulties inherent in conducting research on freely-moving monkeys in real world environments. There is some incertitude, however, regarding the extrapolation of rodent spatial navigation strategies to primates. Here we present an entirely new platform for investigating real spatial navigation in rhesus monkeys. We showed that monkeys can learn a pathway by using different strategies. In these experiments three monkeys learned to drive the wheelchair and to follow a specified route through a real maze. After learning the route, probe tests revealed that animals successively use three distinct navigation strategies based on i) the place of the reward, ii) the direction taken to obtain reward or iii) a cue indicating reward location. The strategy used depended of the options proposed and the duration of learning. This study reveals that monkeys, like rodents and humans, switch between different spatial navigation strategies with extended practice, implying well-conserved brain learning systems across different species. This new task with freely driving monkeys provides a good support for the electrophysiological and pharmacological investigation of spatial navigation in the real world by making possible electrophysiological and pharmacological investigations.

  14. microRNA-128a dysregulation in transgenic Huntington’s disease monkeys

    Science.gov (United States)

    2014-01-01

    Background Huntington’s Disease (HD) is a progressive neurodegenerative disorder with a single causal mutation in the Huntingtin (HTT) gene. MicroRNAs (miRNAs) have recently been implicated as epigenetic regulators of neurological disorders, however, their role in HD pathogenesis is not well defined. Here we study transgenic HD monkeys (HD monkeys) to examine miRNA dysregulation in a primate model of the disease. Results In this report, 11 miRNAs were found to be significantly associated (P value monkeys. We further focused on one of those candidates, miR-128a, due to the corresponding disruption in humans and mice with HD as well as its intriguing lists of gene targets. miR-128a was downregulated in our HD monkey model by the time of birth. We then confirmed that miR-128a was also downregulated in the brains of pre-symptomatic and post-symptomatic HD patients. Additionally, our studies confirmed a panel of canonical HD signaling genes regulated by miR-128a, including HTT and Huntingtin Interaction Protein 1 (HIP1). Conclusion Our studies found that miR-128a may play a critical role in HD and could be a viable candidate as a therapeutic or biomarker of the disease. PMID:24929669

  15. Evaluation of monkey intraocular pressure by rebound tonometer

    Science.gov (United States)

    Yu, Wenhan; Cao, Guiqun; Qiu, Jinghua; Ma, Jia; Li, Ni; Yu, Man; Yan, Naihong; Chen, Lei; Pang, Iok-Hou

    2009-01-01

    Purpose To evaluate the usefulness of the TonoVet™ rebound tonometer in measuring intraocular pressure (IOP) of monkeys. Methods The accuracy of the TonoVet™ rebound tonometer was determined in cannulated eyes of anesthetized rhesus monkeys where IOP was controlled by adjusting the height of a connected perfusate reservoir. To assess the applicability of the equipment through in vivo studies, the diurnal fluctuation of IOP and effects of IOP-lowering compounds were evaluated in monkeys. Results IOP readings generated by the TonoVet™ tonometer correlated very well with the actual pressure in the cannulated monkey eye. The linear correlation had a slope of 0.922±0.014 (mean±SEM, n=4), a y-intercept of 3.04±0.61, and a correlation coefficient of r2=0.97. Using this method, diurnal IOP fluctuation of the rhesus monkey was demonstrated. The tonometer was also able to detect IOP changes induced by pharmacologically active compounds. A single topical ocular instillation (15 μg) of the rho kinase inhibitor, H1152, produced a 5–6 mmHg reduction (pmonkey eye. PMID:19898690

  16. Distribution of corticotropin-releasing factor receptors in primate brain

    International Nuclear Information System (INIS)

    Millan, M.A.; Jacobowitz, D.M.; Hauger, R.L.; Catt, K.J.; Aguilera, G.

    1986-01-01

    The distribution and properties of receptors for corticotropin-releasing factor (CRF) were analyzed in the brain of cynomolgus monkeys. Binding of [ 125 I]tyrosine-labeled ovine CRF to frontal cortex and amygdala membrane-rich fractions was saturable, specific, and time- and temperature-dependent, reaching equilibrium in 30 min at 23 0 C. Scatchard analysis of the binding data indicated one class of high-affinity sites with a K/sub d/ of 1 nM and a concentration of 125 fmol/mg. As in the rat pituitary and brain, CRF receptors in monkey cerebral cortex and amygdala were coupled to adenylate cyclase. Autoradiographic analysis of specific CRF binding in brain sections revealed that the receptors were widely distributed in the cerebral cortex and limbic system. Receptor density was highest in the pars tuberalis of the pituitary and throughout the cerebral cortex, specifically in the prefrontal, frontal, orbital, cingulate, insular, and temporal areas, and in the cerebellar cortex. A low binding density was present in the superior colliculus, locus coeruleus, substantia gelatinosa, preoptic area, septal area, and bed nucleus of the stria terminalis. These data demonstrate that receptors for CRF are present within the primate brain at areas related to the central control of visceral function and behavior, suggesting that brain CRF may serve as a neurotransmitter in the coordination of endocrine and neural mechanisms involved in the response to stress

  17. Rhesus monkey neural stem cell transplantation promotes neural regeneration in rats with hippocampal lesions

    Directory of Open Access Journals (Sweden)

    Li-juan Ye

    2016-01-01

    Full Text Available Rhesus monkey neural stem cells are capable of differentiating into neurons and glial cells. Therefore, neural stem cell transplantation can be used to promote functional recovery of the nervous system. Rhesus monkey neural stem cells (1 × 105 cells/μL were injected into bilateral hippocampi of rats with hippocampal lesions. Confocal laser scanning microscopy demonstrated that green fluorescent protein-labeled transplanted cells survived and grew well. Transplanted cells were detected at the lesion site, but also in the nerve fiber-rich region of the cerebral cortex and corpus callosum. Some transplanted cells differentiated into neurons and glial cells clustering along the ventricular wall, and integrated into the recipient brain. Behavioral tests revealed that spatial learning and memory ability improved, indicating that rhesus monkey neural stem cells noticeably improve spatial learning and memory abilities in rats with hippocampal lesions.

  18. Psychophysical chromatic mechanisms in macaque monkey.

    Science.gov (United States)

    Stoughton, Cleo M; Lafer-Sousa, Rosa; Gagin, Galina; Conway, Bevil R

    2012-10-24

    Chromatic mechanisms have been studied extensively with psychophysical techniques in humans, but the number and nature of the mechanisms are still controversial. Appeals to monkey neurophysiology are often used to sort out the competing claims and to test hypotheses arising from the experiments in humans, but psychophysical chromatic mechanisms have never been assessed in monkeys. Here we address this issue by measuring color-detection thresholds in monkeys before and after chromatic adaptation, employing a standard approach used to determine chromatic mechanisms in humans. We conducted separate experiments using adaptation configured as either flickering full-field colors or heterochromatic gratings. Full-field colors would favor activity within the visual system at or before the arrival of retinal signals to V1, before the spatial transformation of color signals by the cortex. Conversely, gratings would favor activity within the cortex where neurons are often sensitive to spatial chromatic structure. Detection thresholds were selectively elevated for the colors of full-field adaptation when it modulated along either of the two cardinal chromatic axes that define cone-opponent color space [L vs M or S vs (L + M)], providing evidence for two privileged cardinal chromatic mechanisms implemented early in the visual-processing hierarchy. Adaptation with gratings produced elevated thresholds for colors of the adaptation regardless of its chromatic makeup, suggesting a cortical representation comprised of multiple higher-order mechanisms each selective for a different direction in color space. The results suggest that color is represented by two cardinal channels early in the processing hierarchy and many chromatic channels in brain regions closer to perceptual readout.

  19. Spatial Attention and Temporal Expectation Under Timed Uncertainty Predictably Modulate Neuronal Responses in Monkey V1

    Science.gov (United States)

    Sharma, Jitendra; Sugihara, Hiroki; Katz, Yarden; Schummers, James; Tenenbaum, Joshua; Sur, Mriganka

    2015-01-01

    The brain uses attention and expectation as flexible devices for optimizing behavioral responses associated with expected but unpredictably timed events. The neural bases of attention and expectation are thought to engage higher cognitive loci; however, their influence at the level of primary visual cortex (V1) remains unknown. Here, we asked whether single-neuron responses in monkey V1 were influenced by an attention task of unpredictable duration. Monkeys covertly attended to a spot that remained unchanged for a fixed period and then abruptly disappeared at variable times, prompting a lever release for reward. We show that monkeys responded progressively faster and performed better as the trial duration increased. Neural responses also followed monkey's task engagement—there was an early, but short duration, response facilitation, followed by a late but sustained increase during the time monkeys expected the attention spot to disappear. This late attentional modulation was significantly and negatively correlated with the reaction time and was well explained by a modified hazard function. Such bimodal, time-dependent changes were, however, absent in a task that did not require explicit attentional engagement. Thus, V1 neurons carry reliable signals of attention and temporal expectation that correlate with predictable influences on monkeys' behavioral responses. PMID:24836689

  20. The effects of passive humidifier dead space on respiratory variables in paralyzed and spontaneously breathing patients.

    Science.gov (United States)

    Campbell, R S; Davis, K; Johannigman, J A; Branson, R D

    2000-03-01

    Passive humidifiers have gained acceptance in the intensive care unit because of their low cost, simple operation, and elimination of condensate from the breathing circuit. However, the additional dead space of these devices may adversely affect respiratory function in certain patients. This study evaluates the effects of passive humidifier dead space on respiratory function. Two groups of patients were studied. The first group consisted of patients recovering from acute lung injury and breathing spontaneously on pressure support ventilation. The second group consisted of patients who were receiving controlled mechanical ventilation and were chemically paralyzed following operative procedures. All patients used 3 humidification devices in random order for one hour each. The devices were a heated humidifier (HH), a hygroscopic heat and moisture exchanger (HHME) with a dead space of 28 mL, and a heat and moisture exchanger (HME) with a dead space of 90 mL. During each measurement period the following were recorded: tidal volume, minute volume, respiratory frequency, oxygen consumption, carbon dioxide production, ratio of dead space volume to tidal volume (VD/VT), and blood gases. In the second group, intrinsic positive end-expiratory pressure was also measured. Addition of either of the passive humidifiers was associated with increased VD/VT. In spontaneously breathing patients, VD/VT increased from 59 +/- 13 (HH) to 62 +/- 13 (HHME) to 68 +/- 11% (HME) (p < 0.05). In these patients, constant alveolar ventilation was maintained as a result of increased respiratory frequency, from 22.1 +/- 6.6 breaths/min (HH) to 24.5 +/- 6.9 breaths/min (HHME) to 27.7 +/- 7.4 breaths/min (HME) (p < 0.05), and increased minute volume, from 9.1 +/- 3.5 L/min (HH) to 9.9 +/- 3.6 L/min (HHME) to 11.7 +/- 4.2 L/min (HME) (p < 0.05). There were no changes in blood gases or carbon dioxide production. In the paralyzed patient group, VD/VT increased from 54 +/- 12% (HH) to 56 +/- 10% (HHME

  1. Genome Editing of Monkey.

    Science.gov (United States)

    Liu, Zhen; Cai, Yijun; Sun, Qiang

    2017-01-01

    Gene-modified monkey models would be particularly valuable in biomedical and neuroscience research. Virus-based transgenic and programmable nucleases-based site-specific gene editing methods (TALEN, CRISPR-cas9) enable the generation of gene-modified monkeys with gain or loss of function of specific genes. Here, we describe the generation of transgenic and knock-out (KO) monkeys with high efficiency by lentivirus and programmable nucleases.

  2. A Brain–Spinal Interface Alleviating Gait Deficits after Spinal Cord Injury in Primates

    Science.gov (United States)

    Capogrosso, Marco; Milekovic, Tomislav; Borton, David; Wagner, Fabien; Moraud, Eduardo Martin; Mignardot, Jean-Baptiste; Buse, Nicolas; Gandar, Jerome; Barraud, Quentin; Xing, David; Rey, Elodie; Duis, Simone; Jianzhong, Yang; Ko, Wai Kin D.; Li, Qin; Detemple, Peter; Denison, Tim; Micera, Silvestro; Bezard, Erwan; Bloch, Jocelyne; Courtine, Grégoire

    2016-01-01

    Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain–computer interfaces1–3 have directly linked cortical activity to electrical stimulation of muscles, which have restored grasping abilities after hand paralysis1,4. Theoretically, this strategy could also restore control over leg muscle activity for walking5. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges6,7. Recently, we showed in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion8–10. Here, we interfaced leg motor cortex activity with epidural electrical stimulation protocols to establish a brain–spinal interface that alleviated gait deficits after a spinal cord injury in nonhuman primates. Rhesus monkeys were implanted with an intracortical microelectrode array into the leg area of motor cortex; and a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain–spinal interface in intact monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain–spinal interface restored weight-bearing locomotion of the paralyzed leg on a treadmill and overground. The implantable components integrated in the brain–spinal interface have all been approved for investigational

  3. On the role of emerging voluntary control of vocalization in language evolution. Comment on "Towards a Computational Comparative Neuroprimatology: Framing the language-ready brain" by Michael A. Arbib

    Science.gov (United States)

    Coudé, Gino

    2016-03-01

    This comment will be focused on the role of monkey vocal control in the evolution of language. I will essentially reiterate the observations expressed in a commentary [1] about the book ;How the brain got language: the mirror system hypothesis;, written by Arbib [2]. I will hopefully clarify our suggestion that non-human primates vocal communication, in conjunction with gestures, could have had an active role in the emergence of the first voluntary forms of utterances that will later shape protospeech. This suggestion is mainly rooted in neurophysiological data about vocal control in monkey. I will very briefly summarize how neurophysiological data allowed us to suggest a possible role for monkey vocalization in language evolution. We conducted a study [3] in which we recorded from ventral premotor cortex (PMv) of macaques trained to emit vocalizations (i.e. coo-calls). The results showed that the rostro-lateral part of PMv contains neurons that fire during conditioned vocalization. The involvement of PMv in vocalization production was further supported by electrical microstimulation of the cortical sector where some of the vocalization neurons were found. Microstimulation elicited in some cases a combination of jaw, tongue and larynx movements. To us, the evolutionary implications of those results were obvious: a partial voluntary vocal control was already taking place in the primate PMv cortex some 25 million years ago.

  4. Neurotoxic response of infant monkeys to methylmercury

    Energy Technology Data Exchange (ETDEWEB)

    Willes, R.F.; Truelove, J.F.; Nera, E.A.

    1978-02-01

    Four infant monkeys were dosed orally with 500 ..mu..g Hg/kg body wt./day (as methylmercury (MeHg) chloride dissolved sodium carbonate) beginning at 1 day of age. Neurological and behavioral signs of MeHg toxicity and blood Hg levels were monitored weekly. At first sign of MeHg intoxication, dosing with MeHg was terminated and the infants were monitored to assess reversal of the signs of MeHg toxicity. The first signs of MeHg toxicity, exhibited as a loss in dexterity and locomotor ability, were observed after 28 to 29 days of treatment; the blood Hg levels were 8.0 to 9.4 ..mu..g Hg/g blood. Dosing was terminated at 28 to 29 days of treatment but the signs of MeHg toxicity continued to develop. The infants became ataxic, blind, comatose and were necropsied at 35 to 43 days after initiating treatment with MgHg. The mercury concentrations in tissues analyzed after necropsy were highest in liver followed by occipital cortex and renal cortex. The mean blood/brain ratio was 0.21 +- 0.4. Histopathologic lesions were marked in the cerebrum with less severe lesions in the cerebellar nuclei. The Purkinje and granular cells of the cerebellar vermis appeared histologically normal. Lesions were not observed in the peripheral nervous system. The signs of MeHg intoxication, the tissue distribution of MeHg and histopathologic lesions observed in the infant monkeys were similar to those reported for adult monkeys.

  5. Newly Identified CYP2C93 Is a Functional Enzyme in Rhesus Monkey, but Not in Cynomolgus Monkey

    OpenAIRE

    Uno, Yasuhiro; Uehara, Shotaro; Kohara, Sakae; Iwasaki, Kazuhide; Nagata, Ryoichi; Fukuzaki, Koichiro; Utoh, Masahiro; Murayama, Norie; Yamazaki, Hiroshi

    2011-01-01

    Cynomolgus monkey and rhesus monkey are used in drug metabolism studies due to their evolutionary closeness and physiological resemblance to human. In cynomolgus monkey, we previously identified cytochrome P450 (P450 or CYP) 2C76 that does not have a human ortholog and is partly responsible for species differences in drug metabolism between cynomolgus monkey and human. In this study, we report characterization of CYP2C93 cDNA newly identified in cynomolgus monkey and rhesus monkey. The CYP2C9...

  6. Late effects of whole brain irradiation within the therapeutic range

    International Nuclear Information System (INIS)

    Caveness, W.F.; Carsten, A.L.

    1978-01-01

    Whole brain exposure with supervoltage x irradiation was carried out in three sets of Macaca mulatta. Two sets of 12 monkeys each, at puberty, received single and fractionated exposures, respectively. One set of 21 monkeys in adulthood received a fractionated exposure. Exposure to 1000 rads in a single dose, at puberty, caused no late effects. Exposure to 1500 rads caused small areas of necrosis in the forebrain white matter at 26 weeks, but a much more extensive involvement at and beyond 52 weeks that included confluent areas of necrosis in gray and white matter. Brain loss resulted in ventricular dilatation. Gliomas appeared in two out of three monkeys at or beyond 52 weeks. Exposure to 2000 rads caused such a wide scatter of focal areas of necrosis, including those in the brain stem, that survival beyond 20 to 26 weeks was not possible. All showed enlarged ventricular systems. Whole brain exposure, 200 rads a day, five days a week, for a course of 4000 rads, at puberty, resulted in no delayed effects. Whole brain exposure to 6000 rads in a six weeks course, in the adult, produced less effects than the same dose at puberty. The onset of the scattered necrotic lesions was later than expected, appearing in one out of three animals at 33 weeks, two out of three animals at 52 weeks, and two out of three at 104 weeks. The lesions at 104 weeks were predominantly mineralized, but were accompanied by a greater extent of telangiectasia than seen in the pubescent monkeys

  7. A 4-channel 3 Tesla phased array receive coil for awake rhesus monkey fMRI and diffusion MRI experiments.

    Science.gov (United States)

    Khachaturian, Mark Haig

    2010-01-01

    Awake monkey fMRI and diffusion MRI combined with conventional neuroscience techniques has the potential to study the structural and functional neural network. The majority of monkey fMRI and diffusion MRI experiments are performed with single coils which suffer from severe EPI distortions which limit resolution. By constructing phased array coils for monkey MRI studies, gains in SNR and anatomical accuracy (i.e., reduction of EPI distortions) can be achieved using parallel imaging. The major challenges associated with constructing phased array coils for monkeys are the variation in head size and space constraints. Here, we apply phased array technology to a 4-channel phased array coil capable of improving the resolution and image quality of full brain awake monkey fMRI and diffusion MRI experiments. The phased array coil is that can adapt to different rhesus monkey head sizes (ages 4-8) and fits in the limited space provided by monkey stereotactic equipment and provides SNR gains in primary visual cortex and anatomical accuracy in conjunction with parallel imaging and improves resolution in fMRI experiments by a factor of 2 (1.25 mm to 1.0 mm isotropic) and diffusion MRI experiments by a factor of 4 (1.5 mm to 0.9 mm isotropic).

  8. Object permanence in orangutans (Pongo pygmaeus) and squirrel monkeys (Saimiri sciureus).

    Science.gov (United States)

    de Blois, S T; Novak, M A; Bond, M

    1998-06-01

    The authors tested orangutans (Pongo pygmaeus) and squirrel monkeys (Saimiri sciureus) on object permanence tasks. In Experiment 1, orangutans solved all visible displacements and most invisible displacements except those involving movements into 2 boxes successively. In Experiment 2, performance of orangutans on double invisible displacements and control displacements (assessing simple strategies) was compared. Orangutans did not use the simple strategy of selecting the box visited last by the experimenter. Instead, poorer performance on double invisible displacements may have been related to increased memory requirements. In Experiment 3, squirrel monkeys were tested using the procedure of Experiment 1. Squirrel monkeys solved visible but did not comprehend invisible displacements. Results suggest that orangutans but not squirrel monkeys possess Stage 6 object permanence capabilities.

  9. Face Pareidolia in the Rhesus Monkey.

    Science.gov (United States)

    Taubert, Jessica; Wardle, Susan G; Flessert, Molly; Leopold, David A; Ungerleider, Leslie G

    2017-08-21

    Face perception in humans and nonhuman primates is rapid and accurate [1-4]. In the human brain, a network of visual-processing regions is specialized for faces [5-7]. Although face processing is a priority of the primate visual system, face detection is not infallible. Face pareidolia is the compelling illusion of perceiving facial features on inanimate objects, such as the illusory face on the surface of the moon. Although face pareidolia is commonly experienced by humans, its presence in other species is unknown. Here we provide evidence for face pareidolia in a species known to possess a complex face-processing system [8-10]: the rhesus monkey (Macaca mulatta). In a visual preference task [11, 12], monkeys looked longer at photographs of objects that elicited face pareidolia in human observers than at photographs of similar objects that did not elicit illusory faces. Examination of eye movements revealed that monkeys fixated the illusory internal facial features in a pattern consistent with how they view photographs of faces [13]. Although the specialized response to faces observed in humans [1, 3, 5-7, 14] is often argued to be continuous across primates [4, 15], it was previously unclear whether face pareidolia arose from a uniquely human capacity. For example, pareidolia could be a product of the human aptitude for perceptual abstraction or result from frequent exposure to cartoons and illustrations that anthropomorphize inanimate objects. Instead, our results indicate that the perception of illusory facial features on inanimate objects is driven by a broadly tuned face-detection mechanism that we share with other species. Published by Elsevier Ltd.

  10. Performance norms for a rhesus monkey neuropsychological testing battery: acquisition and long-term performance.

    Science.gov (United States)

    Weed, M R; Taffe, M A; Polis, I; Roberts, A C; Robbins, T W; Koob, G F; Bloom, F E; Gold, L H

    1999-10-25

    A computerized behavioral battery based upon human neuropsychological tests (CANTAB, CeNeS, Cambridge, UK) has been developed to assess cognitive behaviors of rhesus monkeys. Monkeys reliably performed multiple tasks, providing long-term assessment of changes in a number of behaviors for a given animal. The overall goal of the test battery is to characterize changes in cognitive behaviors following central nervous system (CNS) manipulations. The battery addresses memory (delayed non-matching to sample, DNMS; spatial working memory, using a self-ordered spatial search task, SOSS), attention (intra-/extra-dimensional shift, ID/ED), motivation (progressive-ratio, PR), reaction time (RT) and motor coordination (bimanual task). As with human neuropsychological batteries, different tasks are thought to involve different neural substrates, and therefore performance profiles should assess function in particular brain regions. Monkeys were tested in transport cages, and responding on a touch sensitive computer monitor was maintained by food reinforcement. Parametric manipulations of several tasks demonstrated the sensitivity of performance to increases in task difficulty. Furthermore, the factors influencing difficulty for rhesus monkeys were the same as those shown to affect human performance. Data from this study represent performance of a population of healthy normal monkeys that will be used for comparison in subsequent studies of performance following CNS manipulations such as infection with simian immunodeficiency virus (NeuroAIDS) or drug administration.

  11. Electrical Microstimulation of the Superior Colliculus in Strabismic Monkeys.

    Science.gov (United States)

    Fleuriet, Jérome; Walton, Mark M G; Ono, Seiji; Mustari, Michael J

    2016-06-01

    Visually guided saccades are disconjugate in human and nonhuman strabismic primates. The superior colliculus (SC) is a region of the brain topographically organized in visual and motor maps where the saccade goal is spatially coded. The present study was designed to investigate if a site of stimulation on the topographic motor map was evoking similar or different saccade vectors for each eye. We used microelectrical stimulation (MS) of the SC in two strabismic (one esotrope and one exotrope) and two control macaques under binocular and monocular viewing conditions. We compared the saccade amplitudes and directions for each SC site and each condition independently of the fixating eye and then between each fixating eye. A comparison with disconjugacies of visually guided saccades was also performed. We observed different saccade vectors for the two eyes in strabismic monkeys, but conjugate saccades in normal monkeys. Evoked saccade vectors for the left eye when that eye was fixating the target were different from those of the right eye when it was fixating. The disconjugacies evoked by the MS were not identical but similar to those observed for visually guided saccades especially for the dominant eye. Our results suggest that, in strabismus, the saccade generator does not interpret activation of a single location of the SC as the same desired displacement for each eye. This finding is important for advancing understanding of the development of neural circuits in strabismus. French Abstract.

  12. Optimal feedback control successfully explains changes in neural modulations during experiments with brain-machine interfaces

    Directory of Open Access Journals (Sweden)

    Miriam eZacksenhouse

    2015-05-01

    Full Text Available Recent experiments with brain-machine-interfaces (BMIs indicate that the extent of neural modulations increased abruptly upon starting to operate the interface, and especially after the monkey stopped moving its hand. In contrast, neural modulations that are correlated with the kinematics of the movement remained relatively unchanged. Here we demonstrate that similar changes are produced by simulated neurons that encode the relevant signals generated by an optimal feedback controller during simulated BMI experiments. The optimal feedback controller relies on state estimation that integrates both visual and proprioceptive feedback with prior estimations from an internal model. The processing required for optimal state estimation and control were conducted in the state-space, and neural recording was simulated by modeling two populations of neurons that encode either only the estimated state or also the control signal. Spike counts were generated as realizations of doubly stochastic Poisson processes with linear tuning curves. The model successfully reconstructs the main features of the kinematics and neural activity during regular reaching movements. Most importantly, the activity of the simulated neurons successfully reproduces the observed changes in neural modulations upon switching to brain control. Further theoretical analysis and simulations indicate that increasing the process noise during normal reaching movement results in similar changes in neural modulations. Thus we conclude that the observed changes in neural modulations during BMI experiments can be attributed to increasing process noise associated with the imperfect BMI filter, and, more directly, to the resulting increase in the variance of the encoded signals associated with state estimation and the required control signal.

  13. Optimal feedback control successfully explains changes in neural modulations during experiments with brain-machine interfaces.

    Science.gov (United States)

    Benyamini, Miri; Zacksenhouse, Miriam

    2015-01-01

    Recent experiments with brain-machine-interfaces (BMIs) indicate that the extent of neural modulations increased abruptly upon starting to operate the interface, and especially after the monkey stopped moving its hand. In contrast, neural modulations that are correlated with the kinematics of the movement remained relatively unchanged. Here we demonstrate that similar changes are produced by simulated neurons that encode the relevant signals generated by an optimal feedback controller during simulated BMI experiments. The optimal feedback controller relies on state estimation that integrates both visual and proprioceptive feedback with prior estimations from an internal model. The processing required for optimal state estimation and control were conducted in the state-space, and neural recording was simulated by modeling two populations of neurons that encode either only the estimated state or also the control signal. Spike counts were generated as realizations of doubly stochastic Poisson processes with linear tuning curves. The model successfully reconstructs the main features of the kinematics and neural activity during regular reaching movements. Most importantly, the activity of the simulated neurons successfully reproduces the observed changes in neural modulations upon switching to brain control. Further theoretical analysis and simulations indicate that increasing the process noise during normal reaching movement results in similar changes in neural modulations. Thus, we conclude that the observed changes in neural modulations during BMI experiments can be attributed to increasing process noise associated with the imperfect BMI filter, and, more directly, to the resulting increase in the variance of the encoded signals associated with state estimation and the required control signal.

  14. Old world monkeys compare to apes in the primate cognition test battery.

    Directory of Open Access Journals (Sweden)

    Vanessa Schmitt

    Full Text Available Understanding the evolution of intelligence rests on comparative analyses of brain sizes as well as the assessment of cognitive skills of different species in relation to potential selective pressures such as environmental conditions and social organization. Because of the strong interest in human cognition, much previous work has focused on the comparison of the cognitive skills of human toddlers to those of our closest living relatives, i.e. apes. Such analyses revealed that apes and children have relatively similar competencies in the physical domain, while human children excel in the socio-cognitive domain; in particular in terms of attention sharing, cooperation, and mental state attribution. To develop a full understanding of the evolutionary dynamics of primate intelligence, however, comparative data for monkeys are needed. We tested 18 Old World monkeys (long-tailed macaques and olive baboons in the so-called Primate Cognition Test Battery (PCTB (Herrmann et al. 2007, Science. Surprisingly, our tests revealed largely comparable results between Old World monkeys and the Great apes. Single comparisons showed that chimpanzees performed only better than the macaques in experiments on spatial understanding and tool use, but in none of the socio-cognitive tasks. These results question the clear-cut relationship between cognitive performance and brain size and--prima facie--support the view of an accelerated evolution of social intelligence in humans. One limitation, however, is that the initial experiments were devised to tap into human specific skills in the first place, thus potentially underestimating both true nonhuman primate competencies as well as species differences.

  15. Peripheral refraction in normal infant rhesus monkeys

    Science.gov (United States)

    Hung, Li-Fang; Ramamirtham, Ramkumar; Huang, Juan; Qiao-Grider, Ying; Smith, Earl L.

    2008-01-01

    Purpose To characterize peripheral refractions in infant monkeys. Methods Cross-sectional data for horizontal refractions were obtained from 58 normal rhesus monkeys at 3 weeks of age. Longitudinal data were obtained for both the vertical and horizontal meridians from 17 monkeys. Refractive errors were measured by retinoscopy along the pupillary axis and at eccentricities of 15, 30, and 45 degrees. Axial dimensions and corneal power were measured by ultrasonography and keratometry, respectively. Results In infant monkeys, the degree of radial astigmatism increased symmetrically with eccentricity in all meridians. There were, however, initial nasal-temporal and superior-inferior asymmetries in the spherical-equivalent refractive errors. Specifically, the refractions in the temporal and superior fields were similar to the central ametropia, but the refractions in the nasal and inferior fields were more myopic than the central ametropia and the relative nasal field myopia increased with the degree of central hyperopia. With age, the degree of radial astigmatism decreased in all meridians and the refractions became more symmetrical along both the horizontal and vertical meridians; small degrees of relative myopia were evident in all fields. Conclusions As in adult humans, refractive error varied as a function of eccentricity in infant monkeys and the pattern of peripheral refraction varied with the central refractive error. With age, emmetropization occurred for both central and peripheral refractive errors resulting in similar refractions across the central 45 degrees of the visual field, which may reflect the actions of vision-dependent, growth-control mechanisms operating over a wide area of the posterior globe. PMID:18487366

  16. Single subcutaneous dosing of cefovecin in rhesus monkeys (Macaca mulatta)

    DEFF Research Database (Denmark)

    Bakker, J.; Thuesen, Line Risager; Braskamp, G.

    2011-01-01

    was to determine whether cefovecin is a suitable antibiotic to prevent skin wound infection in rhesus monkeys. Therefore, the pharmacokinetics (PK) of cefovecin after a single subcutaneous injection at 8 mg/kg bodyweight in four rhesus monkeys (Macaca mulatta) and sensitivity of bacterial isolates from fresh skin...... wounds were determined. After administration, blood, urine, and feces were collected, and concentrations of cefovecin were determined. Further, the minimum inhibitory concentrations (MIC) for bacteria isolated from fresh skin wounds of monkeys during a health control program were determined. The mean...... maximum plasma concentration (C(max) ) of cefovecin was 78 µg/mL and was achieved after 57 min. The mean apparent long elimination half-life (t½) was 6.6 h and excretion occurred mainly via urine. The MIC for the majority of the bacteria examined was >100 µg/mL. The PK of cefovecin in rhesus monkeys...

  17. Late effects of whole brain irradiation within the therapeutic range

    International Nuclear Information System (INIS)

    Caveness, W.F.; Carsten, A.L.

    1978-01-01

    Whole brain exposure with supervoltage irradiation was carried out on three sets of Macaca mulatta. Two sets of 12 monkeys each, at puberty, received single and fractionated exposures respectively. One set of 21 monkeys in adulthood received a fractionated exposure. Exposure to 1000 rads in a single dose, at puberty, caused no late effects. Exposure to 1500 rads caused small areas of necrosis in the forebrain white matter at 26 weeks, but a much more extensive involvementat and beyond 52 weeks that included confluent areas of necrosis in gray and white matter. Brain loss resulted in ventricular dilatation. Gliomas appeared in two out of three monkeys at or beyond 52 weeks. Exposure to 2000 rads caused such a wide scatter of focal areas of necrosis, including those in the brain stem, that survival beyond 20-26 weeks was not possible. All showed enlarged ventricular systems. Whole brain exposure, 200 rads a day, five days a week, for a course of 4000 rads, at puberty, resulted in no delayed effects. An exposure to 6000 rads, in a six weeks course, caused small, less than 1 mm, widely scattered necrotic lesions with a predilection for the forebrain white matter but not excluding the central gray matter and brain stem, at 26 weeks. At 52 weeks, there was considerable mineralization of the lesions and widespread telangiectasia. In the developing lesions, multiple minute breaks in the blood brain barrier caused diffuse brain swelling, reflected by papilloedema. Whole brain exposure to 6000 rads in a six weeks course, in the adult, produced less effects than the same dose at puberty. The onset of the scattered necrotic lesions was later than expected, appearing in one out of three animals at 33 weeks, two out of three animals at 52 weeks, and two out of three at 104 weeks. The lesions at 104 weeks were predominantly mineralized, but were accompanied by a greater extent of telangiectasia than seen in the pubescent monkeys

  18. Synthesis, characterization, and first successful monkey imaging studies of metabotropic glutamate receptor subtype 5 (mGluR5) PET radiotracers.

    Science.gov (United States)

    Hamill, Terence G; Krause, Stephen; Ryan, Christine; Bonnefous, Celine; Govek, Steve; Seiders, T Jon; Cosford, Nicholas D P; Roppe, Jeffrey; Kamenecka, Ted; Patel, Shil; Gibson, Raymond E; Sanabria, Sandra; Riffel, Kerry; Eng, Waisi; King, Christopher; Yang, Xiaoqing; Green, Mitchell D; O'Malley, Stacey S; Hargreaves, Richard; Burns, H Donald

    2005-06-15

    Three metabotropic glutamate receptor subtype 5 (mGluR5) PET tracers have been labeled with either carbon-11 or fluorine-18 and their in vitro and in vivo behavior in rhesus monkey has been characterized. Each of these tracers share the common features of high affinity for mGluR5 (0.08-0.23 nM vs. rat mGluR5) and moderate lipophilicity (log P 2.8-3.4). Compound 1b was synthesized using a Suzuki or Stille coupling reaction with [11C]MeI. Compounds 2b and 3b were synthesized by a SNAr reaction using a 3-chlorobenzonitrile precursor. Autoradiographic studies in rhesus monkey brain slices using 2b and 3b showed specific binding in cortex, caudate, putamen, amygdala, hippocampus, most thalamic nuclei, and lower binding in the cerebellum. PET imaging studies in monkey showed that all three tracers readily enter the brain and provide an mGluR5-specific signal in all gray matter regions, including the cerebellum. The specific signal observed in the cerebellum was confirmed by the autoradiographic studies and saturation binding experiments that showed tracer binding in the cerebellum of rhesus monkeys. In vitro metabolism studies using the unlabeled compounds showed that 1a, 2a, and 3a are metabolized slower by human liver microsomes than by monkey liver microsomes. In vivo metabolism studies showed 3b to be long-lived in rhesus plasma with only one other more polar metabolite observed. (c) 2005 Wiley-Liss, Inc.

  19. Effects of social reorganization on dopamine D2/D3 receptor availability and cocaine self-administration in male cynomolgus monkeys.

    Science.gov (United States)

    Czoty, P W; Gould, R W; Gage, H D; Nader, M A

    2017-09-01

    Studies have demonstrated that brain dopamine D2/D3 receptors (D2/D3R) and the reinforcing effects of cocaine can be influenced by a monkey's position in the social dominance hierarchy. In this study, we manipulated the social ranks of monkeys by reorganizing social groups and assessed effects on D2/D3R availability and cocaine self-administration. Male cynomolgus monkeys (N = 12) had been trained to self-administer cocaine under a concurrent cocaine-food reinforcement schedule. Previously, PET measures of D2/D3R availability in the caudate nucleus and putamen had been obtained with [ 18 F]fluoroclebopride during cocaine abstinence, while monkeys lived in stable social groups of four monkeys/pen. For this study, monkeys were reorganized into groups that consisted of (1) four previously dominant, (2) four previously subordinate, and (3) a mix of previously dominant and subordinate monkeys. After 3 months, D2/D3R availability was redetermined and cocaine self-administration was reexamined. D2/D3R availability significantly increased after reorganization in monkeys who were formerly subordinate, with the greatest increases observed in those that became dominant. No consistent changes in D2/D3R availability were observed in formerly dominant monkeys. Cocaine self-administration did not vary according to rank after reorganization of social groups. However, when compared to their previous cocaine self-administration data, the potency of cocaine as a reinforcer decreased in 9 of 11 monkeys. These results indicate that changing the social conditions can alter D2/D3R availability in subordinate monkeys in a manner suggestive of environmental enrichment. In most monkeys, social reorganization shifted the cocaine dose-response curve to the right, also consistent with environmental enrichment.

  20. The effect of angiotensin receptor neprilysin inhibitor, sacubitril/valsartan, on central nervous system amyloid-β concentrations and clearance in the cynomolgus monkey.

    Science.gov (United States)

    Schoenfeld, Heidi A; West, Tim; Verghese, Philip B; Holubasch, Mary; Shenoy, Neeta; Kagan, David; Buono, Chiara; Zhou, Wei; DeCristofaro, Marc; Douville, Julie; Goodrich, Geoffrey G; Mansfield, Keith; Saravanan, Chandra; Cumin, Frederic; Webb, Randy L; Bateman, Randall J

    2017-05-15

    Sacubitril/valsartan (LCZ696) is the first angiotensin receptor neprilysin inhibitor approved to reduce cardiovascular mortality and hospitalization in patients with heart failure with reduced ejection fraction. As neprilysin (NEP) is one of several enzymes known to degrade amyloid-β (Aβ), there is a theoretical risk of Aβ accumulation following long-term NEP inhibition. The primary objective of this study was to evaluate the potential effects of sacubitril/valsartan on central nervous system clearance of Aβ isoforms in cynomolgus monkeys using the sensitive Stable Isotope Labeling Kinetics (SILK™)-Aβ methodology. The in vitro selectivity of valsartan, sacubitril, and its active metabolite sacubitrilat was established; sacubitrilat did not inhibit other human Aβ-degrading metalloproteases. In a 2-week study, sacubitril/valsartan (50mg/kg/day) or vehicle was orally administered to female cynomolgus monkeys in conjunction with SILK™-Aβ. Despite low cerebrospinal fluid (CSF) and brain penetration, CSF exposure to sacubitril was sufficient to inhibit NEP and resulted in an increase in the elimination half-life of Aβ1-42 (65.3%; p=0.026), Aβ1-40 (35.2%; p=0.04) and Aβtotal (29.8%; p=0.04) acutely; this returned to normal as expected with repeated dosing for 15days. CSF concentrations of newly generated Aβ (AUC (0-24h) ) indicated elevations in the more aggregable form Aβ1-42 on day 1 (20.4%; p=0.039) and day 15 (34.7%; p=0.0003) and in shorter forms Aβ1-40 (23.4%; p=0.009), Aβ1-38 (64.1%; p=0.0001) and Aβtotal (50.45%; p=0.00002) on day 15. However, there were no elevations in any Aβ isoforms in the brains of these monkeys on day 16. In a second study cynomolgus monkeys were administered sacubitril/valsartan (300mg/kg) or vehicle control for 39weeks; no microscopic brain changes or Aβ deposition, as assessed by immunohistochemical staining, were present. Further clinical studies are planned to address the relevance of these findings. Copyright

  1. Radiation damage to the normal monkey brain. Experimental study induced by interstitial irradiation

    International Nuclear Information System (INIS)

    Mishima, Nobuya; Tamiya, Takashi; Matsumoto, Kengo; Furuta, Tomohisa; Ohmoto, Takashi

    2003-01-01

    Radiation damage to normal brain tissue induced by interstitial irradiation with iridium-192 seeds was sequentially evaluated by computed tomography (CT), magnetic resonance imaging (MRI), and histological examination. This study was carried out in 14 mature Japanese monkeys. The experimental area received more than 200-260 Gy of irradiation developed coagulative necrosis. Infiltration of macrophages to the periphery of the necrotic area was seen. In addition, neovascularization, hyalinization of vascular walls, and gliosis were found in the periphery of the area invaded by the macrophages. All sites at which the vascular walls were found to have acute stage fibrinoid necrosis eventually developed coagulative necrosis. The focus of necrosis was detected by MRI starting 1 week after the end of radiation treatment, and the size of the necrotic area did not change for 6 months. The peripheral areas showed clear ring enhancement with contrast material. Edema surrounding the lesions was the most significant 1 week after radiation and was reduced to a minimum level 1 month later. However, the edema then expanded once again and was sustained for as long as 6 months. CT did not provide as clear of a presentation as MRI, but it did reveal similar findings for the most part, and depicted calcification in the necrotic area. This experimental model is considered useful for conducting basic research on brachytherapy, as well as for achieving a better understanding of delayed radiation necrosis. (author)

  2. Ethical aspects of brain computer interfaces: a scoping review

    OpenAIRE

    Burwell, Sasha; Sample, Matthew; Racine, Eric

    2017-01-01

    Background Brain-Computer Interface (BCI) is a set of technologies that are of increasing interest to researchers. BCI has been proposed as assistive technology for individuals who are non-communicative or paralyzed, such as those with amyotrophic lateral sclerosis or spinal cord injury. The technology has also been suggested for enhancement and entertainment uses, and there are companies currently marketing BCI devices for those purposes (e.g., gaming) as well as health-related purposes (e.g...

  3. Sporadic Premature Aging in a Japanese Monkey: A Primate Model for Progeria

    Science.gov (United States)

    Oishi, Takao; Imai, Hiroo; Go, Yasuhiro; Imamura, Masanori; Hirai, Hirohisa; Takada, Masahiko

    2014-01-01

    In our institute, we have recently found a child Japanese monkey who is characterized by deep wrinkles of the skin and cataract of bilateral eyes. Numbers of analyses were performed to identify symptoms representing different aspects of aging. In this monkey, the cell cycle of fibroblasts at early passage was significantly extended as compared to a normal control. Moreover, both the appearance of senescent cells and the deficiency in DNA repair were observed. Also, pathological examination showed that this monkey has poikiloderma with superficial telangiectasia, and biochemical assay confirmed that levels of HbA1c and urinary hyaluronan were higher than those of other (child, adult, and aged) monkey groups. Of particular interest was that our MRI analysis revealed expansion of the cerebral sulci and lateral ventricles probably due to shrinkage of the cerebral cortex and the hippocampus. In addition, the conduction velocity of a peripheral sensory but not motor nerve was lower than in adult and child monkeys, and as low as in aged monkeys. However, we could not detect any individual-unique mutations of known genes responsible for major progeroid syndromes. The present results indicate that the monkey suffers from a kind of progeria that is not necessarily typical to human progeroid syndromes. PMID:25365557

  4. Noninvasive scalp recording of cortical auditory evoked potentials in the alert macaque monkey.

    Science.gov (United States)

    Itoh, Kosuke; Nejime, Masafumi; Konoike, Naho; Nakada, Tsutomu; Nakamura, Katsuki

    2015-09-01

    Scalp-recorded evoked potentials (EP) provide researchers and clinicians with irreplaceable means for recording stimulus-related neural activities in the human brain, due to its high temporal resolution, handiness, and, perhaps more importantly, non-invasiveness. This work recorded the scalp cortical auditory EP (CAEP) in unanesthetized monkeys by using methods that are essentially identical to those applied to humans. Young adult rhesus monkeys (Macaca mulatta, 5-7 years old) were seated in a monkey chair, and their head movements were partially restricted by polystyrene blocks and tension poles placed around their head. Individual electrodes were fixated on their scalp using collodion according to the 10-20 system. Pure tone stimuli were presented while electroencephalograms were recorded from up to nineteen channels, including an electrooculogram channel. In all monkeys (n = 3), the recorded CAEP comprised a series of positive and negative deflections, labeled here as macaque P1 (mP1), macaque N1 (mN1), macaque P2 (mP2), and macaque N2 (mN2), and these transient responses to sound onset were followed by a sustained potential that continued for the duration of the sound, labeled the macaque sustained potential (mSP). mP1, mN2 and mSP were the prominent responses, and they had maximal amplitudes over frontal/central midline electrode sites, consistent with generators in auditory cortices. The study represents the first noninvasive scalp recording of CAEP in alert rhesus monkeys, to our knowledge. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. A real-time brain-machine interface combining motor target and trajectory intent using an optimal feedback control design.

    Directory of Open Access Journals (Sweden)

    Maryam M Shanechi

    Full Text Available Real-time brain-machine interfaces (BMI have focused on either estimating the continuous movement trajectory or target intent. However, natural movement often incorporates both. Additionally, BMIs can be modeled as a feedback control system in which the subject modulates the neural activity to move the prosthetic device towards a desired target while receiving real-time sensory feedback of the state of the movement. We develop a novel real-time BMI using an optimal feedback control design that jointly estimates the movement target and trajectory of monkeys in two stages. First, the target is decoded from neural spiking activity before movement initiation. Second, the trajectory is decoded by combining the decoded target with the peri-movement spiking activity using an optimal feedback control design. This design exploits a recursive Bayesian decoder that uses an optimal feedback control model of the sensorimotor system to take into account the intended target location and the sensory feedback in its trajectory estimation from spiking activity. The real-time BMI processes the spiking activity directly using point process modeling. We implement the BMI in experiments consisting of an instructed-delay center-out task in which monkeys are presented with a target location on the screen during a delay period and then have to move a cursor to it without touching the incorrect targets. We show that the two-stage BMI performs more accurately than either stage alone. Correct target prediction can compensate for inaccurate trajectory estimation and vice versa. The optimal feedback control design also results in trajectories that are smoother and have lower estimation error. The two-stage decoder also performs better than linear regression approaches in offline cross-validation analyses. Our results demonstrate the advantage of a BMI design that jointly estimates the target and trajectory of movement and more closely mimics the sensorimotor control system.

  6. Fast optical signal not detected in awake behaving monkeys.

    Science.gov (United States)

    Radhakrishnan, Harsha; Vanduffel, Wim; Deng, Hong Ping; Ekstrom, Leeland; Boas, David A; Franceschini, Maria Angela

    2009-04-01

    While the ability of near-infrared spectroscopy (NIRS) to measure cerebral hemodynamic evoked responses (slow optical signal) is well established, its ability to measure non-invasively the 'fast optical signal' is still controversial. Here, we aim to determine the feasibility of performing NIRS measurements of the 'fast optical signal' or Event-Related Optical Signals (EROS) under optimal experimental conditions in awake behaving macaque monkeys. These monkeys were implanted with a 'recording well' to expose the dura above the primary visual cortex (V1). A custom-made optical probe was inserted and fixed into the well. The close proximity of the probe to the brain maximized the sensitivity to changes in optical properties in the cortex. Motion artifacts were minimized by physical restraint of the head. Full-field contrast-reversing checkerboard stimuli were presented to monkeys trained to perform a visual fixation task. In separate sessions, two NIRS systems (CW4 and ISS FD oximeter), which previously showed the ability to measure the fast signal in human, were used. In some sessions EEG was acquired simultaneously with the optical signal. The increased sensitivity to cortical optical changes with our experimental setup was quantified with 3D Monte Carlo simulations on a segmented MRI monkey head. Averages of thousands of stimuli in the same animal, or grand averages across the two animals and across repeated sessions, did not lead to detection of the fast optical signal using either amplitude or phase of the optical signal. Hemodynamic responses and visual evoked potentials were instead always detected with single trials or averages of a few stimuli. Based on these negative results, despite the optimal experimental conditions, we doubt the usefulness of non-invasive fast optical signal measurements with NIRS.

  7. The calcium endocrine system of adolescent rhesus monkeys and controls before and after spaceflight

    Science.gov (United States)

    Arnaud, Sara B.; Navidi, Meena; Deftos, Leonard; Thierry-Palmer, Myrtle; Dotsenko, Rita; Bigbee, Allison; Grindeland, Richard E.

    2002-01-01

    The calcium endocrine system of nonhuman primates can be influenced by chairing for safety and the weightless environment of spaceflight. The serum of two rhesus monkeys flown on the Bion 11 mission was assayed pre- and postflight for vitamin D metabolites, parathyroid hormone, calcitonin, parameters of calcium homeostasis, cortisol, and indexes of renal function. Results were compared with the same measures from five monkeys before and after chairing for a flight simulation study. Concentrations of 1,25-dihydroxyvitamin D were 72% lower after the flight than before, and more than after chairing on the ground (57%, P endocrine system were similar to the effects of chairing on the ground, but were more pronounced. Reduced intestinal calcium absorption, losses in body weight, increases in cortisol, and higher postflight blood urea nitrogen were the changes in flight monkeys that distinguished them from the flight simulation study animals.

  8. Experimental test of spatial updating models for monkey eye-head gaze shifts.

    Directory of Open Access Journals (Sweden)

    Tom J Van Grootel

    Full Text Available How the brain maintains an accurate and stable representation of visual target locations despite the occurrence of saccadic gaze shifts is a classical problem in oculomotor research. Here we test and dissociate the predictions of different conceptual models for head-unrestrained gaze-localization behavior of macaque monkeys. We adopted the double-step paradigm with rapid eye-head gaze shifts to measure localization accuracy in response to flashed visual stimuli in darkness. We presented the second target flash either before (static, or during (dynamic the first gaze displacement. In the dynamic case the brief visual flash induced a small retinal streak of up to about 20 deg at an unpredictable moment and retinal location during the eye-head gaze shift, which provides serious challenges for the gaze-control system. However, for both stimulus conditions, monkeys localized the flashed targets with accurate gaze shifts, which rules out several models of visuomotor control. First, these findings exclude the possibility that gaze-shift programming relies on retinal inputs only. Instead, they support the notion that accurate eye-head motor feedback updates the gaze-saccade coordinates. Second, in dynamic trials the visuomotor system cannot rely on the coordinates of the planned first eye-head saccade either, which rules out remapping on the basis of a predictive corollary gaze-displacement signal. Finally, because gaze-related head movements were also goal-directed, requiring continuous access to eye-in-head position, we propose that our results best support a dynamic feedback scheme for spatial updating in which visuomotor control incorporates accurate signals about instantaneous eye- and head positions rather than relative eye- and head displacements.

  9. Reproductive function of monkeys subjected to chronic irradiation

    International Nuclear Information System (INIS)

    Artem'eva, N.S.; Kosichenko, L.P.; Andreeva, A.V.; Zvereva, G.A.

    1976-01-01

    Marked functional disorders have been detected in reproductive glands of eight female monkeys (as compared to twelve control animals) subjected to protracted (up to eight years) irradiation (cumulative doses 826-3282 R). Irradiated monkeys exhibited a drastically decreased reproductive capacity, early menopause and sterility. Irradiation of preadolescent animals inhibited, in most cases, the puberty processes and disturbed sex cycles. Structural disorders in sex glands, inhibition of the processes of maturation and ovulation of folloculi, death of the mass of germ cells, atypical vegetations of the integmentary epithelium, sclerosing and cystic degeneration of the glandular tissue have been revealed

  10. [Monkey-pox, a model of emergent then reemergent disease].

    Science.gov (United States)

    Georges, A J; Matton, T; Courbot-Georges, M C

    2004-01-01

    The recent emergence of monkey pox in the United States of America highlights the problem (known for other infectious agents) of dissemination of pathogens outside their endemic area, and of subsequent global threats of variable gravity according to agents. It is a real emergency since monkey pox had been confined to Africa for several decades, where small epidemics occurred from time to time, monkey pox is a "miniature smallpox" which, in Africa, evolves on an endemic (zoonotic) mode with, as reservoirs, several species of wild rodents (mainly squirrels) and some monkey species. It can be accidentally transmitted to man then develops as epidemics, sometimes leading to death. The virus was imported in 2003 in the United States of America, via Gambia rats and wild squirrels (all African species), and infected prairie dogs (which are now in fashion as pets), then crossed the species barrier to man. In the United States of America, screening campaigns, epidemiological investigations, and subsequent treatments led to a rapid control of the epidemic, which is a model of emergent disease for this country. Therapeutic and preventive measures directly applicable to monkey pox are discussed. They can also be applied against other pox virus infections (including smallpox). The risk of criminal introduction of pox viruses is discussed since it is, more than ever, a real worldwide threat.

  11. Thermoregulatory Responses of Febrile Monkeys During Microwave Exposure

    National Research Council Canada - National Science Library

    Adair, E

    1997-01-01

    .... In a controlled ambient temperature of 26 degrees C, autonomic mechanisms of heat production and heat loss were measured in febrile squirrel monkeys during 30-min exposures to 450 or 2450 MHz CW MW...

  12. Vicarious learning from human models in monkeys.

    Science.gov (United States)

    Falcone, Rossella; Brunamonti, Emiliano; Genovesio, Aldo

    2012-01-01

    We examined whether monkeys can learn by observing a human model, through vicarious learning. Two monkeys observed a human model demonstrating an object-reward association and consuming food found underneath an object. The monkeys observed human models as they solved more than 30 learning problems. For each problem, the human models made a choice between two objects, one of which concealed a piece of apple. In the test phase afterwards, the monkeys made a choice of their own. Learning was apparent from the first trial of the test phase, confirming the ability of monkeys to learn by vicarious observation of human models.

  13. Decoder calibration with ultra small current sample set for intracortical brain-machine interface

    Science.gov (United States)

    Zhang, Peng; Ma, Xuan; Chen, Luyao; Zhou, Jin; Wang, Changyong; Li, Wei; He, Jiping

    2018-04-01

    Objective. Intracortical brain-machine interfaces (iBMIs) aim to restore efficient communication and movement ability for paralyzed patients. However, frequent recalibration is required for consistency and reliability, and every recalibration will require relatively large most current sample set. The aim in this study is to develop an effective decoder calibration method that can achieve good performance while minimizing recalibration time. Approach. Two rhesus macaques implanted with intracortical microelectrode arrays were trained separately on movement and sensory paradigm. Neural signals were recorded to decode reaching positions or grasping postures. A novel principal component analysis-based domain adaptation (PDA) method was proposed to recalibrate the decoder with only ultra small current sample set by taking advantage of large historical data, and the decoding performance was compared with other three calibration methods for evaluation. Main results. The PDA method closed the gap between historical and current data effectively, and made it possible to take advantage of large historical data for decoder recalibration in current data decoding. Using only ultra small current sample set (five trials of each category), the decoder calibrated using the PDA method could achieve much better and more robust performance in all sessions than using other three calibration methods in both monkeys. Significance. (1) By this study, transfer learning theory was brought into iBMIs decoder calibration for the first time. (2) Different from most transfer learning studies, the target data in this study were ultra small sample set and were transferred to the source data. (3) By taking advantage of historical data, the PDA method was demonstrated to be effective in reducing recalibration time for both movement paradigm and sensory paradigm, indicating a viable generalization. By reducing the demand for large current training data, this new method may facilitate the application

  14. Newly identified CYP2C93 is a functional enzyme in rhesus monkey, but not in cynomolgus monkey.

    Directory of Open Access Journals (Sweden)

    Yasuhiro Uno

    Full Text Available Cynomolgus monkey and rhesus monkey are used in drug metabolism studies due to their evolutionary closeness and physiological resemblance to human. In cynomolgus monkey, we previously identified cytochrome P450 (P450 or CYP 2C76 that does not have a human ortholog and is partly responsible for species differences in drug metabolism between cynomolgus monkey and human. In this study, we report characterization of CYP2C93 cDNA newly identified in cynomolgus monkey and rhesus monkey. The CYP2C93 cDNA contained an open reading frame of 490 amino acids approximately 84-86% identical to human CYP2Cs. CYP2C93 was located in the genomic region, which corresponded to the intergenic region in the human genome, indicating that CYP2C93 does not correspond to any human genes. CYP2C93 mRNA was expressed predominantly in the liver among 10 tissues analyzed. The CYP2C93 proteins heterologously expressed in Escherichia coli metabolized human CYP2C substrates, diclofenac, flurbiprofen, paclitaxel, S-mephenytoin, and tolbutamide. In addition to a normal transcript (SV1, an aberrantly spliced transcript (SV2 lacking exon 2 was identified, which did not give rise to a functional protein due to frameshift and a premature termination codon. Mini gene assay revealed that the genetic variant IVS2-1G>T at the splice site of intron 1, at least partly, accounted for the exon-2 skipping; therefore, this genotype would influence CYP2C93-mediated drug metabolism. SV1 was expressed in 6 of 11 rhesus monkeys and 1 of 8 cynomolgus monkeys, but the SV1 in the cynomolgus monkey was nonfunctional due to a rare null genotype (c.102T>del. These results suggest that CYP2C93 can play roles as a drug-metabolizing enzyme in rhesus monkeys (not in cynomolgus monkeys, although its relative contribution to drug metabolism has yet to be validated.

  15. Postmortem changes in the neuroanatomical characteristics of the primate brain: hippocampal formation.

    Science.gov (United States)

    Lavenex, Pierre; Lavenex, Pamela Banta; Bennett, Jeffrey L; Amaral, David G

    2009-01-01

    Comparative studies of the structural organization of the brain are fundamental to our understanding of human brain function. However, whereas brains of experimental animals are fixed by perfusion of a fixative through the vasculature, human or ape brains are fixed by immersion after varying postmortem intervals. Although differential treatments might affect the fundamental characteristics of the tissue, this question has not been evaluated empirically in primate brains. Monkey brains were either perfused or acquired after varying postmortem intervals before immersion-fixation in 4% paraformaldehyde. We found that the fixation method affected the neuroanatomical characteristics of the monkey hippocampal formation. Soma size was smaller in Nissl-stained, immersion-fixed tissue, although overall brain volume was larger as compared to perfusion-fixed tissue. Nonphosphorylated high-molecular-weight neurofilament immunoreactivity was lower in CA3 pyramidal neurons, dentate mossy cells, and the entorhinal cortex, whereas it was higher in the mossy fiber pathway in immersion-fixed tissue. Serotonin-immunoreactive fibers were well stained in perfused tissue but were undetectable in immersion-fixed tissue. Although regional immunoreactivity patterns for calcium-binding proteins were not affected, intracellular staining degraded with increasing postmortem intervals. Somatostatin-immunoreactive clusters of large axonal varicosities, previously reported only in humans, were observed in immersion-fixed monkey tissue. In addition, calretinin-immunoreactive multipolar neurons, previously observed only in rodents, were found in the rostral dentate gyrus in both perfused and immersion-fixed brains. In conclusion, comparative studies of the brain must evaluate the effects of fixation on the staining pattern of each marker in every structure of interest before drawing conclusions about species differences.

  16. Responses of squirrel monkeys to their experimentally modified mobbing calls

    Science.gov (United States)

    Fichtel, Claudia; Hammerschmidt, Kurt

    2003-05-01

    Previous acoustic analyses suggested emotion-correlated changes in the acoustic structure of squirrel monkey (Saimiri sciureus) vocalizations. Specifically, calls given in aversive contexts were characterized by an upward shift in frequencies, often accompanied by an increase in amplitude. In order to test whether changes in frequencies or amplitude are indeed relevant for conspecific listeners, playback experiments were conducted in which either frequencies or amplitude of mobbing calls were modified. Latency and first orienting response were measured in playback experiments with six adult squirrel monkeys. After broadcasting yaps with increased frequencies or amplitude, squirrel monkeys showed a longer orienting response towards the speaker than after the corresponding control stimuli. Furthermore, after broadcasting yaps with decreased frequencies or amplitude, squirrel monkeys showed a shorter orienting response towards the speaker than after the corresponding manipulated calls with higher frequencies or amplitude. These results suggest that changes in frequencies or amplitude were perceived by squirrel monkeys, indicating that the relationship between call structure and the underlying affective state of the caller agreed with the listener's assessment of the calls. However, a simultaneous increase in frequencies and amplitude did not lead to an enhanced response, compared to each single parameter. Thus, from the receiver's perspective, both call parameters may mutually replace each other.

  17. The Peptide Vaccine Combined with Prior Immunization of a Conventional Diphtheria-Tetanus Toxoid Vaccine Induced Amyloid β Binding Antibodies on Cynomolgus Monkeys and Guinea Pigs

    Directory of Open Access Journals (Sweden)

    Akira Yano

    2015-01-01

    Full Text Available The reduction of brain amyloid beta (Aβ peptides by anti-Aβ antibodies is one of the possible therapies for Alzheimer’s disease. We previously reported that the Aβ peptide vaccine including the T-cell epitope of diphtheria-tetanus combined toxoid (DT induced anti-Aβ antibodies, and the prior immunization with conventional DT vaccine enhanced the immunogenicity of the peptide. Cynomolgus monkeys were given the peptide vaccine subcutaneously in combination with the prior DT vaccination. Vaccination with a similar regimen was also performed on guinea pigs. The peptide vaccine induced anti-Aβ antibodies in cynomolgus monkeys and guinea pigs without chemical adjuvants, and excessive immune responses were not observed. Those antibodies could preferentially recognize Aβ40, and Aβ42 compared to Aβ fibrils. The levels of serum anti-Aβ antibodies and plasma Aβ peptides increased in both animals and decreased the brain Aβ40 level of guinea pigs. The peptide vaccine could induce a similar binding profile of anti-Aβ antibodies in cynomolgus monkeys and guinea pigs. The peptide vaccination could be expected to reduce the brain Aβ peptides and their toxic effects via clearance of Aβ peptides by generated antibodies.

  18. Habit learning and brain-machine interfaces (BMI): a tribute to Valentino Braitenberg's "Vehicles".

    Science.gov (United States)

    Birbaumer, Niels; Hummel, Friedhelm C

    2014-10-01

    Brain-Machine Interfaces (BMI) allow manipulation of external devices and computers directly with brain activity without involvement of overt motor actions. The neurophysiological principles of such robotic brain devices and BMIs follow Hebbian learning rules as described and realized by Valentino Braitenberg in his book "Vehicles," in the concept of a "thought pump" residing in subcortical basal ganglia structures. We describe here the application of BMIs for brain communication in totally locked-in patients and argue that the thought pump may extinguish-at least partially-in those people because of extinction of instrumentally learned cognitive responses and brain responses. We show that Pavlovian semantic conditioning may allow brain communication even in the completely paralyzed who does not show response-effect contingencies. Principles of skill learning and habit acquisition as formulated by Braitenberg are the building blocks of BMIs and neuroprostheses.

  19. Serotonin shapes risky decision making in monkeys.

    Science.gov (United States)

    Long, Arwen B; Kuhn, Cynthia M; Platt, Michael L

    2009-12-01

    Some people love taking risks, while others avoid gambles at all costs. The neural mechanisms underlying individual variation in preference for risky or certain outcomes, however, remain poorly understood. Although behavioral pathologies associated with compulsive gambling, addiction and other psychiatric disorders implicate deficient serotonin signaling in pathological decision making, there is little experimental evidence demonstrating a link between serotonin and risky decision making, in part due to the lack of a good animal model. We used dietary rapid tryptophan depletion (RTD) to acutely lower brain serotonin in three macaques performing a simple gambling task for fluid rewards. To confirm the efficacy of RTD experiments, we measured total plasma tryptophan using high-performance liquid chromatography (HPLC) with electrochemical detection. Reducing brain serotonin synthesis decreased preference for the safe option in a gambling task. Moreover, lowering brain serotonin function significantly decreased the premium required for monkeys to switch their preference to the risky option, suggesting that diminished serotonin signaling enhances the relative subjective value of the risky option. These results implicate serotonin in risk-sensitive decision making and, further, suggest pharmacological therapies for treating pathological risk preferences in disorders such as problem gambling and addiction.

  20. Vicarious learning from human models in monkeys.

    Directory of Open Access Journals (Sweden)

    Rossella Falcone

    Full Text Available We examined whether monkeys can learn by observing a human model, through vicarious learning. Two monkeys observed a human model demonstrating an object-reward association and consuming food found underneath an object. The monkeys observed human models as they solved more than 30 learning problems. For each problem, the human models made a choice between two objects, one of which concealed a piece of apple. In the test phase afterwards, the monkeys made a choice of their own. Learning was apparent from the first trial of the test phase, confirming the ability of monkeys to learn by vicarious observation of human models.

  1. Get the Monkey off Your Back

    Science.gov (United States)

    Ciabattini, David; Custer, Timothy J.

    2008-01-01

    Monkeys are the problems that need solutions, the tasks that need to be accomplished, the decisions that need to be made, and the actions that need to be taken. According to a theory, people carry monkeys around on their backs until they can successfully shift their burden to someone else and the monkey leaps from one back to the next. Managers…

  2. PhcrTx2, a New Crab-Paralyzing Peptide Toxin from the Sea Anemone Phymanthus crucifer

    Science.gov (United States)

    Garateix, Anoland; Salceda, Emilio; Zaharenko, André Junqueira; Pons, Tirso; Santos, Yúlica; Arreguín, Roberto; Ständker, Ludger; Forssmann, Wolf-Georg; Tytgat, Jan; Vega, Rosario

    2018-01-01

    Sea anemones produce proteinaceous toxins for predation and defense, including peptide toxins that act on a large variety of ion channels of pharmacological and biomedical interest. Phymanthus crucifer is commonly found in the Caribbean Sea; however, the chemical structure and biological activity of its toxins remain unknown, with the exception of PhcrTx1, an acid-sensing ion channel (ASIC) inhibitor. Therefore, in the present work, we focused on the isolation and characterization of new P. crucifer toxins by chromatographic fractionation, followed by a toxicity screening on crabs, an evaluation of ion channels, and sequence analysis. Five groups of toxic chromatographic fractions were found, and a new paralyzing toxin was purified and named PhcrTx2. The toxin inhibited glutamate-gated currents in snail neurons (maximum inhibition of 35%, IC50 4.7 µM), and displayed little or no influence on voltage-sensitive sodium/potassium channels in snail and rat dorsal root ganglion (DRG) neurons, nor on a variety of cloned voltage-gated ion channels. The toxin sequence was fully elucidated by Edman degradation. PhcrTx2 is a new β-defensin-fold peptide that shares a sequence similarity to type 3 potassium channels toxins. However, its low activity on the evaluated ion channels suggests that its molecular target remains unknown. PhcrTx2 is the first known paralyzing toxin in the family Phymanthidae. PMID:29414882

  3. PhcrTx2, a New Crab-Paralyzing Peptide Toxin from the Sea Anemone Phymanthus crucifer

    Directory of Open Access Journals (Sweden)

    Armando Alexei Rodríguez

    2018-02-01

    Full Text Available Sea anemones produce proteinaceous toxins for predation and defense, including peptide toxins that act on a large variety of ion channels of pharmacological and biomedical interest. Phymanthus crucifer is commonly found in the Caribbean Sea; however, the chemical structure and biological activity of its toxins remain unknown, with the exception of PhcrTx1, an acid-sensing ion channel (ASIC inhibitor. Therefore, in the present work, we focused on the isolation and characterization of new P. crucifer toxins by chromatographic fractionation, followed by a toxicity screening on crabs, an evaluation of ion channels, and sequence analysis. Five groups of toxic chromatographic fractions were found, and a new paralyzing toxin was purified and named PhcrTx2. The toxin inhibited glutamate-gated currents in snail neurons (maximum inhibition of 35%, IC50 4.7 µM, and displayed little or no influence on voltage-sensitive sodium/potassium channels in snail and rat dorsal root ganglion (DRG neurons, nor on a variety of cloned voltage-gated ion channels. The toxin sequence was fully elucidated by Edman degradation. PhcrTx2 is a new β-defensin-fold peptide that shares a sequence similarity to type 3 potassium channels toxins. However, its low activity on the evaluated ion channels suggests that its molecular target remains unknown. PhcrTx2 is the first known paralyzing toxin in the family Phymanthidae.

  4. Ethograms indicate stable well-being during prolonged training phases in rhesus monkeys used in neurophysiological research.

    Science.gov (United States)

    Hage, Steffen R; Ott, Torben; Eiselt, Anne-Kathrin; Jacob, Simon N; Nieder, Andreas

    2014-01-01

    Awake, behaving rhesus monkeys are widely used in neurophysiological research. Neural signals are typically measured from monkeys trained with operant conditioning techniques to perform a variety of behavioral tasks in exchange for rewards. Over the past years, monkeys' psychological well-being during experimentation has become an increasingly important concern. We suggest objective criteria to explore whether training sessions during which the monkeys work under controlled water intake over many days might affect their behavior. With that aim, we analyzed a broad range of species-specific behaviors over several months ('ethogram') and used these ethograms as a proxy for the monkeys' well-being. Our results show that monkeys' behavior during training sessions is unaffected by the duration of training-free days in-between. Independently of the number of training-free days (two or nine days) with ad libitum food and water supply, the monkeys were equally active and alert in their home group cages during training phases. This indicates that the monkeys were well habituated to prolonged working schedules and that their well-being was stably ensured during the training sessions.

  5. The biocompatibility, integrity, and positional stability of an injectable microstimulator for reanimation of the paralyzed larynx.

    Science.gov (United States)

    Zealear, D L; Garren, K C; Rodriguez, R J; Reyes, J H; Huang, S; Dokmeci, M R; Najafi, K

    2001-08-01

    The biocompatibility, integrity, positional stability, and potential use of hermetically sealed injectable wireless micromachined microstimulators were investigated for reanimation of the paralyzed larynx. The device, consisting of silicon and glass, has been tested and proven to be biocompatible with no evidence of pathological tissue reaction or rejection up to one-year implantation in the rat dorsum and canine larynx. By one month, each unit was encapsulated by a thin membrane, which thickened to form a fibrous layer of less than 500 microm at 6-12 months. The microstimulators demonstrated long-term in vivo durability: the hermetic seal of only one in ten devices was breached. Once implanted, migration of the device varied from 0 to 3 cm, depending upon the extent of surgical dissection. No discernable migration was noted when the tissue dissection was minimal. Studies utilizing a modified device equipped with electrodes indicated that migration was nominal with sufficient positional stability to ensure activation of target muscles for glottis opening. This study supported the feasibility of using a microstimulator for reanimation of paralyzed laryngeal muscles that open the airway during breathing. This innovative approach to treatment would alleviate the need for a tracheotomy or surgical resection of the vocal fold.

  6. Space representation for eye movements is more contralateral in monkeys than in humans

    OpenAIRE

    Kagan, Igor; Iyer, Asha; Lindner, Axel; Andersen, Richard A.

    2010-01-01

    Contralateral hemispheric representation of sensory inputs (the right visual hemifield in the left hemisphere and vice versa) is a fundamental feature of primate sensorimotor organization, in particular the visuomotor system. However, many higher-order cognitive functions in humans show an asymmetric hemispheric lateralization—e.g., right brain specialization for spatial processing—necessitating a convergence of information from both hemifields. Electrophysiological studies in monkeys and fun...

  7. Analysis of prostate-specific antigen transcripts in chimpanzees, cynomolgus monkeys, baboons, and African green monkeys.

    Directory of Open Access Journals (Sweden)

    James N Mubiru

    Full Text Available The function of prostate-specific antigen (PSA is to liquefy the semen coagulum so that the released sperm can fuse with the ovum. Fifteen spliced variants of the PSA gene have been reported in humans, but little is known about alternative splicing in nonhuman primates. Positive selection has been reported in sex- and reproductive-related genes from sea urchins to Drosophila to humans; however, there are few studies of adaptive evolution of the PSA gene. Here, using polymerase chain reaction (PCR product cloning and sequencing, we study PSA transcript variant heterogeneity in the prostates of chimpanzees (Pan troglodytes, cynomolgus monkeys (Macaca fascicularis, baboons (Papio hamadryas anubis, and African green monkeys (Chlorocebus aethiops. Six PSA variants were identified in the chimpanzee prostate, but only two variants were found in cynomolgus monkeys, baboons, and African green monkeys. In the chimpanzee the full-length transcript is expressed at the same magnitude as the transcripts that retain intron 3. We have found previously unidentified splice variants of the PSA gene, some of which might be linked to disease conditions. Selection on the PSA gene was studied in 11 primate species by computational methods using the sequences reported here for African green monkey, cynomolgus monkey, baboon, and chimpanzee and other sequences available in public databases. A codon-based analysis (dN/dS of the PSA gene identified potential adaptive evolution at five residue sites (Arg45, Lys70, Gln144, Pro189, and Thr203.

  8. Vicarious Learning from Human Models in Monkeys

    OpenAIRE

    Falcone, Rossella; Brunamonti, Emiliano; Genovesio, Aldo

    2012-01-01

    We examined whether monkeys can learn by observing a human model, through vicarious learning. Two monkeys observed a human model demonstrating an object-reward association and consuming food found underneath an object. The monkeys observed human models as they solved more than 30 learning problems. For each problem, the human models made a choice between two objects, one of which concealed a piece of apple. In the test phase afterwards, the monkeys made a choice of their own. Learning was app...

  9. Neurotoxic response of infant monkeys to methylmercury.

    Science.gov (United States)

    Willes, R F; Truelove, J F; Nera, E A

    1978-02-01

    Four infant monkeys were dosed orally with 500 microgram Hg/kg body wt./day /as methylmercury (MeHg) chloride dissolved sodium carbonate) beginning at 1 day of age. Neurological and behavioral signs of MeHg toxicity and blood Hg levels were monitored weekly. At first sign of MeHg intoxication, dosing with MeHg was terminated and the infants were monitored to assess reversal of the signs of MeHg toxicity. The first signs of MeHg toxicity, exhibited as a loss in dexterity and locomotor ability, were observed after 28--29 days of treatment; the blood Hg levels were 8.0--9.4 microgram Hg/g blood. Dosing was terminated at 28--29 days of treatment but the signs of MeHg toxicity continued to develop. The infants became ataxic, blind, comatose and were necropsied at 35--43 days after initiating treatment with MgHg. The mercury concentrations in tissues analyzed after necropsy were highest in liver (55.8 +/- 3.2 microgram Hg/g) followed by occipital cortex (35.6 +/- 4.8 microgram Hg/g) renal cortex (32.8 +/- 1.6 microgram Hg/g). The frontal and temporal cortices had 27.0 +/- 3.4 and 29.6 +/- 4.9 microgram Hg/g respectively while the cerebellar Hg concentration averaged 13.0 +/- 1.5 microgram Hg/g. The mean blood/brain ratio was 0.21 +/- 0.4. Histopathologic lesions were marked in the cerebrum with less severe lesions in the cerebellar nuclei. The Purkinje and granular cells of the cerebellar vermis appeared histologically normal. Lesions were not observed in the peripheral nervous system. The signs of MeHg intoxication, the tissue distribution of MeHg and histopathologic lesions observed in the infant monkeys were similar to those reported for adult monkeys.

  10. Recombinant human tripeptidyl peptidase-1 infusion to the monkey CNS: Safety, pharmacokinetics, and distribution

    Energy Technology Data Exchange (ETDEWEB)

    Vuillemenot, Brian R., E-mail: bvuillemenot@bmrn.com [BioMarin Pharmaceutical Inc., Novato, CA (United States); Kennedy, Derek [BioMarin Pharmaceutical Inc., Novato, CA (United States); Reed, Randall P.; Boyd, Robert B. [Northern Biomedical Research, Inc., Muskegon, MI (United States); Butt, Mark T. [Tox Path Specialists, LLC, Hagerstown, MD (United States); Musson, Donald G.; Keve, Steve; Cahayag, Rhea; Tsuruda, Laurie S.; O' Neill, Charles A. [BioMarin Pharmaceutical Inc., Novato, CA (United States)

    2014-05-15

    CLN2 disease is caused by deficiency in tripeptidyl peptidase-1 (TPP1), leading to neurodegeneration and death. The safety, pharmacokinetics (PK), and CNS distribution of recombinant human TPP1 (rhTPP1) were characterized following a single intracerebroventricular (ICV) or intrathecal-lumbar (IT-L) infusion to cynomolgus monkeys. Animals received 0, 5, 14, or 20 mg rhTPP1, ICV, or 14 mg IT-L, in artificial cerebrospinal fluid (aCSF) vehicle. Plasma and CSF were collected for PK analysis. Necropsies occurred at 3, 7, and 14 days post-infusion. CNS tissues were sampled for rhTPP1 distribution. TPP1 infusion was well tolerated and without effect on clinical observations or ECG. A mild increase in CSF white blood cells (WBCs) was detected transiently after ICV infusion. Isolated histological changes related to catheter placement and infusion were observed in ICV treated animals, including vehicle controls. The CSF and plasma exposure profiles were equivalent between animals that received an ICV or IT-L infusion. TPP1 levels peaked at the end of infusion, at which point the enzyme was present in plasma at 0.3% to 0.5% of CSF levels. TPP1 was detected in brain tissues with half-lives of 3–14 days. CNS distribution between ICV and IT-L administration was similar, although ICV resulted in distribution to deep brain structures including the thalamus, midbrain, and striatum. Direct CNS infusion of rhTPP1 was well tolerated with no drug related safety findings. The favorable nonclinical profile of ICV rhTPP1 supports the treatment of CLN2 by direct administration to the CNS. - Highlights: • TPP1 enzyme replacement therapy to the CNS is in development for CLN2 disease. • Toxicology, pharmacokinetics, and CNS distribution were assessed in monkeys. • TPP1 infusion directly to the brain did not result in any safety concerns. • A positive pharmacokinetic and distribution profile resulted from TPP1 infusion. • This study demonstrates the feasibility of ICV administered

  11. Recombinant human tripeptidyl peptidase-1 infusion to the monkey CNS: Safety, pharmacokinetics, and distribution

    International Nuclear Information System (INIS)

    Vuillemenot, Brian R.; Kennedy, Derek; Reed, Randall P.; Boyd, Robert B.; Butt, Mark T.; Musson, Donald G.; Keve, Steve; Cahayag, Rhea; Tsuruda, Laurie S.; O'Neill, Charles A.

    2014-01-01

    CLN2 disease is caused by deficiency in tripeptidyl peptidase-1 (TPP1), leading to neurodegeneration and death. The safety, pharmacokinetics (PK), and CNS distribution of recombinant human TPP1 (rhTPP1) were characterized following a single intracerebroventricular (ICV) or intrathecal-lumbar (IT-L) infusion to cynomolgus monkeys. Animals received 0, 5, 14, or 20 mg rhTPP1, ICV, or 14 mg IT-L, in artificial cerebrospinal fluid (aCSF) vehicle. Plasma and CSF were collected for PK analysis. Necropsies occurred at 3, 7, and 14 days post-infusion. CNS tissues were sampled for rhTPP1 distribution. TPP1 infusion was well tolerated and without effect on clinical observations or ECG. A mild increase in CSF white blood cells (WBCs) was detected transiently after ICV infusion. Isolated histological changes related to catheter placement and infusion were observed in ICV treated animals, including vehicle controls. The CSF and plasma exposure profiles were equivalent between animals that received an ICV or IT-L infusion. TPP1 levels peaked at the end of infusion, at which point the enzyme was present in plasma at 0.3% to 0.5% of CSF levels. TPP1 was detected in brain tissues with half-lives of 3–14 days. CNS distribution between ICV and IT-L administration was similar, although ICV resulted in distribution to deep brain structures including the thalamus, midbrain, and striatum. Direct CNS infusion of rhTPP1 was well tolerated with no drug related safety findings. The favorable nonclinical profile of ICV rhTPP1 supports the treatment of CLN2 by direct administration to the CNS. - Highlights: • TPP1 enzyme replacement therapy to the CNS is in development for CLN2 disease. • Toxicology, pharmacokinetics, and CNS distribution were assessed in monkeys. • TPP1 infusion directly to the brain did not result in any safety concerns. • A positive pharmacokinetic and distribution profile resulted from TPP1 infusion. • This study demonstrates the feasibility of ICV administered

  12. The protective influence of the locus ceruleus on the blood-brain barrier

    International Nuclear Information System (INIS)

    Harik, S.I.; McGunigal, T. Jr.

    1984-01-01

    The functions of the putative noradrenergic innervation of cerebral microvessels from the nucleus locus ceruleus remain ambiguous. Although most evidence indicates that such innervation does not have a major role in the control of cerebral blood flow, there are increasing indications that it modulates transport and permeability functions of the blood-brain barrier. In this study we investigated the effect of unilateral chemical lesioning of the locus ceruleus on the leakage of radioiodinated human serum albumin across the blood-brain barrier. Experiments were performed in awake and restrained rats under steady-state conditions and during drug-induced systemic arterial hypertension, and in anesthetized and paralyzed rats during bicuculline-induced seizures. Both hypertension and seizures are known to be associated with increased leakage of macromolecules across the blood-brain barrier. Albumin leakage into norepinephrine-depleted forebrain structures ipsilateral to the locus ceruleus lesion was compared with that of the contralateral side. There were no side-to-side differences in blood-brain barrier permeability to albumin under steady-state conditions, the stress of restraint, or angiotensin-induced hypertension, or after isoproterenol administration. Norepinephrine-induced hypertension and seizures, however, caused significant increases in albumin leakage into forebrain structures ipsilateral to the lesion. These results suggest that noradrenergic innervation of cerebral microvessels from the locus ceruleus helps preserve the integrity of the blood-brain barrier during pathophysiological states associated with hypertension and increased circulating catecholamines

  13. Autonomous replication of plasmids bearing monkey DNA origin-enriched sequences

    International Nuclear Information System (INIS)

    Frappier, L.; Zannis-Hadjopoulos, M.

    1987-01-01

    Twelve clones of origin-enriched sequences (ORS) isolated from early replicating monkey (CV-1) DNA were examined for transient episomal replication in transfected CV-1, COS-7, and HeLa cells. Plasmid DNA was isolated at time intervals after transfection and screened by the Dpn I resistance assay or by the bromodeoxyuridine substitution assay to differentiate between input and replicated DNA. The authors have identified four monkey ORS (ORS3, -8, -9, and -12) that can support plasmid replication in mammalian cells. This replication is carried out in a controlled and semiconservative manner characteristic of mammalian replicons. ORS replication was most efficient in HeLa cells. Electron microscopy showed ORS8 and ORS12 plasmids of the correct size with replication bubbles. Using a unique restriction site in ORS12, we have mapped the replication bubble within the monkey DNA sequence

  14. Standardized Full-Field Electroretinography in the Green Monkey (Chlorocebus sabaeus)

    DEFF Research Database (Denmark)

    Bouskila, Joseph; Javadi, Pasha; Palmour, Roberta M

    2014-01-01

    Full-field electroretinography is an objective measure of retinal function, serving as an important diagnostic clinical tool in ophthalmology for evaluating the integrity of the retina. Given the similarity between the anatomy and physiology of the human and Green Monkey eyes, this species has......). Photopic and scotopic ERG recordings were obtained by full-field stimulation over a range of 6 log units of intensity in dark-adapted or light-adapted eyes of adult Green Monkeys (Chlorocebus sabaeus). Intensity, duration, and interval of light stimuli were varied separately. Reproducible values...... of amplitude and latency were obtained for the a- and b-waves, under well-controlled adaptation and stimulus conditions; the i-wave was also easily identifiable and separated from the a-b-wave complex in the photopic ERG. The recordings obtained in the healthy Green Monkey matched very well with those...

  15. Canine distemper outbreak in rhesus monkeys, China.

    Science.gov (United States)

    Qiu, Wei; Zheng, Ying; Zhang, Shoufeng; Fan, Quanshui; Liu, Hua; Zhang, Fuqiang; Wang, Wei; Liao, Guoyang; Hu, Rongliang

    2011-08-01

    Since 2006, canine distemper outbreaks have occurred in rhesus monkeys at a breeding farm in Guangxi, People's Republic of China. Approximately 10,000 animals were infected (25%-60% disease incidence); 5%-30% of infected animals died. The epidemic was controlled by vaccination. Amino acid sequence analysis of the virus indicated a unique strain.

  16. Induction of encephalitis in rhesus monkeys infused with lymphocryptovirus-infected B-cells presenting MOG(34-56 peptide.

    Directory of Open Access Journals (Sweden)

    Krista G Haanstra

    Full Text Available The overlapping epidemiology of multiple sclerosis (MS and Epstein-Barr virus (EBV, the increased risk to develop MS after infectious mononucleosis (IM and the localization of EBV-infected B-cells within the MS brain suggest a causal link between EBV and MS. However, the underlying mechanism is unknown. We hypothesize that EBV-infected B-cells are capable of eliciting a central nervous system (CNS targeting autoimmune reaction. To test this hypothesis we have developed a novel experimental model in rhesus monkeys of IM-like disease induced by infusing autologous B-lymphoblastoid cells (B-LCL. Herpesvirus papio (HVP is a lymphocryptovirus related to EBV and was used to generate rhesus monkey B-LCL. Three groups of five animals were included; each group received three intravenous infusions of B-LCL that were either pulsed with the encephalitogenic self peptide MOG(34-56 (group A, a mimicry peptide (981-1003 of the major capsid protein of cytomegalovirus (CMVmcp(981-1003; group B or the citrullinated MOG(34-56 (cMOG(34-56; group C. Groups A and B received on day 98 a single immunization with MOG(34-56 in incomplete Freund's adjuvant (IFA. Group C monkeys were euthanized just prior to day 98 without booster immunization. We observed self-peptide-specific proliferation of T-cells, superimposed on similar strong proliferation of CD3(+CD8(+ T-cells against the B-LCL as observed in IM. The brains of several monkeys contained perivascular inflammatory lesions of variable size, comprising CD3(+ and CD68(+ cells. Moreover, clusters of CD3(+ and CD20(+ cells were detected in the meninges. The only evident clinical sign was substantial loss of bodyweight (>15%, a symptom observed both in early autoimmune encephalitis and IM. In conclusion, this model suggests that EBV-induced B-LCL can elicit a CNS targeting inflammatory (autoimmune reaction.

  17. What Do Monkey Calls Mean?

    Science.gov (United States)

    Schlenker, Philippe; Chemla, Emmanuel; Zuberbühler, Klaus

    2016-12-01

    A field of primate linguistics is gradually emerging. It combines general questions and tools from theoretical linguistics with rich data gathered in experimental primatology. Analyses of several monkey systems have uncovered very simple morphological and syntactic rules and have led to the development of a primate semantics that asks new questions about the division of semantic labor between the literal meaning of monkey calls, additional mechanisms of pragmatic enrichment, and the environmental context. We show that comparative studies across species may validate this program and may in some cases help in reconstructing the evolution of monkey communication over millions of years. Copyright © 2016. Published by Elsevier Ltd.

  18. Cyto-, myelo- and chemoarchitecture of the prefrontal cortex of the Cebus monkey

    Science.gov (United States)

    2011-01-01

    Background According to several lines of evidence, the great expansion observed in the primate prefrontal cortex (PfC) was accompanied by the emergence of new cortical areas during phylogenetic development. As a consequence, the structural heterogeneity noted in this region of the primate frontal lobe has been associated with diverse behavioral and cognitive functions described in human and non-human primates. A substantial part of this evidence was obtained using Old World monkeys as experimental model; while the PfC of New World monkeys has been poorly studied. In this study, the architecture of the PfC in five capuchin monkeys (Cebus apella) was analyzed based on four different architectonic tools, Nissl and myelin staining, histochemistry using the lectin Wisteria floribunda agglutinin and immunohistochemistry using SMI-32 antibody. Results Twenty-two architectonic areas in the Cebus PfC were distinguished: areas 8v, 8d, 9d, 12l, 45, 46v, 46d, 46vr and 46dr in the lateral PfC; areas 11l, 11m, 12o, 13l, 13m, 13i, 14r and 14c in the orbitofrontal cortex, with areas 14r and 14c occupying the ventromedial corner; areas 32r, 32c, 25 and 9m in the medial PfC, and area 10 in the frontal pole. This number is significantly higher than the four cytoarchitectonic areas previously recognized in the same species. However, the number and distribution of these areas in Cebus were to a large extent similar to those described in Old World monkeys PfC in more recent studies. Conclusions The present parcellation of the Cebus PfC considerably modifies the scheme initially proposed for this species but is in line with previous studies on Old World monkeys. Thus, it was observed that the remarkable anatomical similarity between the brains of genera Macaca and Cebus may extend to architectonic aspects. Since monkeys of both genera evolved independently over a long period of time facing different environmental pressures, the similarities in the architectonic maps of PfC in both genera

  19. Postmortem changes in the neuroanatomical characteristics of the primate brain: the hippocampal formation

    Science.gov (United States)

    Lavenex, Pierre; Lavenex, Pamela Banta; Bennett, Jeffrey L.; Amaral, David G.

    2009-01-01

    Comparative studies of the structural organization of the brain are fundamental to our understanding of human brain function. However, whereas brains of experimental animals are fixed by perfusion of a fixative through the vasculature, human or ape brains are fixed by immersion after varying postmortem intervals. Although differential treatments might affect the fundamental characteristics of the tissue, this question has not been evaluated empirically in primate brains. Monkey brains were either perfused, or acquired after varying postmortem intervals before immersion-fixation in 4% paraformaldehyde. We found that the fixation method affected the neuroanatomical characteristics of the monkey hippocampal formation. Soma size was smaller in Nissl-stained, immersion-fixed tissue, although overall brain volume was larger, as compared to perfusion-fixed tissue. Non-phosphorylated high-molecular-weight neurofilament immunoreactivity was lower in CA3 pyramidal neurons, dentate mossy cells and the entorhinal cortex, whereas it was higher in the mossy fiber pathway in immersion-fixed tissue. Serotonin-immunoreactive fibers were well-stained in perfused tissue but were undetectable in immersion-fixed tissue. Although regional immunoreactivity patterns for calcium-binding proteins were not affected, intracellular staining degraded with increasing postmortem intervals. Somatostatin-immunoreactive clusters of large axonal varicosities, previously reported only in humans, were observed in immersion-fixed monkey tissue. In addition, calretinin-immunoreactive multipolar neurons, previously observed only in rodents, were found in the rostral dentate gyrus in both perfused and immersion-fixed brains. In conclusion, comparative studies of the brain must evaluate the effects of fixation on the staining pattern of each marker in every structure of interest before drawing conclusions about species differences. PMID:18972553

  20. Self-Control and the Developing Brain

    Science.gov (United States)

    Tarullo, Amanda R.; Obradovic, Jelena; Gunnar, Megan R.

    2009-01-01

    Self-control is a skill that children need to succeed academically, socially, and emotionally. Brain regions essential to self-control are immature at birth and develop slowly throughout childhood. From ages 3 to 6 years, as these brain regions become more mature, children show improved ability to control impulses, shift their attention flexibly,…

  1. Epigenetic mechanism underlying the development of polycystic ovary syndrome (PCOS)-like phenotypes in prenatally androgenized rhesus monkeys.

    Science.gov (United States)

    Xu, Ning; Kwon, Soonil; Abbott, David H; Geller, David H; Dumesic, Daniel A; Azziz, Ricardo; Guo, Xiuqing; Goodarzi, Mark O

    2011-01-01

    The pathogenesis of polycystic ovary syndrome (PCOS) is poorly understood. PCOS-like phenotypes are produced by prenatal androgenization (PA) of female rhesus monkeys. We hypothesize that perturbation of the epigenome, through altered DNA methylation, is one of the mechanisms whereby PA reprograms monkeys to develop PCOS. Infant and adult visceral adipose tissues (VAT) harvested from 15 PA and 10 control monkeys were studied. Bisulfite treated samples were subjected to genome-wide CpG methylation analysis, designed to simultaneously measure methylation levels at 27,578 CpG sites. Analysis was carried out using Bayesian Classification with Singular Value Decomposition (BCSVD), testing all probes simultaneously in a single test. Stringent criteria were then applied to filter out invalid probes due to sequence dissimilarities between human probes and monkey DNA, and then mapped to the rhesus genome. This yielded differentially methylated loci between PA and control monkeys, 163 in infant VAT, and 325 in adult VAT (BCSVD Pexcess fetal androgen exposure in female nonhuman primates may predispose to PCOS via alteration of the epigenome, providing a novel avenue to understand PCOS in humans.

  2. Effects of heated hydrotherapy on muscle HSP70 and glucose metabolism in old and young vervet monkeys.

    Science.gov (United States)

    Kavanagh, Kylie; Davis, Ashely T; Jenkins, Kurt A; Flynn, D Mickey

    2016-07-01

    Increasing heat shock protein 70 (HSP70) in aged and/or insulin-resistant animal models confers benefits to healthspan and lifespan. Heat application to increase core temperature induces HSPs in metabolically important tissues, and preliminary human and animal data suggest that heated hydrotherapy is an effective method to achieve increased HSPs. However, safety concerns exist, particularly in geriatric medicine where organ and cardiovascular disease commonly will preexist. We evaluated young vervet monkeys compared to old, insulin-resistant vervet monkeys (Chlorocebus aethiops sabaeus) in their core temperatures, glucose tolerance, muscle HSP70 level, and selected safety biomarkers after 10 sessions of hot water immersions administered twice weekly. Hot water immersion robustly induced the heat shock response in muscles. We observed that heat-treated old and young monkeys have significantly higher muscle HSP70 than control monkeys and treatment was without significant adverse effects on organ or cardiovascular health. Heat therapy improved pancreatic responses to glucose challenge and tended to normalize glucose excursions. A trend for worsened blood pressure and glucose values in the control monkeys and improved values in heat-treated monkeys were seen to support further investigation into the safety and efficacy of this intervention for metabolic syndrome or diabetes in young or old persons unable to exercise.

  3. Restoration of motor function following spinal cord injury via optimal control of intraspinal microstimulation: toward a next generation closed-loop neural prosthesis.

    Directory of Open Access Journals (Sweden)

    Peter Jonas Grahn

    2014-09-01

    Full Text Available Movement is planned and coordinated by the brain and carried out by contracting muscles acting on specific joints. Motor commands initiated in the brain travel through descending pathways in the spinal cord to effector motor neurons before reaching target muscles. Damage to these pathways by spinal cord injury (SCI can result in paralysis below the injury level. However, the planning and coordination centers of the brain, as well as peripheral nerves and the muscles that they act upon, remain functional. Neuroprosthetic devices can restore motor function following SCI by direct electrical stimulation of the neuromuscular system. Unfortunately, conventional neuroprosthetic techniques are limited by a myriad of factors that include, but are not limited to, a lack of characterization of non-linear input/output system dynamics, mechanical coupling, limited number of degrees of freedom, high power consumption, large device size, and rapid onset of muscle fatigue. Wireless multi-channel closed-loop neuroprostheses that integrate command signals from the brain with sensor-based feedback from the environment and the system’s state offer the possibility of increasing device performance, ultimately improving quality of life for people with SCI. In this manuscript, we review neuroprosthetic technology for improving functional restoration following SCI and describe brain-machine interfaces suitable for control of neuroprosthetic systems with multiple degrees of freedom. Additionally, we discuss novel stimulation paradigms that can improve synergy with higher planning centers and improve fatigue-resistant activation of paralyzed muscles. In the near future, integration of these technologies will provide SCI survivors with versatile closed-loop neuroprosthetic systems for restoring function to paralyzed muscles.

  4. The effect of learning on the function of monkey extrastriate visual cortex.

    Directory of Open Access Journals (Sweden)

    Gregor Rainer

    2004-02-01

    Full Text Available One of the most remarkable capabilities of the adult brain is its ability to learn and continuously adapt to an ever-changing environment. While many studies have documented how learning improves the perception and identification of visual stimuli, relatively little is known about how it modifies the underlying neural mechanisms. We trained monkeys to identify natural images that were degraded by interpolation with visual noise. We found that learning led to an improvement in monkeys' ability to identify these indeterminate visual stimuli. We link this behavioral improvement to a learning-dependent increase in the amount of information communicated by V4 neurons. This increase was mediated by a specific enhancement in neural activity. Our results reveal a mechanism by which learning increases the amount of information that V4 neurons are able to extract from the visual environment. This suggests that V4 plays a key role in resolving indeterminate visual inputs by coordinated interaction between bottom-up and top-down processing streams.

  5. Lateralization for visual processes: eye preference in Campbell's monkeys (Cercopithecus c. campbelli).

    Science.gov (United States)

    Chapelain, Amandine S; Blois-Heulin, Catherine

    2009-01-01

    Brain lateralization has been the matter of extensive research over the last centuries, but it remains an unsolved issue. While hand preferences have been extensively studied, very few studies have investigated laterality of eye use in non-human primates. We examined eye preference in 14 Campbell's monkeys (Cercopithecus c. campbelli). We assessed eye preference to look at a seed placed inside a tube using monocular vision. Eye use was recorded for 100 independent and non-rewarded trials per individual. All of the 14 monkeys showed very strong preferences in the choice of the eye used to look inside the tube (mean preference: 97.6%). Eight subjects preferred the right eye and six subjects preferred the left eye. The results are discussed in light of previous data on eye preference in primates, and compared to data on hand preference from these subjects. Our findings would support the hypothesis for an early emergence of lateralization for perceptual processes compared to manual motor functions.

  6. Steroid metabolism by monkey and human spermatozoa

    International Nuclear Information System (INIS)

    Rajalakshmi, M.; Sehgal, A.; Pruthi, J.S.; Anand-Kumar, T.C.

    1983-01-01

    Freshly ejaculated spermatozoa from monkey and human were washed and incubated with tritium labelled androgens or estradiol to study the pattern of spermatozoa steroid metabolism. When equal concentrations of steroid substrates were used for incubation, monkey and human spermatozoa showed very similar pattern of steroid conversion. Spermatozoa from both species converted testosterone mainly to androstenedione, but reverse conversion of androstenedione to testosterone was negligible. Estradiol-17 beta was converted mainly to estrone. The close similarity between the spermatozoa of monkey and men in their steroid metabolic pattern indicates that the rhesus monkey could be an useful animal model to study the effect of drugs on the metabolic pattern of human spermatozoa

  7. Cell-poor septa separate representations of digits in the ventroposterior nucleus of the thalamus in monkeys and prosimian galagos.

    Science.gov (United States)

    Qi, Hui-Xin; Gharbawie, Omar A; Wong, Peiyan; Kaas, Jon H

    2011-03-01

    The architectonic features of the ventroposterior nucleus (VP) were visualized in coronal brain sections from two macaque monkeys, two owl monkeys, two squirrel monkeys, and three galagos that were processed for cytochrome oxidase, Nissl bodies, or the vesicular glutamate transporter 2 (vGluT2). The traditional ventroposterior medial (VPM) and ventroposterior lateral (VPL) subnuclei were easily identified, as well as the forelimb and hindlimb compartments of VPL, as they were separated by poorly staining, cell-poor septa. Septa also separated other cell groups within VPM and VPL, specifically in the medial compartment of VPL representing the hand (hand VPL). In one squirrel monkey and one galago we demonstrated that these five groups of cells represent digits 1-5 in a mediolateral sequence by injecting tracers into the cortical representation of single digits, defined by microelectrode recordings, and relating concentrations of labeled neurons to specific cell groups in hand VPL. The results establish the existence of septa that isolate the representation of the five digits in VPL of primates and demonstrate that the isolated cell groups represent digits 1-5 in a mediolateral sequence. The present results show that the septa are especially prominent in brain sections processed for vGluT2, which is expressed in the synaptic terminals of excitatory neurons in most nuclei of the brainstem and thalamus. As vGluT2 is expressed in the synaptic terminations from dorsal columns and trigeminal brainstem nuclei, the effectiveness of vGluT2 preparations in revealing septa in VP likely reflects a lack of synapses using glutamate in the septa. Copyright © 2010 Wiley-Liss, Inc.

  8. Exploring the extent and function of higher-order auditory cortex in rhesus monkeys.

    Science.gov (United States)

    Poremba, Amy; Mishkin, Mortimer

    2007-07-01

    Just as cortical visual processing continues far beyond the boundaries of early visual areas, so too does cortical auditory processing continue far beyond the limits of early auditory areas. In passively listening rhesus monkeys examined with metabolic mapping techniques, cortical areas reactive to auditory stimulation were found to include the entire length of the superior temporal gyrus (STG) as well as several other regions within the temporal, parietal, and frontal lobes. Comparison of these widespread activations with those from an analogous study in vision supports the notion that audition, like vision, is served by several cortical processing streams, each specialized for analyzing a different aspect of sensory input, such as stimulus quality, location, or motion. Exploration with different classes of acoustic stimuli demonstrated that most portions of STG show greater activation on the right than on the left regardless of stimulus class. However, there is a striking shift to left-hemisphere "dominance" during passive listening to species-specific vocalizations, though this reverse asymmetry is observed only in the region of temporal pole. The mechanism for this left temporal pole "dominance" appears to be suppression of the right temporal pole by the left hemisphere, as demonstrated by a comparison of the results in normal monkeys with those in split-brain monkeys.

  9. Parity modifies endocrine hormones in urine and problem-solving strategies of captive owl monkeys (Aotus spp.).

    Science.gov (United States)

    Bardi, Massimo; Eckles, Meredith; Kirk, Emily; Landis, Timothy; Evans, Sian; Lambert, Kelly G

    2014-12-01

    Parental behavior modifies neural, physiologic, and behavioral characteristics of both maternal and paternal mammals. These parenting-induced modifications extend to brain regions not typically associated with parental responses themselves but that enhance ancillary responses, such as foraging efficiency and predator avoidance. Here we hypothesized that male and female owl monkeys (Aotus spp.) with reproductive experience (RE) would demonstrate more adaptive ancillary behavioral and neuroendocrine responses than those of their nonRE counterparts. To assess cognitive skills and coping flexibility, we introduced a foraging strategy task, including a set of novel objects (coin holders) marked with different symbols representing different food rewards, to the animals. To assess endocrine responses, urine samples were assayed for cortisol and dehydroepiandrosterone (DHEA) levels and their ratios to determine physiologic measures of emotional regulation in RE and nonRE owl monkeys. Compared with nonRE monkeys, experienced parents had higher DHEA:cortisol ratios after exposure to habituation training and on the first day of testing in the foraging task. Both hormones play critical roles in the stress response and coping mechanisms, and a high DHEA:cortisol ratio usually indicates increased coping skills. In addition, RE monkeys exhibited more efficient foraging responses (by 4-fold) than did the nonRE mating pairs. We conclude that RE modifies relevant behavioral and hormonal responses of both maternal and paternal owl monkeys exposed to a challenging cognitive paradigm. Corroborating previous research demonstrating adaptive modifications in foraging efficiency and emotional responses in reproductively experienced rodents, the current results extend these findings to a monogamous primate species.

  10. Placental Transport of Zidovudine in the Rhesus Monkey

    OpenAIRE

    Ridgway III, Louis E.; King, Thomas S.; Henderson, George I.; Schenker, Steven; Schenken, Robert S.

    1993-01-01

    Objective: This study was undertaken to characterize the pharmacokinetics of zidovudine (ZDV) and ZDV-glucuronide (ZDVG) in the material and :fetal circulations of the rhesus monkey. Methods: Cannulas were placed in the maternal external jugular and the fetal internal jugular and carotid artery in 8 pregnant monkeys at .120–130 days gestation. ZDV (3.5 mg/kg) was administered to 5 monkeys and ZDVG (3.5 mg/kg) to 3 monkeys as single intravenous bolus infusions through the maternal catheter. Ma...

  11. Study on Control of Brain Temperature for Brain Hypothermia Treatment

    Science.gov (United States)

    Gaohua, Lu; Wakamatsu, Hidetoshi

    The brain hypothermia treatment is an attractive therapy for the neurologist because of its neuroprotection in hypoxic-ischemic encephalopathy patients. The present paper deals with the possibility of controlling the brain and other viscera in different temperatures from the viewpoint of system control. It is theoretically attempted to realize the special brain hypothermia treatment to cool only the head but to warm the body by using the simple apparatus such as the cooling cap, muffler and warming blanket. For this purpose, a biothermal system concerning the temperature difference between the brain and the other thoracico-abdominal viscus is synthesized from the biothermal model of hypothermic patient. The output controllability and the asymptotic stability of the system are examined on the basis of its structure. Then, the maximum temperature difference to be realized is shown dependent on the temperature range of the apparatus and also on the maximum gain determined from the coefficient matrices A, B and C of the biothermal system. Its theoretical analysis shows the realization of difference of about 2.5°C, if there is absolutely no constraint of the temperatures of the cooling cap, muffler and blanket. It is, however, physically unavailable. Those are shown by simulation example of the optimal brain temperature regulation using a standard adult database. It is thus concluded that the surface cooling and warming apparatus do no make it possible to realize the special brain hypothermia treatment, because the brain temperature cannot be cooled lower than those of other viscera in an appropriate temperature environment. This study shows that the ever-proposed good method of clinical treatment is in principle impossible in the actual brain hypothermia treatment.

  12. Effect of silhouetting and inversion on view invariance in the monkey inferotemporal cortex.

    Science.gov (United States)

    Ratan Murty, N Apurva; Arun, S P

    2017-07-01

    We effortlessly recognize objects across changes in viewpoint, but we know relatively little about the features that underlie viewpoint invariance in the brain. Here, we set out to characterize how viewpoint invariance in monkey inferior temporal (IT) neurons is influenced by two image manipulations-silhouetting and inversion. Reducing an object into its silhouette removes internal detail, so this would reveal how much viewpoint invariance depends on the external contours. Inverting an object retains but rearranges features, so this would reveal how much viewpoint invariance depends on the arrangement and orientation of features. Our main findings are 1 ) view invariance is weakened by silhouetting but not by inversion; 2 ) view invariance was stronger in neurons that generalized across silhouetting and inversion; 3 ) neuronal responses to natural objects matched early with that of silhouettes and only later to that of inverted objects, indicative of coarse-to-fine processing; and 4 ) the impact of silhouetting and inversion depended on object structure. Taken together, our results elucidate the underlying features and dynamics of view-invariant object representations in the brain. NEW & NOTEWORTHY We easily recognize objects across changes in viewpoint, but the underlying features are unknown. Here, we show that view invariance in the monkey inferotemporal cortex is driven mainly by external object contours and is not specialized for object orientation. We also find that the responses to natural objects match with that of their silhouettes early in the response, and with inverted versions later in the response-indicative of a coarse-to-fine processing sequence in the brain. Copyright © 2017 the American Physiological Society.

  13. Metabolic alkalosis during immobilization in monkeys (M. nemestrina)

    Science.gov (United States)

    Young, D. R.; Yeh, I.; Swenson, R. S.

    1983-01-01

    The systemic and renal acid-base response of monkeys during ten weeks of immobilization was studied. By three weeks of immobilization, arterial pH and bicarbonate concentrations were elevated (chronic metabolic alkalosis). Net urinary acid excretion increased in immobilized animals. Urinary bicarbonate excretion decreased during the first three weeks of immobilization, and then returned to control levels. Sustained increases in urinary ammonium excretion were seen throughout the time duration of immobilization. Neither potassium depletion nor hypokalemia was observed. Most parameters returned promptly to the normal range during the first week of recovery. Factors tentatively associated with changes in acid-base status of monkeys include contraction of extracellular fluid volume, retention of bicarbonate, increased acid excretion, and possible participation of extrarenal buffers.

  14. Canine Distemper Outbreak in Rhesus Monkeys, China

    Science.gov (United States)

    Qiu, Wei; Zheng, Ying; Zhang, Shoufeng; Fan, Quanshui; Liu, Hua; Zhang, Fuqiang; Wang, Wei; Liao, Guoyang

    2011-01-01

    Since 2006, canine distemper outbreaks have occurred in rhesus monkeys at a breeding farm in Guangxi, People’s Republic of China. Approximately 10,000 animals were infected (25%–60% disease incidence); 5%–30% of infected animals died. The epidemic was controlled by vaccination. Amino acid sequence analysis of the virus indicated a unique strain. PMID:21801646

  15. Dissociation of Active Working Memory and Passive Recognition in Rhesus Monkeys

    Science.gov (United States)

    Basile, Benjamin M.; Hampton, Robert R.

    2013-01-01

    Active cognitive control of working memory is central in most human memory models, but behavioral evidence for such control in nonhuman primates is absent and neurophysiological evidence, while suggestive, is indirect. We present behavioral evidence that monkey memory for familiar images is under active cognitive control. Concurrent cognitive…

  16. Autoshaping in Japanese Monkeys (Macaca Fuscata)

    OpenAIRE

    Itakura, Shoji; Fushimi, Takao; Asano, Toshio; Shoji, Itakura; Takao, Fushimi; Toshio, Asano

    1992-01-01

    Three Japanese monkeys were exposed to autoshaping and omission procedures. The Japanese momkeys seemed to be more sensitive to response-reinforcer contingency than to stimulus-reinforcer contingency. These results were compared with pigeons and squirrel monkeys in the previous reports.

  17. Chronic marijuana smoke exposure in the rhesus monkey. IV: Neurochemical effects and comparison to acute and chronic exposure to delta-9-tetrahydrocannabinol (THC) in rats.

    Science.gov (United States)

    Ali, S F; Newport, G D; Scallet, A C; Paule, M G; Bailey, J R; Slikker, W

    1991-11-01

    THC is the major psychoactive constituent of marijuana and is known to produce psychopharmacological effects in humans. These studies were designed to determine whether acute or chronic exposure to marijuana smoke or THC produces in vitro or in vivo neurochemical alterations in rat or monkey brain. For the in vitro study, THC was added (1-100 nM) to membranes prepared from different regions of the rat brain and muscarinic cholinergic (MCh) receptor binding was measured. For the acute in vivo study, rats were injected IP with vehicle, 1, 3, 10, or 30 mg THC/kg and sacrificed 2 h later. For the chronic study, rats were gavaged with vehicle or 10 or 20 mg THC/kg daily, 5 days/week for 90 days and sacrificed either 24 h or 2 months later. Rhesus monkeys were exposed to the smoke of a single 2.6% THC cigarette once a day, 2 or 7 days a week for 1 year. Approximately 7 months after the last exposure, animals were sacrificed by overdose with pentobarbital for neurochemical analyses. In vitro exposure to THC produced a dose-dependent inhibition of MCh receptor binding in several brain areas. This inhibition of MCh receptor binding, however, was also observed with two other nonpsychoactive derivatives of marijuana, cannabidiol and cannabinol. In the rat in vivo study, we found no significant changes in MCh or other neurotransmitter receptor binding in hippocampus, frontal cortex or caudate nucleus after acute or chronic exposure to THC. In the monkey brain, we found no alterations in the concentration of neurotransmitters in caudate nucleus, frontal cortex, hypothalamus or brain stem.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Autoshaping and automaintenance of a key-press response in squirrel monkeys.

    Science.gov (United States)

    Gamzu, E; Schwam, E

    1974-03-01

    Following exposure for a minimum of 500 to 600 trials, three of four naive squirrel monkeys eventually pressed a response key, illumination of which always preceded delivery of a food pellet. Three other naive monkeys did not press the key when the pellets were delivered randomly with respect to key illumination. Despite some similarities to autoshaping using pigeons, the data indicate many points of difference when squirrel monkeys are used as subjects. Although key-food pairings were shown to be important in the acquisition of the key-press response, they were ineffective in maintaining the response when either a negative response-reinforcer dependency was introduced, or when there was no scheduled response-reinforcer dependency (fixed trial). Not all demonstrations of autoshaping can be considered to be under the control of those processes that are primarily responsible for the phenomena obtained in pigeons.

  19. Monkeys Wait to Begin a Computer Task when Waiting Makes Their Responses More Effective

    Directory of Open Access Journals (Sweden)

    Theodore A. Evans

    2014-02-01

    Full Text Available Rhesus monkeys (Macaca mulatta and capuchin monkeys (Cebus apella performed a computerized inhibitory control task modeled after an “escalating interest task” from a recent human study (Young, Webb, & Jacobs, 2011. In the original study, which utilized a first-person shooter game, human participants learned to inhibit firing their simulated weapon long enough for the weapon‟s damage potential to grow in effectiveness (up to 10 seconds in duration. In the present study, monkeys earned food pellets for eliminating arrays of target objects using a digital eraser. We assessed whether monkeys could suppress trial-initiating joystick movements long enough for the eraser to grow in size and speed, thereby making their eventual responses more effective. Monkeys of both species learned to inhibit moving the eraser for as long as 10 seconds, and they allowed the eraser to grow larger for successively larger target arrays. This study demonstrates an interesting parallel in behavioral inhibition between human and nonhuman participants and provides a method for future comparative testing of human and nonhuman test groups.

  20. The 3D Printing of the Paralyzed Vocal Fold: Added Value in Injection Laryngoplasty.

    Science.gov (United States)

    Hamdan, Abdul-Latif; Haddad, Ghassan; Haydar, Ali; Hamade, Ramsey

    2017-08-18

    Three-dimensional (3D) printing has had numerous applications in various disciplines, especially otolaryngology. We report the first case of a high-fidelity 3D-printed model of the vocal cords of a patient with unilateral vocal cord paralysis in need of injection laryngoplasty. A case report was carried out. A tailored 3D-printed anatomically precise models for injection laryngoplasty has the potential to enhance preoperative planning, resident teaching, and patient education. A 3D printing model of the paralyzed vocal cord has an added value in the preoperative assessment of patients undergoing injection laryngoplasty. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  1. Lentivirus-mediated RNA interference of vascular endothelial growth factor in monkey eyes with iris neovascularization.

    Science.gov (United States)

    Yuan, Meng-Ke; Tao, Yong; Yu, Wen-Zhen; Kai, Wang; Jiang, Yan-Rong

    2010-08-25

    To explore the in vivo anti-angiogenesis effects resulting from lentivirus-mediated RNAi of vascular endothelial growth factor (VEGF) in monkeys with iris neovascularization (INV). Five specific recombinant lentiviral vectors for RNA interference, targeting Macaca mulatta VEGFA, were designed and the one with best knock down efficacy (LV-GFP-VEGFi1) in H1299 cells and RF/6A cells was selected by real-time PCR for in vivo use. A laser-induced retinal vein occlusion model was established in one eye of seven cynomolgus monkeys. In monkeys number 1, 3, and 5 (Group 1), the virus (1x10(8) particles) was intravitreally injected into the preretinal space of the animal's eye immediately after laser coagulation; and in monkeys number 2, 4, and 6 (Group 2), the virus (1x10(8) particles) was injected at 10 days after laser coagulation. In monkey number 7, a blank control injection was performed. In monkeys number 1 and 2, virus without RNAi sequence was used; in monkeys number 3 and 4, virus with nonspecific RNAi sequence was used; and in monkeys 5 and 6, LV-GFP-VEGFi1 was used. In monkey number 5, at 23 days after laser treatment, no obvious INV was observed, while fluorescein angiography of the iris revealed high fluorescence at the margin of pupil and point posterior synechiae. At 50 days after laser treatment, only a slight ectropion uvea was found. However, in the other eyes, obvious INV or hyphema was observed. The densities of new iridic vessels all significantly varied: between monkey number 5 and number 3 (36.01+/-4.49/mm(2) versus 48.68+/-9.30/mm(2), p=0.025), between monkey number 3 and monkey number 7 (48.68+/-9.30/mm(2) versus 74.38+/-9.23/mm(2), p=0.002), and between monkey number 5 and number 7 (36.01+/-4.49/mm(2) versus 74.38+/-9.23/mm(2), p<0.001). Lentivirus-mediated RNAi of VEGF may be a new strategy to treat iris neovascularization, while further studies are needed to investigate the long-term effect.

  2. The effects of chronic alcohol self-administration in nonhuman primate brain networks.

    Science.gov (United States)

    Telesford, Qawi K; Laurienti, Paul J; Davenport, April T; Friedman, David P; Kraft, Robert A; Daunais, James B

    2015-04-01

    Long-term alcohol abuse is associated with change in behavior, brain structure, and brain function. However, the nature of these changes is not well understood. In this study, we used network science to analyze a nonhuman primate model of ethanol self-administration to evaluate functional differences between animals with chronic alcohol use and animals with no exposure to alcohol. Of particular interest was how chronic alcohol exposure may affect the resting state network. Baseline resting state functional magnetic resonance imaging was acquired in a cohort of vervet monkeys. Animals underwent an induction period where they were exposed to an isocaloric maltose dextrin solution (control) or ethanol in escalating doses over three 30-day epochs. Following induction, animals were given ad libitum access to water and a maltose dextrin solution (control) or water and ethanol for 22 h/d over 12 months. Cross-sectional analyses examined region of interests in hubs and community structure across animals to determine differences between drinking and nondrinking animals after the 12-month free access period. Animals were classified as lighter (intake pattern during the 12-month ethanol free access period. Statistical analysis of hub connectivity showed significant differences in heavier drinkers for hubs in the precuneus, posterior parietal cortices, superior temporal gyrus, subgenual cingulate, and sensorimotor cortex. Heavier drinkers were also shown to have less consistent communities across the brain compared to lighter drinkers. The different level of consumption between the lighter and heavier drinking monkeys suggests that differences in connectivity may be intake dependent. Animals that consume alcohol show topological differences in brain network organization, particularly in animals that drink heavily. Differences in the resting state network were linked to areas that are associated with spatial association, working memory, and visuomotor processing. Copyright

  3. Homogeneous antibodies in lethally irradiated and autologous bone marrow reconstituted Rhesus monkeys

    International Nuclear Information System (INIS)

    Berg, P. Van Den; Radl, J.; Loewenberg, B.; Swart, A.C.W.

    1976-01-01

    Ten Rhesus monkeys were lethally irradiated and reconstituted with autologous bone marrow. During the restoration period, the animals were immunized with DNP-Rhesus albumin and IgA1lambda-10S human paraprotein. One or more transient homogenous immunoglobulin components appeared in sera of all experimental monkeys. In four animals, these homogeneous immunoglobulins were shown to be specific antibodies against DNP-Rhesus albumin. They gradually became as heterogeneous as those in control monkeys which were immunized but not irradiated and transplanted. The onset of the specific antibody response after immunization was slightly delayed in the experimental group. On determining the time necessary to reach normalization of the overall immunoglobulin levels and the normal heterogeneity of the immunoglobulin spectrum, it was found to be more than 1 year in most of the animals. (author)

  4. Avalanche analysis from multi-electrode ensemble recordings in cat, monkey and human cerebral cortex during wakefulness and sleep.

    Directory of Open Access Journals (Sweden)

    Nima eDehghani

    2012-08-01

    Full Text Available Self-organized critical states are found in many natural systems, from earthquakes to forest fires, they have also been observed in neural systems, particularly, in neuronal cultures. However, the presence of critical states in the awake brain remains controversial. Here, we compared avalanche analyses performed on different in vivo preparations during wakefulness, slow-wave sleep and REM sleep, using high-density electrode arrays in cat motor cortex (96 electrodes, monkey motor cortex and premotor cortex and human temporal cortex (96 electrodes in epileptic patients. In neuronal avalanches defined from units (up to 160 single units, the size of avalanches never clearly scaled as power-law, but rather scaled exponentially or displayed intermediate scaling. We also analyzed the dynamics of local field potentials (LFPs and in particular LFP negative peaks (nLFPs among the different electrodes (up to 96 sites in temporal cortex or up to 128 sites in adjacent motor and pre-motor cortices. In this case, the avalanches defined from nLFPs displayed power-law scaling in double logarithmic representations, as reported previously in monkey. However, avalanche defined as positive LFP (pLFP peaks, which are less directly related to neuronal firing, also displayed apparent power-law scaling. Closer examination of this scaling using the more reliable cumulative distribution function (CDF and other rigorous statistical measures, did not confirm power-law scaling. The same pattern was seen for cats, monkey and human, as well as for different brain states of wakefulness and sleep. We also tested other alternative distributions. Multiple exponential fitting yielded optimal fits of the avalanche dynamics with bi-exponential distributions. Collectively, these results show no clear evidence for power-law scaling or self-organized critical states in the awake and sleeping brain of mammals, from cat to man.

  5. Comparative response of dogs and monkeys to sublethal acute and continuous low dose-rate gamma-ray exposure

    International Nuclear Information System (INIS)

    Spalding, J.F.; Holland, L.M.; Johnson, O.S.; LaBauve, P.M.; London, J.E.; Prine, J.R.; Vigil, E.A.

    1977-02-01

    Monkeys (Macaca mulatta) and dogs (beagle) were given thirteen 100-rad gamma-ray doses at 28-day intervals. The comparative response (injury and recovery) of the hematopoietic system of the two species was observed at 7-day intervals during the exposure regime. At 84 days after the thirteenth gamma-ray dose, the 1300-rad conditioned and control dogs and monkeys were challenged continuously with 35 R/day until death to determine the amount of radiation-induced injury remaining in conditioned animals as a reduction in mean survival time. Dogs (50 percent) and monkeys (8 percent) died from injury incurred during the conditioning exposures. Thus, the comparative response of dogs and monkeys to dose protraction by acute dose fractionation was similar to what might be expected from a single acute dose. Mean survival times for nonconditioned dogs and monkeys during continuous exposure at 35 R/day were the same (approximately 1400 h). Thus, hematopoietic response of the two species by this method of dose protraction was not significantly different. Mean survival times of conditioned dogs and monkeys during the continuous 35 R/day gamma-ray challenge exposure were greater than for their control counterparts. Thus, the long-term radiation-induced injury was not measurable by this method. Conditioning doses of more than four times the acute LD 50 - 30 in dogs and approximately two times that of monkeys served only to increase both mean survival time and variance in a gamma-ray stress environment with a dose rate of 35 R/day

  6. A longitudinal analysis of regional brain volumes in macaques exposed to X-irradiation in early gestation.

    Directory of Open Access Journals (Sweden)

    Kristina Aldridge

    Full Text Available Early gestation represents a period of vulnerability to environmental insult that has been associated with adult psychiatric disease. However, little is known about how prenatal perturbation translates into adult brain dysfunction. Here, we use a longitudinal study design to examine the effects of disruption of early gestational neurogenesis on brain volume in the non-human primate.Five Rhesus macaques were exposed to x-irradiation in early gestation (E30-E41, and four control monkeys were sham-irradiated at comparable ages. Whole brain magnetic resonance imaging was performed at 6 months, 12 months, and 3 and 5 years of age. Volumes of whole cerebrum, cortical gray matter, caudate, putamen, and thalamus were estimated using semi-automated segmentation methods and high dimensional brain mapping. Volume reductions spanning all ages were observed in irradiated monkeys in the putamen (15-24%, p = 0.01 and in cortical gray matter (6-15%, p = 0.01. Upon covarying for whole cerebral volume, group differences were reduced to trend levels (putamen: p = 0.07; cortical gray matter: p = 0.08. No group-by-age effects were significant.Due to the small number of observations, the conclusions drawn from this study must be viewed as tentative. Early gestational irradiation may result in non-uniform reduction of gray matter, mainly affecting the putamen and cerebral cortex. This may be relevant to understanding how early prenatal environmental insult could lead to brain morphological differences in neurodevelopmental diseases.

  7. Using an Artificial Neural Bypass to Restore Cortical Control of Rhythmic Movements in a Human with Quadriplegia

    Science.gov (United States)

    Sharma, Gaurav; Friedenberg, David A.; Annetta, Nicholas; Glenn, Bradley; Bockbrader, Marcie; Majstorovic, Connor; Domas, Stephanie; Mysiw, W. Jerry; Rezai, Ali; Bouton, Chad

    2016-09-01

    Neuroprosthetic technology has been used to restore cortical control of discrete (non-rhythmic) hand movements in a paralyzed person. However, cortical control of rhythmic movements which originate in the brain but are coordinated by Central Pattern Generator (CPG) neural networks in the spinal cord has not been demonstrated previously. Here we show a demonstration of an artificial neural bypass technology that decodes cortical activity and emulates spinal cord CPG function allowing volitional rhythmic hand movement. The technology uses a combination of signals recorded from the brain, machine-learning algorithms to decode the signals, a numerical model of CPG network, and a neuromuscular electrical stimulation system to evoke rhythmic movements. Using the neural bypass, a quadriplegic participant was able to initiate, sustain, and switch between rhythmic and discrete finger movements, using his thoughts alone. These results have implications in advancing neuroprosthetic technology to restore complex movements in people living with paralysis.

  8. [Hybrids of human and monkey adenoviruses (adeno-adeno hybrids) that can reproduce in monkey cells: biological and molecular genetic peculiarities].

    Science.gov (United States)

    Grinenko, N F; Savitskaia, N V; Pashvykina, G V; Al'tshteĭn, A D

    2003-06-01

    A highly oncogenic monkey adenovirus SA7(C8) facilitates the reproduction of human adenovirus type 2 (Ad2) in monkey cells. Upon mixed infection of monkey cells with both viruses, these viruses recombine producing defective adeno-adeno hybrids Ad2C8 serologically identical to Ad2 and capable of assisting Ad2 to reproduce in monkey cells. Ad2C8 and Ad2 form an intercomplementary pair inseparable in monkey cells. Unlike oncogenic SA7(C8), Ad2C8 is a nononcogenic virus for hamsters but is able to induce tumor antigens of this virus (T and TSTA). Molecular genetic analysis of 68 clones of adeno-adeno hybrids revealed that the left part of their genome consists of Ad2 DNA, and the right part contains no less than 40% of the viral SA7(C8) genome where E2A, E3, and E4 genes are located. Apparently, the products of these genes contribute to the composition of adenoviral tumor antigens, while the E4 gene is involved in complementation of monkey and human adenoviruses and makes a contribution to host range determination of these viruses.

  9. Cholinergic and serotonergic modulation of visual information processing in monkey V1.

    Science.gov (United States)

    Shimegi, Satoshi; Kimura, Akihiro; Sato, Akinori; Aoyama, Chisa; Mizuyama, Ryo; Tsunoda, Keisuke; Ueda, Fuyuki; Araki, Sera; Goya, Ryoma; Sato, Hiromichi

    2016-09-01

    The brain dynamically changes its input-output relationship depending on the behavioral state and context in order to optimize information processing. At the molecular level, cholinergic/monoaminergic transmitters have been extensively studied as key players for the state/context-dependent modulation of brain function. In this paper, we review how cortical visual information processing in the primary visual cortex (V1) of macaque monkey, which has a highly differentiated laminar structure, is optimized by serotonergic and cholinergic systems by examining anatomical and in vivo electrophysiological aspects to highlight their similarities and distinctions. We show that these two systems have a similar layer bias for axonal fiber innervation and receptor distribution. The common target sites are the geniculorecipient layers and geniculocortical fibers, where the appropriate gain control is established through a geniculocortical signal transformation. Both systems exert activity-dependent response gain control across layers, but in a manner consistent with the receptor subtype. The serotonergic receptors 5-HT1B and 5HT2A modulate the contrast-response curve in a manner consistent with bi-directional response gain control, where the sign (facilitation/suppression) is switched according to the firing rate and is complementary to the other. On the other hand, cholinergic nicotinic/muscarinic receptors exert mono-directional response gain control without a sign reversal. Nicotinic receptors increase the response magnitude in a multiplicative manner, while muscarinic receptors exert both suppressive and facilitative effects. We discuss the implications of the two neuromodulator systems in hierarchical visual signal processing in V1 on the basis of the developed laminar structure. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Characterisation of the appearance of radioactive metabolites in monkey and human plasma from the 5-HT1A receptor radioligand, [carbonyl-11C]WAY-100635 - explanation of high signal contrast in PET and an aid to biomathematical modelling

    International Nuclear Information System (INIS)

    Osman, Safiye; Lundkvist, Camilla; Pike, Victor W.; Halldin, Christer; McCarron, Julie A.; Swahn, Carl-Gunnar; Farde, Lars; Ginovart, Nathalie; Luthra, Sajinder K.; Gunn, Roger N.; Bench, Christopher J.; Sargent, Peter A.; Grasby, Paul M.

    1998-01-01

    N-(2-(4-(2-Methoxy-phenyl)-1-piperazin-1-yl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide (WAY-100635), labelled in its amido carbonyl group with 11 C (t 1/2 = 20.4 min), is a promising radioligand for the study of brain 5-HT 1A receptors with positron emission tomography (PET). Thus, in PET experiments in six cynomolgus monkeys and seven healthy male volunteers, [carbonyl- 11 C]WAY-100635 was taken up avidly by brain. Radioactivity was retained in regions rich in 5-HT 1A receptors, such as occipital cortex, temporal cortex and raphe nuclei, but cleared rapidly from cerebellum, a region almost devoid of 5-HT 1A receptors. [Carbonyl- 11 C]WAY-100635 provides about 3- and 10-fold higher signal contrast (receptor-specific to nonspecific binding) than [O-methyl- 11 C]WAY-100635 in receptor-rich areas of monkey and human brain, respectively. To elucidate the effect of label position on radioligand behaviour and to aid in the future biomathematical interpretation of the kinetics of regional cerebral radioactivity uptake in terms of receptor-binding parameters, HPLC was used to measure [carbonyl- 11 C]WAY-100635 and its radioactive metabolites in plasma at various times after intravenous injection. Radioactivity cleared rapidly from monkey and human plasma. Parent radioligand represented 19% of the radioactivity in monkey plasma at 47 min and 8% of the radioactivity in human plasma at 40 min. [Carbonyl- 11 C]desmethyl-WAY-100635 was below detectable limits in monkey plasma and at most a very minor radioactive metabolite in human plasma. [ 11 C]Cyclohexanecarboxylic acid was identified as a significant radioactive metabolite. In human plasma this maximally represented 21% of the radioactivity at 10 min after radioligand injection. All other major radioactive metabolites in monkey and human plasma were even more polar. No-carrier-added [carbonyl- 11 C]cyclohexanecarboxylic acid was prepared in the laboratory and after intravenous administration into cynomolgus monkey was

  11. Monkey Bites among US Military Members, Afghanistan, 2011

    Science.gov (United States)

    Baker, Katheryn A.

    2012-01-01

    Bites from Macaca mulatta monkeys, native to Afghanistan, can cause serious infections. To determine risk for US military members in Afghanistan, we reviewed records for September–December 2011. Among 126 animal bites and exposures, 10 were monkey bites. Command emphasis is vital for preventing monkey bites; provider training and bite reporting promote postexposure treatment. PMID:23017939

  12. Metabolic changes in the visual cortex of binocular blindness macaque monkeys: a proton magnetic resonance spectroscopy study.

    Directory of Open Access Journals (Sweden)

    Lingjie Wu

    Full Text Available PURPOSE: To evaluate proton magnetic resonance spectroscopy ((1H-MRS in a study of cross-modal plasticity in the visual cortex of binocular blindness macaque monkeys. MATERIALS AND METHODS: Four healthy neonatal macaque monkeys were randomly divided into 2 groups, with 2 in each group. Optic nerve transection was performed in both monkeys in the experimental group (group B to obtain binocular blindness. Two healthy macaque monkeys served as a control group (group A. After sixteen months post-procedure, (1H-MRS was performed in the visual cortex of all monkeys. We compared the peak areas of NAA, Cr, Cho, Glx and Ins and the ratios of NAA/Cr, Cho/Cr, Glx/Cr and Ins/Cr of each monkey in group B with group A. RESULTS: The peak area of NAA and the NAA/Cr ratio in the visual cortex of monkey 4 in group B were found to be dramatically decreased, the peak area of NAA slightly decreased and the NAA/Cr ratio clearly decreased in visual cortex of monkey 3 in group B than those in group A. The peak area of Ins and the Ins/Cr ratio in the visual cortex of monkey 4 in group B slightly increased. The peak area of Cho and the Cho/Cr ratio in the visual cortex of all monkeys in group B dramatically increased compared with group A. The peak area of Glx in the visual cortex of all monkeys in group B slightly increased compared with group A. CONCLUSIONS: (1H-MRS could detect biochemical and metabolic changes in the visual cortex and therefore this technique can be used to provide valuable information for investigating the mechanisms of cross-modal plasticity of binocular blindness in a macaque monkey model.

  13. Brain temperature profiles during epidural cooling with the ChillerPad in a monkey model of traumatic brain injury.

    Science.gov (United States)

    King, Christopher; Robinson, Timothy; Dixon, C Edward; Rao, Gutti R; Larnard, Donald; Nemoto, C Edwin M

    2010-10-01

    Therapeutic hypothermia remains a promising treatment for patients with severe traumatic brain injury (TBI). Multiple animal studies have suggested that hypothermia is neuroprotective after TBI, but clinical trials have been inconclusive. Systemic hypothermia, the method used in almost all major clinical trials, is limited by the time to target temperature, the depth of hypothermia, and complications, problems that may be solved by selective brain cooling. We evaluated the effects on brain temperature of a cooling device called the ChillerPad,™ which is applied to the dura in a non-human primate TBI model using controlled cortical impact (CCI). The cortical surface was rapidly cooled to approximately 15°C and maintained at that level for 24 h, followed by rewarming over about 10 h. Brain temperatures fell to 34-35°C at a depth of 15 mm at the cortical gray/white matter interface, and to 28-32°C at 10 mm deep. Intracranial pressure was mildly elevated (8-12 mm Hg) after cooling and rewarming, likely due to TBI. Other physiological variables were unchanged. Cooling was rapidly diminished at points distant from the cooling pad. The ChillerPad may be useful for highly localized cooling of the brain in circumstances in which a craniotomy is clinically indicated. However, because of the delay required by the craniotomy, other methods that are more readily available for inducing hypothermia may be used as a bridge between the time of injury to placement of the ChillerPad.

  14. New control strategies for neuroprosthetic systems

    NARCIS (Netherlands)

    Crago, Patrick E.; Veltink, Petrus H.; Lan, Ning; Abbas, James J.; Kantor, Carole

    1996-01-01

    The availability of techniques to artificially excite paralyzed muscles opens enormous potential for restoring both upper and lower extremity movements with neuroprostheses. Neuroprostheses must stimulate muscle, and control and regulate the artificial movements produced. Control methods to

  15. Loss of metabolites from monkey striatum during PET with FDOPA

    DEFF Research Database (Denmark)

    Cumming, P; Munk, O L; Doudet, D

    2001-01-01

    diffusion of [(18)F]fluorodopamine metabolites from brain. Consequently, time-radioactivity recordings of striatum are progressively influenced by metabolite loss. In linear analyses, the net blood-brain clearance of FDOPA (K(D)(i), ml g(-1) min(-1)) can be corrected for this loss by the elimination rate...... constant k(Lin)(cl) (min(-1)). Similarly, the DOPA decarboxylation rate constant (k(D)(3), min(-1)) calculated by compartmental analysis can also be corrected for metabolite loss by the elimination rate constant k(DA)(9) (min(-1)). To compare the two methods, we calculated the two elimination rate...... of the estimate was substantially improved upon correction for metabolite loss. The rate constants for metabolite loss were higher in MPTP-lesioned monkey striatum than in normal striatum. The high correlation between individual estimates of k(Lin)(cl) and k(DA)(9) suggests that both rate constants reveal loss...

  16. The Monkey game: A computerized verbal working memory task for self-reliant administration in primary school children.

    Science.gov (United States)

    Van de Weijer-Bergsma, Eva; Kroesbergen, Evelyn H; Jolani, Shahab; Van Luit, Johannes E H

    2016-06-01

    In two studies, the psychometric properties of an online self-reliant verbal working memory task (the Monkey game) for primary school children (6-12 years of age) were examined. In Study 1, children (n = 5,203) from 31 primary schools participated. The participants completed computerized verbal and visual-spatial working memory tasks (i.e., the Monkey game and the Lion game) and a paper-and-pencil version of Raven's Standard Progressive Matrices. Reading comprehension and math achievement test scores were obtained from the schools. First, the internal consistency of the Monkey game was examined. Second, multilevel modeling was used to examine the effects of classroom membership. Multilevel multivariate regression analysis was used to examine the Monkey game's concurrent relationship with the Lion game and its predictive relationships with reading comprehension and math achievement. Also, age-related differences in performance were examined. In Study 2, the concurrent relationships between the Monkey game and two tester-led computerized working memory tasks were further examined (n = 140). Also, the 1- and 2-year stability of the Monkey game was investigated. The Monkey game showed excellent internal consistency, good concurrent relationships with the other working memory measures, and significant age differences in performance. Performance on the Monkey game was also predictive of subsequent reading comprehension and mathematics performance, even after controlling for individual differences in intelligence. Performance on the Monkey game was influenced by classroom membership. The Monkey game is a reliable and suitable instrument for the online computerized and self-reliant assessment of verbal working memory in primary school children.

  17. Transplantation of adult monkey neural stem cells into a contusion spinal cord injury model in rhesus macaque monkeys

    DEFF Research Database (Denmark)

    Nemati, Shiva Nemati; Jabbari, Reza; Hajinasrollah, Mostafa

    2014-01-01

    , therefore, to explore the efficacy of adult monkey NSC (mNSC) in a primate SCI model. MATERIALS AND METHODS: In this experimental study, isolated mNSCs were analyzed by flow cytometry, immunocytochemistry, and RT-PCR. Next, BrdU-labeled cells were transplanted into a SCI model. The SCI animal model...... on Tarlov's scale and our established behavioral tests for monkeys. CONCLUSION: Our findings have indicated that mNSCs can facilitate recovery in contusion SCI models in rhesus macaque monkeys. Additional studies are necessary to determine the im- provement mechanisms after cell transplantation....

  18. Protective effect and the therapeutic index of indralin in juvenile rhesus monkeys

    International Nuclear Information System (INIS)

    Vasin, Mikhail V.; Antipov, Vsevolod V.; Ushakov, Igor B.; Semenov, Leonid F.; Lapin, Boris A.; Suvorov, Nikolai N.; Ilyin, Leonid A.

    2014-01-01

    The radioprotective effect of indralin in rhesus monkeys was examined over 60 d following gamma irradiation. Male and female rhesus macaques (Macaca mulatta) 2-3-years-old and weighing 2.1-3.5 kg were used. Animals were exposed to total-body gamma irradiation from 60 Co at a dose of 6.8 Gy (lethal dose, 100% lethality over 30 days). Indralin (40-120 mg kg -1 ) was administered intramuscularly 5 min prior to radiation exposure. Indralin taken at a dose of 120 mg kg -1 protected five out of six monkeys (compared with the radiation control group, in which all 10 animals died). The average effective dose of indralin in the monkeys exposed to gamma irradiation for 30 min was equal to 77.3 (63.3-94.3) mg kg -1 , and the maximum tolerated dose of indralin administered to monkeys was 800 mg kg -1 . Indralin reduced radiation-induced injuries in macaques, thus resulting in a less severe course of acute radiation syndrome. Delayed and less pronounced manifestation of the haemorrhagic syndrome of the disease, and milder forms of both leukopenia and anaemia were also noted. The therapeutic index for indralin, expressed as the ratio of the maximum tolerated dose to the average effective dose, was equal to 10. Therefore, indralin has a significant radioprotective effect against radiation and has a high therapeutic index in rhesus monkeys. (author)

  19. Activity-dependent regulation of MHC class I expression in the developing primary visual cortex of the common marmoset monkey

    Directory of Open Access Journals (Sweden)

    Schlumbohm Christina

    2011-01-01

    Full Text Available Abstract Background Several recent studies have highlighted the important role of immunity-related molecules in synaptic plasticity processes in the developing and adult mammalian brains. It has been suggested that neuronal MHCI (major histocompatibility complex class I genes play a role in the refinement and pruning of synapses in the developing visual system. As a fast evolutionary rate may generate distinct properties of molecules in different mammalian species, we studied the expression of MHCI molecules in a nonhuman primate, the common marmoset monkey (Callithrix jacchus. Methods and results Analysis of expression levels of MHCI molecules in the developing visual cortex of the common marmoset monkeys revealed a distinct spatio-temporal pattern. High levels of expression were detected very early in postnatal development, at a stage when synaptogenesis takes place and ocular dominance columns are formed. To determine whether the expression of MHCI molecules is regulated by retinal activity, animals were subjected to monocular enucleation. Levels of MHCI heavy chain subunit transcripts in the visual cortex were found to be elevated in response to monocular enucleation. Furthermore, MHCI heavy chain immunoreactivity revealed a banded pattern in layer IV of the visual cortex in enucleated animals, which was not observed in control animals. This pattern of immunoreactivity indicated that higher expression levels were associated with retinal activity coming from the intact eye. Conclusions These data demonstrate that, in the nonhuman primate brain, expression of MHCI molecules is regulated by neuronal activity. Moreover, this study extends previous findings by suggesting a role for neuronal MHCI molecules during synaptogenesis in the visual cortex.

  20. Audio-vocal interaction in single neurons of the monkey ventrolateral prefrontal cortex.

    Science.gov (United States)

    Hage, Steffen R; Nieder, Andreas

    2015-05-06

    Complex audio-vocal integration systems depend on a strong interconnection between the auditory and the vocal motor system. To gain cognitive control over audio-vocal interaction during vocal motor control, the PFC needs to be involved. Neurons in the ventrolateral PFC (VLPFC) have been shown to separately encode the sensory perceptions and motor production of vocalizations. It is unknown, however, whether single neurons in the PFC reflect audio-vocal interactions. We therefore recorded single-unit activity in the VLPFC of rhesus monkeys (Macaca mulatta) while they produced vocalizations on command or passively listened to monkey calls. We found that 12% of randomly selected neurons in VLPFC modulated their discharge rate in response to acoustic stimulation with species-specific calls. Almost three-fourths of these auditory neurons showed an additional modulation of their discharge rates either before and/or during the monkeys' motor production of vocalization. Based on these audio-vocal interactions, the VLPFC might be well positioned to combine higher order auditory processing with cognitive control of the vocal motor output. Such audio-vocal integration processes in the VLPFC might constitute a precursor for the evolution of complex learned audio-vocal integration systems, ultimately giving rise to human speech. Copyright © 2015 the authors 0270-6474/15/357030-11$15.00/0.

  1. Spontaneous expression of mirror self-recognition in monkeys after learning precise visual-proprioceptive association for mirror images.

    Science.gov (United States)

    Chang, Liangtang; Zhang, Shikun; Poo, Mu-Ming; Gong, Neng

    2017-03-21

    Mirror self-recognition (MSR) is generally considered to be an intrinsic cognitive ability found only in humans and a few species of great apes. Rhesus monkeys do not spontaneously show MSR, but they have the ability to use a mirror as an instrument to find hidden objects. The mechanism underlying the transition from simple mirror use to MSR remains unclear. Here we show that rhesus monkeys could show MSR after learning precise visual-proprioceptive association for mirror images. We trained head-fixed monkeys on a chair in front of a mirror to touch with spatiotemporal precision a laser pointer light spot on an adjacent board that could only be seen in the mirror. After several weeks of training, when the same laser pointer light was projected to the monkey's face, a location not used in training, all three trained monkeys successfully touched the face area marked by the light spot in front of a mirror. All trained monkeys passed the standard face mark test for MSR both on the monkey chair and in their home cage. Importantly, distinct from untrained control monkeys, the trained monkeys showed typical mirror-induced self-directed behaviors in their home cage, such as using the mirror to explore normally unseen body parts. Thus, bodily self-consciousness may be a cognitive ability present in many more species than previously thought, and acquisition of precise visual-proprioceptive association for the images in the mirror is critical for revealing the MSR ability of the animal.

  2. On Loss Aversion in Capuchin Monkeys

    Science.gov (United States)

    Silberberg, Alan; Roma, Peter G.; Huntsberry, Mary E.; Warren-Boulton, Frederick R.; Sakagami, Takayuki; Ruggiero, Angela M.; Suomi, Stephen J.

    2008-01-01

    Chen, Lakshminarayanan, and Santos (2006) claim to show in three choice experiments that monkeys react rationally to price and wealth shocks, but, when faced with gambles, display hallmark, human-like biases that include loss aversion. We present three experiments with monkeys and humans consistent with a reinterpretation of their data that…

  3. Administration of high doses of copper to capuchin monkeys does not cause liver damage but induces transcriptional activation of hepatic proliferative responses.

    Science.gov (United States)

    Araya, Magdalena; Núñez, Héctor; Pavez, Leonardo; Arredondo, Miguel; Méndez, Marco; Cisternas, Felipe; Pizarro, Fernando; Sierralta, Walter; Uauy, Ricardo; González, Mauricio

    2012-02-01

    Liver cells respond to copper loading upregulating protective mechanisms. However, to date, except for liver content, there are no good indicators that identify individuals with excess liver copper. We hypothesized that administering high doses of copper to young (5.5 mg Cu · kg⁻¹ . d⁻¹) and adult (7.5 mg Cu · kg⁻¹ . d⁻¹) capuchin monkeys would induce detectable liver damage. Study groups included adult monkeys (2 females, 2 males) 3-3.5 y old at enrollment treated with copper for 36 mo (ACu); age-matched controls (1 female, 3 males) that did not receive additional copper (AC); young monkeys (2 female, 2 males) treated from birth with copper for 36 mo (YCu); and young age-matched controls (2 female, 2 males) that did not receive additional copper (YC). We periodically assessed clinical, blood biochemical, and liver histological indicators and at 36 mo the hepatic mRNA abundance of MT2a, APP, DMT1, CTR1, HGF, TGFβ, and NFκΒ only in adult monkeys. After 36 mo, the liver copper concentration was 4-5 times greater in treated monkeys relative to controls. All monkeys remained healthy with normal routine serum biochemical indices and there was no evidence of liver tissue damage. Relative mRNA abundance of HGF, TGFβ and NFκB was significantly greater in ACu than in AC monkeys. In conclusion, capuchin monkeys exposed to copper at doses up to 50 times the current upper level enhanced expression of genes related to inflammation and injury without clinical, blood biochemical, or histological evidence of liver damage.

  4. Radioimmunoassay of parathyroid hormone (parathyrin) in monkey and man

    International Nuclear Information System (INIS)

    Hargis, G.K.; Williams, G.A.; Reynolds, W.A.; Kawahara, W.; Jackson, B.; Bowser, E.N.; Pitkin, R.M.

    1977-01-01

    A radioimmunoassay for rhesus monkey and human innumoreactive parathyrin was developed in which a selected anti-bovine parathyrin antiserum, radioiodinated purified bovine parathyrin tracer, and human parathyroid tissue-culture media standards were used. The resulting data indicate that the method is sensitive, specific, accurate and reproducible; it is valid for both the rhesus monkey and the human; the serum immunoreactive parathyrin concentration of the monkey is essentially the same as that in man; monkey immunoreactive parathyrin responds to changes in serum calcium concentration similarly to that in man; and the rhesus monkey is therefore a suitable species in which to study parathyroid physiology, from which conclusions can be applied to the human

  5. Control channels in the brain and their influence on brain executive functions

    Science.gov (United States)

    Meng, Qinglei; Choa, Fow-Sen; Hong, Elliot; Wang, Zhiguang; Islam, Mohammad

    2014-05-01

    In a computer network there are distinct data channels and control channels where massive amount of visual information are transported through data channels but the information streams are routed and controlled by intelligent algorithm through "control channels". Recent studies on cognition and consciousness have shown that the brain control channels are closely related to the brainwave beta (14-40 Hz) and alpha (7-13 Hz) oscillations. The high-beta wave is used by brain to synchronize local neural activities and the alpha oscillation is for desynchronization. When two sensory inputs are simultaneously presented to a person, the high-beta is used to select one of the inputs and the alpha is used to deselect the other so that only one input will get the attention. In this work we demonstrated that we can scan a person's brain using binaural beats technique and identify the individual's preferred control channels. The identified control channels can then be used to influence the subject's brain executive functions. In the experiment, an EEG measurement system was used to record and identify a subject's control channels. After these channels were identified, the subject was asked to do Stroop tests. Binaural beats was again used to produce these control-channel frequencies on the subject's brain when we recorded the completion time of each test. We found that the high-beta signal indeed speeded up the subject's executive function performance and reduced the time to complete incongruent tests, while the alpha signal didn't seem to be able to slow down the executive function performance.

  6. On the nature of directed behavior to drug-associated light cues in rhesus monkeys (Macaca mulatta).

    Science.gov (United States)

    Reilly, Mark P; Berndt, Sonja I; Woods, James H

    2016-11-01

    The present study investigated the role of drug-paired stimuli in controlling the behavior of rhesus monkeys. Systematic observations were made with nine monkeys who had a history of drug self-administration; they had been lever pressing to produce intravenous infusions of various drugs. These observations revealed that the stimulus light co-occurring with drug infusion produced robust and cue-directed behavior such as orienting, touching and biting. Experiment 1 showed that this light-directed behavior would occur in naïve monkeys exposed to a Pavlovian pairing procedure. Four monkeys were given response-independent injections of cocaine. In two monkeys, a red light preceded cocaine injections by 5 s, and a green light co-occurred with the 5-s cocaine injections. In the other two monkeys, the light presentations and cocaine injections occurred independently. Light-directed behavior occurred in all four monkeys within the first couple of trials and at high levels but decreased across sessions. The cocaine-paired stimulus maintained behavior longer and at higher levels than the uncorrelated stimuli. Furthermore, light-directed behavior was not maintained when cocaine was replaced with saline. Light-directed behavior did not occur in the absence of the lights. When these monkeys were subsequently trained to lever press for cocaine, light-directed behavior increased to levels higher than previously observed. Behavior directed towards drug-paired stimuli is robust, reliable and multiply determined; the mechanisms underlying this activity likely include Pavlovian conditioning, stimulus novelty, habituation and operant conditioning.

  7. Spider monkey, Muriqui and Woolly monkey relationships revisited.

    Science.gov (United States)

    de Lima, Margarida Maria Celeira; Sampaio, Iracilda; Vieira, Ricardo dos Santos; Schneider, Horacio

    2007-01-01

    The taxonomic relationships among the four genera of the Atelidae family, Alouatta (Howler), Ateles (Spider), Lagothrix (Woolly) and Brachyteles (Muriqui), have been the subject of great debate. In general, almost all authors agree with the assignment of Howler monkeys as the basal genus, either in its own tribe Alouattini or in the subfamily Alouattinae, but they disagree on the associations among the other members of the family. Muriquis have been grouped with Spider monkeys based on the fact that they share various behavioral and morphological characteristics. Cladistic analyses using morphological, biochemical, karyotype and behavioral characteristics depicted a phylogenetic tree that places Howler as the basal genus and the remaining genera in an unresolved politomy. More recent studies using molecular data have suggested that Muriqui and Woolly monkeys are sister groups. However, a recent study based on nuclear and mtDNA argued that politomy is what best represents the relationships among Spider, Woolly and Muriqui. To contribute to this debate we have added new data from two nuclear genes, Transferrin and von Willebrand Factor, and using an alignment of 17,997 bp we demonstrate that a total analysis strongly supports the Muriqui-Woolly clade. A gene-to-gene approach showed that four of the eight nuclear genes provide support for the Muriqui-Woolly clade, two strongly and two moderately, while none of the eight genes provide support for any alternative arrangement. The mitochondrial genes were not able to resolve the politomy. A possible reason for the difficulty in resolving atelid relationships may be the short period of time separating each cladogenetic event in the evolutionary process that shaped this family.

  8. Accumulation, Biotransformation, Histopathology and Paralysis in the Pacific Calico Scallop Argopecten ventricosus by the Paralyzing Toxins of the Dinoflagellate Gymnodinium catenatum

    OpenAIRE

    Escobedo-Lozano, Amada Y.; Estrada, Norma; Ascencio, Felipe; Contreras, Gerardo; Alonso-Rodriguez, Rosalba

    2012-01-01

    The dinoflagellate Gymnodinium catenatum produces paralyzing shellfish poisons that are consumed and accumulated by bivalves. We performed short-term feeding experiments to examine ingestion, accumulation, biotransformation, histopathology, and paralysis in the juvenile Pacific calico scallop Argopecten ventricosus that consume this dinoflagellate. Depletion of algal cells was measured in closed systems. Histopathological preparations were microscopic...

  9. Differential arousal regulation by prokineticin 2 signaling in the nocturnal mouse and the diurnal monkey.

    Science.gov (United States)

    Zhou, Qun-Yong; Burton, Katherine J; Neal, Matthew L; Qiao, Yu; Kanthasamy, Anumantha G; Sun, Yanjun; Xu, Xiangmin; Ma, Yuanye; Li, Xiaohan

    2016-08-18

    The temporal organization of activity/rest or sleep/wake rhythms for mammals is regulated by the interaction of light/dark cycle and circadian clocks. The neural and molecular mechanisms that confine the active phase to either day or night period for the diurnal and the nocturnal mammals are unclear. Here we report that prokineticin 2, previously shown as a circadian clock output molecule, is expressed in the intrinsically photosensitive retinal ganglion cells, and the expression of prokineticin 2 in the intrinsically photosensitive retinal ganglion cells is oscillatory in a clock-dependent manner. We further show that the prokineticin 2 signaling is required for the activity and arousal suppression by light in the mouse. Between the nocturnal mouse and the diurnal monkey, a signaling receptor for prokineticin 2 is differentially expressed in the retinorecipient suprachiasmatic nucleus and the superior colliculus, brain projection targets of the intrinsically photosensitive retinal ganglion cells. Blockade with a selective antagonist reveals the respectively inhibitory and stimulatory effect of prokineticin 2 signaling on the arousal levels for the nocturnal mouse and the diurnal monkey. Thus, the mammalian diurnality or nocturnality is likely determined by the differential signaling of prokineticin 2 from the intrinsically photosensitive retinal ganglion cells onto their retinorecipient brain targets.

  10. Role of basal stress hormones and amygdala dimensions in stress coping strategies of male rhesus monkeys in response to a hazard-reward conflict

    Directory of Open Access Journals (Sweden)

    Elaheh Tekieh

    2017-08-01

    Full Text Available Objective(s: In the present study the effect of stress on monkeys that had learned to retrieve food from a five-chamber receptacle, as well as the relationship between their behavior and the serum cortisol and epinephrine levels and relative size of the amygdala was evaluated. Materials and Methods: Six male rhesus monkeys were individually given access to the food reward orderly. They could easily retrieve the rewards from all chambers except for the chamber 4, which a brief, mild electric shock (3 V was delivered to them upon touching the chamber’s interior. The coping behaviors were video-recorded and analyzed offline. Baseline serum cortisol and epinephrine levels were measured before the experiments using monkey enzyme-linked immunosorbent assay kit. One week after the behavioral experiment, the monkeys’ brains were scanned using magnetic resonance imaging under general anesthesia. The cross-sectional area of the left amygdala in sagittal plane relative to the area of the whole brain in the same slice was evaluated by the planimetric method using ImageJ software. Results: Exposure to the distressing condition caused different behavioral responses. Monkeys with higher baseline levels of serum cortisol and epinephrine and larger amygdala behaved more violently in the face of stress, indicating adopting emotion-focused stress-coping strategies. Conversely, those with low plasma epinephrine, moderate cortisol, and smaller amygdala showed perseverative behavior, indicating a problem-focused coping style. Conclusion: In dealing with the same stress, different responses might be observed from nonhuman primates according to their cortisol and epinephrine levels as well as their amygdala dimensions.

  11. Safety study of the Bio-10-SAD Bern strain of the rabies virus on the rhesus macaque monkey species

    Directory of Open Access Journals (Sweden)

    Vladimír Vrzal

    2013-01-01

    Full Text Available Based on a WHO recommendation, residual pathogenicity of the Bio-10-SAD Bern rabies virus strain (component of the Lysvulpen por. ad us. vet. vaccine was tested on rhesus macaque monkeys. Each of the ten monkeys, females, two years old, was administered orally 2 ml × 109 TCID50 of the Bio-10-SAD Bern rabies strain. The animals were monitored for 90 days. Subsequently, the animals were sacrificed and their brains were examined for presence of the vaccination rabies virus by the immunofluorescence and PCR methods. The occurrence of anti-rabies antibodies prior to and following administration of the vaccination rabies virus was also evaluated. No clinical signs of rabies were observed nor did any of the animals die of rabies following application of the virus. No rabies was detected in the study animals by post mortem examination. All of the 10 animals developed anti-rabies antibodies during the 90 days following administration of the rabies virus. It can be concluded, that Bio-10-SAD Bern virus administered at a dose equal to the tenfold maximum dose specified for field uses is safe to monkeys of the rhesus macaque species. This study is the first of its type performed in rhesus macaque monkey species.

  12. Chronic suppression of testicular function by constant infusion of gonadotropin-releasing hormone agonist and testosterone supplementation in the bonnet monkey (Macaca radiata).

    Science.gov (United States)

    Ravindranath, N; Ramesh, V; Krishnamurthy, H N; Rao, A J; Moudgal, R N

    1992-03-01

    To study the efficacy of long-term buserelin acetate infusion to desensitize pituitary and block testicular function in adult male monkeys (Macaca radiata). Proven fertile male monkeys exhibiting normal testicular function. Each of the control (n = 5) and experimental monkeys (n = 10) received a fresh miniosmotic pump every 21 days, whereas pumps in controls delivered vehicle of experimentals released 50 micrograms buserelin acetate every 24 hours. On day 170 (renewed every 60 days) a silastic capsule containing crystalline testosterone (T) was implanted in the experimental monkeys. At the end of 3 years, treatment was stopped, and recovery of testicular function and fertility monitored. (1) Treatment resulted in marked reduction of nocturnal but not basal serum T; (2) the pituitary remained desensitized to buserelin acetate throughout the 3-year period; (3) animals were largely azoospermic with occasional oligospermia exhibited by two monkeys; and (4) withdrawal of treatment restored testicular function, with 70% of animals regaining fertility. Long-term infertility (but restorable) can be induced in male monkeys by constant infusion of buserelin acetate and T.

  13. Prenatal methylmercury exposure affects spatial vision in adult monkeys

    International Nuclear Information System (INIS)

    Burbacher, Thomas M.; Grant, Kimberly S.; Mayfield, David B.; Gilbert, Steven G.; Rice, Deborah C.

    2005-01-01

    Decades of research have demonstrated that exposure to methylmercury (MeHg), a ubiquitous environmental pollutant, can have both early and long-term neurobehavioral consequences in exposed offspring. The present study assessed visual functioning in adult macaque monkeys (Macaca fascicularis) exposed in utero to 0, 50, 70, or 90 μg/kg/day of MeHg hydroxide. Twenty-one full-term, normal birth weight offspring (9 controls, 12 exposed) were tested at approximately 11-14.5 years of age on a visual contrast sensitivity task. A forced-choice tracking procedure was utilized with spatial frequencies of 1, 4, 10, and 20 cycles per degree of visual angle. On each test session, a single spatial frequency was presented across five levels of contrast, each differing by 3 dB. Methylmercury-exposed monkeys exhibited reduced contrast sensitivity thresholds, particularly at the higher spatial frequencies. The degree of visual impairment was not related to MeHg body burden or clearance and almost half of the exposed animals were unimpaired. The results from this study demonstrate that chronic in utero MeHg exposure, at subclinical levels, is associated with permanent adverse effects on spatial vision in adult monkeys

  14. Monkey prefrontal neurons during Sternberg task performance: full contents of working memory or most recent item?

    Science.gov (United States)

    Konecky, R O; Smith, M A; Olson, C R

    2017-06-01

    To explore the brain mechanisms underlying multi-item working memory, we monitored the activity of neurons in the dorsolateral prefrontal cortex while macaque monkeys performed spatial and chromatic versions of a Sternberg working-memory task. Each trial required holding three sequentially presented samples in working memory so as to identify a subsequent probe matching one of them. The monkeys were able to recall all three samples at levels well above chance, exhibiting modest load and recency effects. Prefrontal neurons signaled the identity of each sample during the delay period immediately following its presentation. However, as each new sample was presented, the representation of antecedent samples became weak and shifted to an anomalous code. A linear classifier operating on the basis of population activity during the final delay period was able to perform at approximately the level of the monkeys on trials requiring recall of the third sample but showed a falloff in performance on trials requiring recall of the first or second sample much steeper than observed in the monkeys. We conclude that delay-period activity in the prefrontal cortex robustly represented only the most recent item. The monkeys apparently based performance of this classic working-memory task on some storage mechanism in addition to the prefrontal delay-period firing rate. Possibilities include delay-period activity in areas outside the prefrontal cortex and changes within the prefrontal cortex not manifest at the level of the firing rate. NEW & NOTEWORTHY It has long been thought that items held in working memory are encoded by delay-period activity in the dorsolateral prefrontal cortex. Here we describe evidence contrary to that view. In monkeys performing a serial multi-item working memory task, dorsolateral prefrontal neurons encode almost exclusively the identity of the sample presented most recently. Information about earlier samples must be encoded outside the prefrontal cortex or

  15. Human Adipose Tissue Derived Extracellular Matrix and Methylcellulose Hydrogels Augments and Regenerates the Paralyzed Vocal Fold.

    Science.gov (United States)

    Kim, Dong Wook; Kim, Eun Ji; Kim, Eun Na; Sung, Myung Whun; Kwon, Tack-Kyun; Cho, Yong Woo; Kwon, Seong Keun

    2016-01-01

    Vocal fold paralysis results from various etiologies and can induce voice changes, swallowing complications, and issues with aspiration. Vocal fold paralysis is typically managed using injection laryngoplasty with fat or synthetic polymers. Injection with autologous fat has shown excellent biocompatibility. However, it has several disadvantages such as unpredictable resorption rate, morbidities associated with liposuction procedure which has to be done in operating room under general anesthesia. Human adipose-derived extracellular matrix (ECM) grafts have been reported to form new adipose tissue and have greater biostability than autologous fat graft. Here, we present an injectable hydrogel that is constructed from adipose tissue derived soluble extracellular matrix (sECM) and methylcellulose (MC) for use in vocal fold augmentation. Human sECM derived from adipose tissue was extracted using two major steps-ECM was isolated from human adipose tissue and was subsequently solubilized. Injectable sECM/MC hydrogels were prepared by blending of sECM and MC. Sustained vocal fold augmentation and symmetric vocal fold vibration were accomplished by the sECM/MC hydrogel in paralyzed vocal fold which were confirmed by laryngoscope, histology and a high-speed imaging system. There were increased number of collagen fibers and fatty granules at the injection site without significant inflammation or fibrosis. Overall, these results indicate that the sECM/MC hydrogel can enhance vocal function in paralyzed vocal folds without early resorption and has potential as a promising material for injection laryngoplasty for stable vocal fold augmentation which can overcome the shortcomings of autologous fat such as unpredictable duration and morbidity associated with the fat harvest.

  16. Promoter methylation and age-related downregulation of Klotho in rhesus monkey.

    Science.gov (United States)

    King, Gwendalyn D; Rosene, Douglas L; Abraham, Carmela R

    2012-12-01

    While overall DNA methylation decreases with age, CpG-rich areas of the genome can become hypermethylated. Hypermethylation near transcription start sites typically decreases gene expression. Klotho (KL) is important in numerous age-associated pathways including insulin/IGF1 and Wnt signaling and naturally decreases with age in brain, heart, and liver across species. Brain tissues from young and old rhesus monkeys were used to determine whether epigenetic modification of the KL promoter underlies age-related decreases in mRNA and protein levels of KL. The KL promoter in genomic DNA from brain white matter did not show evidence of oxidation in vivo but did exhibit an increase in methylation with age. Further analysis identified individual CpG motifs across the region of interest with increased methylation in old animals. In vitro methyl modification of these individual cytosine residues confirmed that methylation of the promoter can decrease gene transcription. These results provide evidence that changes in KL gene expression with age may, at least in part, be the result of epigenetic changes to the 5' regulatory region.

  17. Subarachnoid administration of iohexol in cynomolgus monkeys

    International Nuclear Information System (INIS)

    Drobeck, H.P.; Mayes, B.A.; Barbolt, T.A.; Fabian, R.J.; Kimball, J.P.; Slighter, R.R. Jr.

    1986-01-01

    A non-ionic diagnostic medium, iohexol, was administered by subarachnoid injection to groups of six cynomolgus monkeys and compared with the vehicle, physiologically normal saline, and/or saline of equal osmolality to determine its potential for increasing total protein and leucocyte levels in cerebrospinal fluid. Also investigated was the effect of repeated spinal taps not subsequently followed by the intrathecal injection of test or control articles. In the monkey, unlike man, low-level leucocyte counts were consistently observed following initial withdrawal of spinal fluid. Elevated leucocyte and total protein levels were observed in the present investigations one day to a week after intrathecal injection of radiopaque, vehicle or saline solution. Total protein returned to normal levels earlier than did leucocyte counts. However, repeated needle puncture alone was found to be sufficient to cause an elevation of leucocytes 3 to 4 times the baseline level, while inflammatory effects were observed histologically only when autopsy was performed soon after the final spinal tap. (orig.)

  18. Near-term and late biological effects of acute and low-dose-rate continuous gamma-ray exposure in dogs and monkeys

    International Nuclear Information System (INIS)

    Spalding, J.F.; Holland, L.M.

    1979-07-01

    Monkeys (Macaca mulatta) and dogs (beagle) were given thirteen 100-rad gamma-ray doses at 28-day intervals. The comparative response (inury and recovery) of the hematopoietic system of the two species was observed at 7-day intervals during the exposure regime. At 84 days after the thirteenth gamma-ray dose, the 1300-rad conditioned and control dogs and monkeys were challenged continuously with gamma rays at 35 r/day until death to determine the amount of radiation-induced injry remaining in conditioned animals as a reduction in mean survival time. Dogs (50%) and monkeys (8%) died from injury incurred during conditioning exposures. Thus, the comparative response (in terms of lethality) of dogs and monkeys to dose protraction by acute dose fractionation was similar to what we would expect from a single acute dose. The mean survival times for nonconditioned dogs and monkeys during continuous exposure at 35 R/day were the same (approx. 1400 h). Thus, the hematopoietic response of the two species by this method of dose protraction was not significantly different. Mean survival times of conditioned dogs and monkeys during the continuous 35-R/day gamma-ray challenge exposure were greater (significant in dogs but not in monkeys) than for their control counterparts. Thus, long-term radiation-induced injury was not measurable by this method. Conditioning doses of more than 4 times the acute LD 50 30 in dogs and approximately 2 times that in monkeys served only to increase both mean survival time and variance in a gamma-ray stress environment with a dose rate of 35 Rat/day

  19. Sterile protection against Plasmodium knowlesi in rhesus monkeys from a malaria vaccine: comparison of heterologous prime boost strategies.

    Directory of Open Access Journals (Sweden)

    George Jiang

    Full Text Available Using newer vaccine platforms which have been effective against malaria in rodent models, we tested five immunization regimens against Plasmodium knowlesi in rhesus monkeys. All vaccines included the same four P. knowlesi antigens: the pre-erythrocytic antigens CSP, SSP2, and erythrocytic antigens AMA1, MSP1. We used four vaccine platforms for prime or boost vaccinations: plasmids (DNA, alphavirus replicons (VRP, attenuated adenovirus serotype 5 (Ad, or attenuated poxvirus (Pox. These four platforms combined to produce five different prime/boost vaccine regimens: Pox alone, VRP/Pox, VRP/Ad, Ad/Pox, and DNA/Pox. Five rhesus monkeys were immunized with each regimen, and five Control monkeys received a mock vaccination. The time to complete vaccinations was 420 days. All monkeys were challenged twice with 100 P. knowlesi sporozoites given IV. The first challenge was given 12 days after the last vaccination, and the monkeys receiving the DNA/Pox vaccine were the best protected, with 3/5 monkeys sterilely protected and 1/5 monkeys that self-cured its parasitemia. There was no protection in monkeys that received Pox malaria vaccine alone without previous priming. The second sporozoite challenge was given 4 months after the first. All 4 monkeys that were protected in the first challenge developed malaria in the second challenge. DNA, VRP and Ad5 vaccines all primed monkeys for strong immune responses after the Pox boost. We discuss the high level but short duration of protection in this experiment and the possible benefits of the long interval between prime and boost.

  20. Species differences in blood-brain barrier transport of three positron emission tomography radioligands with emphasis on P-glycoprotein transport

    DEFF Research Database (Denmark)

    Syvanen, S.; Lindhe, O.; Palner, M.

    2009-01-01

    preclinical data to humans. Compounds found to be P-gp substrates in rodents are likely to also be substrates in higher species, but sufficient blood-brain barrier permeability may be retained in humans to allow the compound to act at intracerebral targets Udgivelsesdato: 2009/3......Species differences occur in the brain concentrations of drugs, but the reasons for these differences are not yet apparent. This study was designed to compare brain uptake of three radiolabeled P-glycoprotein (P-gp) substrates across species using positron emission tomography. Brain concentrations...... and brain-to-plasma ratios were compared; [(11)C]verapamil in rats, guinea pigs, and monkeys; [(11)C](S)-(2-methoxy-5-(5-trifluoromethyltetrazol-1-yl)-phenylmethylamino )-2(S)-phenylpiperidine (GR205171) in rats, guinea pigs, monkeys, and humans; and [(18)F]altanserin in rats, minipigs, and humans...

  1. Radiation-induced emesis in monkeys

    International Nuclear Information System (INIS)

    Mattsson, J.L.; Yochmowitz, M.G.

    1980-01-01

    To determine the emesis ED 50 for 60 Co radiation, 15 male rhesus monkeys were exposed to whole-body radiation doses ranging from 350 to 550 rad midline tissue dose. An up-and-down sequence of exposures was used. Step size between doses was 50 rad, and dose rate was 20 rad/min. There had been no access to food for 1 to 2 h. The ED 50 +- SE was found to be 446 +- 27 rad. To determine the effect of motion on emesis ED 50 , six more monkeys were exposed to 60 Co radiation as above, except that the chair in which they were seated was oscillated forward and backward 5 to 15 0 (pitch axis) at a variable rate not exceeding 0.3 Hz. Radioemesis ED 50 +- SE with motion was 258 +- 19 rad, a value significantly lower (P < 0.01) than for stationary monkeys

  2. Wireless brain-machine interface using EEG and EOG: brain wave classification and robot control

    Science.gov (United States)

    Oh, Sechang; Kumar, Prashanth S.; Kwon, Hyeokjun; Varadan, Vijay K.

    2012-04-01

    A brain-machine interface (BMI) links a user's brain activity directly to an external device. It enables a person to control devices using only thought. Hence, it has gained significant interest in the design of assistive devices and systems for people with disabilities. In addition, BMI has also been proposed to replace humans with robots in the performance of dangerous tasks like explosives handling/diffusing, hazardous materials handling, fire fighting etc. There are mainly two types of BMI based on the measurement method of brain activity; invasive and non-invasive. Invasive BMI can provide pristine signals but it is expensive and surgery may lead to undesirable side effects. Recent advances in non-invasive BMI have opened the possibility of generating robust control signals from noisy brain activity signals like EEG and EOG. A practical implementation of a non-invasive BMI such as robot control requires: acquisition of brain signals with a robust wearable unit, noise filtering and signal processing, identification and extraction of relevant brain wave features and finally, an algorithm to determine control signals based on the wave features. In this work, we developed a wireless brain-machine interface with a small platform and established a BMI that can be used to control the movement of a robot by using the extracted features of the EEG and EOG signals. The system records and classifies EEG as alpha, beta, delta, and theta waves. The classified brain waves are then used to define the level of attention. The acceleration and deceleration or stopping of the robot is controlled based on the attention level of the wearer. In addition, the left and right movements of eye ball control the direction of the robot.

  3. Effects of cholinergic deafferentation of the rhinal cortex on visual recognition memory in monkeys.

    Science.gov (United States)

    Turchi, Janita; Saunders, Richard C; Mishkin, Mortimer

    2005-02-08

    Excitotoxic lesion studies have confirmed that the rhinal cortex is essential for visual recognition ability in monkeys. To evaluate the mnemonic role of cholinergic inputs to this cortical region, we compared the visual recognition performance of monkeys given rhinal cortex infusions of a selective cholinergic immunotoxin, ME20.4-SAP, with the performance of monkeys given control infusions into this same tissue. The immunotoxin, which leads to selective cholinergic deafferentation of the infused cortex, yielded recognition deficits of the same magnitude as those produced by excitotoxic lesions of this region, providing the most direct demonstration to date that cholinergic activation of the rhinal cortex is essential for storing the representations of new visual stimuli and thereby enabling their later recognition.

  4. Non-invasive brain-computer interface system: towards its application as assistive technology.

    Science.gov (United States)

    Cincotti, Febo; Mattia, Donatella; Aloise, Fabio; Bufalari, Simona; Schalk, Gerwin; Oriolo, Giuseppe; Cherubini, Andrea; Marciani, Maria Grazia; Babiloni, Fabio

    2008-04-15

    The quality of life of people suffering from severe motor disabilities can benefit from the use of current assistive technology capable of ameliorating communication, house-environment management and mobility, according to the user's residual motor abilities. Brain-computer interfaces (BCIs) are systems that can translate brain activity into signals that control external devices. Thus they can represent the only technology for severely paralyzed patients to increase or maintain their communication and control options. Here we report on a pilot study in which a system was implemented and validated to allow disabled persons to improve or recover their mobility (directly or by emulation) and communication within the surrounding environment. The system is based on a software controller that offers to the user a communication interface that is matched with the individual's residual motor abilities. Patients (n=14) with severe motor disabilities due to progressive neurodegenerative disorders were trained to use the system prototype under a rehabilitation program carried out in a house-like furnished space. All users utilized regular assistive control options (e.g., microswitches or head trackers). In addition, four subjects learned to operate the system by means of a non-invasive EEG-based BCI. This system was controlled by the subjects' voluntary modulations of EEG sensorimotor rhythms recorded on the scalp; this skill was learnt even though the subjects have not had control over their limbs for a long time. We conclude that such a prototype system, which integrates several different assistive technologies including a BCI system, can potentially facilitate the translation from pre-clinical demonstrations to a clinical useful BCI.

  5. Dissociation of item and source memory in rhesus monkeys.

    Science.gov (United States)

    Basile, Benjamin M; Hampton, Robert R

    2017-09-01

    Source memory, or memory for the context in which a memory was formed, is a defining characteristic of human episodic memory and source memory errors are a debilitating symptom of memory dysfunction. Evidence for source memory in nonhuman primates is sparse despite considerable evidence for other types of sophisticated memory and the practical need for good models of episodic memory in nonhuman primates. A previous study showed that rhesus monkeys confused the identity of a monkey they saw with a monkey they heard, but only after an extended memory delay. This suggests that they initially remembered the source - visual or auditory - of the information but forgot the source as time passed. Here, we present a monkey model of source memory that is based on this previous study. In each trial, monkeys studied two images, one that they simply viewed and touched and the other that they classified as a bird, fish, flower, or person. In a subsequent memory test, they were required to select the image from one source but avoid the other. With training, monkeys learned to suppress responding to images from the to-be-avoided source. After longer memory intervals, monkeys continued to show reliable item memory, discriminating studied images from distractors, but made many source memory errors. Monkeys discriminated source based on study method, not study order, providing preliminary evidence that our manipulation of retention interval caused errors due to source forgetting instead of source confusion. Finally, some monkeys learned to select remembered images from either source on cue, showing that they did indeed remember both items and both sources. This paradigm potentially provides a new model to study a critical aspect of episodic memory in nonhuman primates. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Self-Paced (Asynchronous BCI Control of a Wheelchair in Virtual Environments: A Case Study with a Tetraplegic

    Directory of Open Access Journals (Sweden)

    Robert Leeb

    2007-09-01

    Full Text Available The aim of the present study was to demonstrate for the first time that brain waves can be used by a tetraplegic to control movements of his wheelchair in virtual reality (VR. In this case study, the spinal cord injured (SCI subject was able to generate bursts of beta oscillations in the electroencephalogram (EEG by imagination of movements of his paralyzed feet. These beta oscillations were used for a self-paced (asynchronous brain-computer interface (BCI control based on a single bipolar EEG recording. The subject was placed inside a virtual street populated with avatars. The task was to “go” from avatar to avatar towards the end of the street, but to stop at each avatar and talk to them. In average, the participant was able to successfully perform this asynchronous experiment with a performance of 90%, single runs up to 100%.

  7. Brain Computer Interface-Controlling Devices Utilizing The Alpha Brain Waves

    Directory of Open Access Journals (Sweden)

    Rohan Hundia

    2015-01-01

    Full Text Available Abstract This paper describes the development and testing of an interface system whereby one can control external devices by voluntarily controlling alpha waves that is through eye movement. Such a system may be used for the control of prosthetics robotic arms and external devices like wheelchairs using the alpha brain waves and the Mu rhythm. The response generated through the movement of the eye detecting and controlling the amplitude of the alpha brain waves is interfaced and processed to control Robotic systems and smart home control. In order to measure the response of alpha waves over different lobes of the brain initially I measured these signals over 32 regions using silver chloride plated electrodes. By the opening and the closure of the eyes and the movement in the up-down left-right directions and processing these movements measuring them over the occipital region I was able to differentiate the amplitude of the alpha waves generated due to these several movements. In the First session testing period subjects were asked to close and open their eyes and they were able to control limited movements of a Robot and a prosthetic arm. In the Second 2session the movement of the eyes was also considered left-right up-down along with the opening and closure during this time span they were able to control more dimensions of the robot several devices at the same time using different eye movements.

  8. Absorption, Distribution, and Excretion of 14C-APX001 after Single-Dose Administration to Rats and Monkeys

    Science.gov (United States)

    Mansbach, Robert; Shaw, Karen J; Hodges, Michael R; Coleman, Samantha; Fitzsimmons, Michael E

    2017-01-01

    Abstract Background APX001 is a small-molecule therapeutic agent in clinical development for the treatment of invasive fungal infections (IFI). Methods The absorption, distribution and excretion profiles of [14C]APX001-derived radioactivity were determined in rats (albino and pigmented) and monkeys. Rats (some implanted with bile duct cannulae) were administered a single 100 mg/kg oral dose or a 30 mg/kg intravenous (IV) dose. Monkeys were administered a single 6 mg/kg IV dose. Samples of blood, urine, feces and bile, as well as carcasses, were collected through 168 hours after dosing. Samples were analyzed for total radioactivity content by liquid scintillation counting, and carcasses were analyzed by quantitative whole-body autoradiography. Results [14C]APX001-derived radioactivity was rapidly and extensively absorbed and extensively distributed to most tissues for both routes of administration in both species. In rats, tissues with the highest radioactivity Cmax values included bile, abdominal fat, reproductive fat, subcutaneous fat, and liver, but radioactivity was also detected in tissues associated with IFI, including lung, brain and eye. In monkeys, the highest Cmax values were in bile, urine, uveal tract, bone marrow, abdominal fat, liver, and kidney cortex. Liver and kidney were the tissues with highest radioactivity, but as in the rat, radioactivity was also detected in lung, brain and eye tissues. In pigmented rats, radiocarbon was densely distributed into pigmented tissue and more slowly cleared than from other tissues. Mean recovery of radioactivity in rats was approximately 95–100%. In bile duct-intact rats, >90% of radioactivity was recovered in feces. In cannulated rats, biliary excretion of radioactivity was the major route of elimination and accounted for 88.8% of the dose, whereas urinary and fecal excretion of radioactivity was minor and accounted for 2.56% and 5.42% of the dose, respectively. In monkeys, the overall recovery of radioactivity

  9. Depth perception from moving cast shadow in macaque monkey.

    Science.gov (United States)

    Mizutani, Saneyuki; Usui, Nobuo; Yokota, Takanori; Mizusawa, Hidehiro; Taira, Masato; Katsuyama, Narumi

    2015-07-15

    In the present study, we investigate whether the macaque monkey can perceive motion in depth using a moving cast shadow. To accomplish this, we conducted two experiments. In the first experiment, an adult Japanese monkey was trained in a motion discrimination task in depth by binocular disparity. A square was presented on the display so that it appeared with a binocular disparity of 0.12 degrees (initial position), and moved toward (approaching) or away from (receding) the monkey for 1s. The monkey was trained to discriminate the approaching and receding motion of the square by GO/delayed GO-type responses. The monkey showed a significantly high accuracy rate in the task, and the performance was maintained when the position, color, and shape of the moving object were changed. In the next experiment, the change in the disparity was gradually decreased in the motion discrimination task. The results showed that the performance of the monkey declined as the distance of the approaching and receding motion of the square decreased from the initial position. However, when a moving cast shadow was added to the stimulus, the monkey responded to the motion in depth induced by the cast shadow in the same way as by binocular disparity; the reward was delivered randomly or given in all trials to prevent the learning of the 2D motion of the shadow in the frontal plane. These results suggest that the macaque monkey can perceive motion in depth using a moving cast shadow as well as using binocular disparity. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Brain-controlled body movement assistance devices and methods

    Energy Technology Data Exchange (ETDEWEB)

    Leuthardt, Eric C.; Love, Lonnie J.; Coker, Rob; Moran, Daniel W.

    2017-01-10

    Methods, devices, systems, and apparatus, including computer programs encoded on a computer storage medium, for brain-controlled body movement assistance devices. In one aspect, a device includes a brain-controlled body movement assistance device with a brain-computer interface (BCI) component adapted to be mounted to a user, a body movement assistance component operably connected to the BCI component and adapted to be worn by the user, and a feedback mechanism provided in connection with at least one of the BCI component and the body movement assistance component, the feedback mechanism being configured to output information relating to a usage session of the brain-controlled body movement assistance device.

  11. Induction of Encephalitis in Rhesus Monkeys Infused with Lymphocryptovirus-Infected B-Cells Presenting MOG34–56 Peptide

    Science.gov (United States)

    Haanstra, Krista G.; Wubben, Jacqueline A. M.; Jonker, Margreet; Hart, Bert A. ‘t.

    2013-01-01

    The overlapping epidemiology of multiple sclerosis (MS) and Epstein-Barr virus (EBV), the increased risk to develop MS after infectious mononucleosis (IM) and the localization of EBV-infected B-cells within the MS brain suggest a causal link between EBV and MS. However, the underlying mechanism is unknown. We hypothesize that EBV-infected B-cells are capable of eliciting a central nervous system (CNS) targeting autoimmune reaction. To test this hypothesis we have developed a novel experimental model in rhesus monkeys of IM-like disease induced by infusing autologous B-lymphoblastoid cells (B-LCL). Herpesvirus papio (HVP) is a lymphocryptovirus related to EBV and was used to generate rhesus monkey B-LCL. Three groups of five animals were included; each group received three intravenous infusions of B-LCL that were either pulsed with the encephalitogenic self peptide MOG34–56 (group A), a mimicry peptide (981–1003) of the major capsid protein of cytomegalovirus (CMVmcp981–1003; group B) or the citrullinated MOG34–56 (cMOG34–56; group C). Groups A and B received on day 98 a single immunization with MOG34–56 in incomplete Freund’s adjuvant (IFA). Group C monkeys were euthanized just prior to day 98 without booster immunization. We observed self-peptide-specific proliferation of T-cells, superimposed on similar strong proliferation of CD3+CD8+ T-cells against the B-LCL as observed in IM. The brains of several monkeys contained perivascular inflammatory lesions of variable size, comprising CD3+ and CD68+ cells. Moreover, clusters of CD3+ and CD20+ cells were detected in the meninges. The only evident clinical sign was substantial loss of bodyweight (>15%), a symptom observed both in early autoimmune encephalitis and IM. In conclusion, this model suggests that EBV-induced B-LCL can elicit a CNS targeting inflammatory (auto)immune reaction. PMID:23977076

  12. Susceptibility and lack of evidence for a viremic state of rabies in the night owl monkey, Aotus nancymaae

    Directory of Open Access Journals (Sweden)

    Reaves Erik J

    2012-05-01

    Full Text Available Abstract Background Rabies causes an acute fatal encephalomyelitis in most mammals following infection with rhabdovirus of the genus Lyssavirus. Little is known about rabies virus infection in species of New World non-human Primates (NHP. To investigate the suitability of the owl monkey Aotus nancymaae asissue sections examined were unremarkable for inflammation or other histologic signs of rabies a viable animal model for rabies virus candidate vaccine testing, we used clinical presentation, serology, viral isolation, and PCR to evaluate the incubation period, immunity, and pathogenesis of infected animals. We tested the hypothesis that no viremic state exists for rabies virus. Methods Eight monkeys divided into two equal groups were inoculated intramuscularly either in the neck or footpad with 105 pfu of rabies virus (Pasteur/V-13R and observed for >130 days. Oral and blood samples were collected and analyzed. Results Two monkeys inoculated in the neck displayed classic paralytic rabies. The mean incubation period was 11.5 days. The average maximum IgG response (antibody titer >0.200 O.D. was achieved at day 10.0 and 62.3 in the clinical rabies and non-clinical rabies cases, respectively (p = 0.0429. No difference in IgM or IgG time to seroconversion or average maximum IgM level was observed between neck versus footpad inoculation groups. No viremia or viral shedding was detected by PCR or viral isolation during the observation period, including within the two symptomatic animals three days after disease onset. Tissue sections examined were unremarkable for inflammation or other histologic signs of rabies within the asymptomatic animal. Similarly none of the brain sections exhibited immunoreactivity for rabies virus antibody. Discussion This study demonstrates there is no difference in time to immune response between inoculation sites and distance to the brain; however, immune response tends to be more rapid in cases of clinically

  13. Analogical reasoning in a capuchin monkey (Cebus apella).

    Science.gov (United States)

    Kennedy, Erica Hoy; Fragaszy, Dorothy M

    2008-05-01

    Previous evidence has suggested that analogical reasoning (recognizing similarities among object relations when the objects themselves are dissimilar) is limited to humans and apes. This study investigated whether capuchin monkeys (Cebus apella) can use analogical reasoning to solve a 3-dimensional search task. The task involved hiding a food item under 1 of 2 or 3 plastic cups of different sizes and then allowing subjects to search for food hidden under the cup of analogous size in their own set of cups. Four monkeys were exposed to a series of relational matching tasks. If subjects reached criterion on these tasks, they were exposed to relational transfer tasks involving novel stimuli. Three of the monkeys failed to reach criterion on the basic relational matching tasks and therefore were not tested further. One monkey, however, revealed above-chance performance on a series of transfer tasks with 3 novel stimuli. This evidence suggests that contrary to previous arguments, a member of a New World monkey species can solve an analogical problem. PsycINFO Database Record (c) 2008 APA, all rights reserved.

  14. Neonatal face-to-face interactions promote later social behaviour in infant rhesus monkeys

    Science.gov (United States)

    Dettmer, Amanda M.; Kaburu, Stefano S. K.; Simpson, Elizabeth A.; Paukner, Annika; Sclafani, Valentina; Byers, Kristen L.; Murphy, Ashley M.; Miller, Michelle; Marquez, Neal; Miller, Grace M.; Suomi, Stephen J.; Ferrari, Pier F.

    2016-01-01

    In primates, including humans, mothers engage in face-to-face interactions with their infants, with frequencies varying both within and across species. However, the impact of this variation in face-to-face interactions on infant social development is unclear. Here we report that infant monkeys (Macaca mulatta) who engaged in more neonatal face-to-face interactions with mothers have increased social interactions at 2 and 5 months. In a controlled experiment, we show that this effect is not due to physical contact alone: monkeys randomly assigned to receive additional neonatal face-to-face interactions (mutual gaze and intermittent lip-smacking) with human caregivers display increased social interest at 2 months, compared with monkeys who received only additional handling. These studies suggest that face-to-face interactions from birth promote young primate social interest and competency. PMID:27300086

  15. Monkey-derived monoclonal antibodies against Plasmodium falciparum

    International Nuclear Information System (INIS)

    Stanley, H.A.; Reese, R.T.

    1985-01-01

    A system has been developed that allows efficient production of monkey monoclonal antibodies from owl monkeys. Splenocytes or peripheral blood lymphocytes from monkeys immune to the human malarial parasite, Plasmodium falciparum, were fused with P3X63 Ag8.653 mouse myelomas. The resulting hybridomas were screened by an indirect fluorescent antibody test for the production of monkey monoclonal antibodies (mAb) reactive with P. falciparum. Most of the mAb reacted with the P. falciparum merozoites and immunoprecipitated a parasite-derived glycoprotein having a relative molecular weight of 185,000. These mAb gave a minimum of five different immunoprecipitation patterns, thus demonstrating that a large number of polypeptides obtained when parasitized erythrocytes are solubilized share epitopes with this large glycoprotein. In addition, mAb were obtained that reacted with antigens associated with the infected erythrocyte membrane. One of these mAb bound a M/sub r/ 95,000 antigen. Radioimmunoprecipitation assays using 125 T-antibodies were done

  16. Accumulation, biotransformation, histopathology and paralysis in the Pacific calico scallop Argopecten ventricosus by the paralyzing toxins of the dinoflagellate Gymnodinium catenatum.

    Science.gov (United States)

    Escobedo-Lozano, Amada Y; Estrada, Norma; Ascencio, Felipe; Contreras, Gerardo; Alonso-Rodriguez, Rosalba

    2012-05-01

    The dinoflagellate Gymnodinium catenatum produces paralyzing shellfish poisons that are consumed and accumulated by bivalves. We performed short-term feeding experiments to examine ingestion, accumulation, biotransformation, histopathology, and paralysis in the juvenile Pacific calico scallop Argopecten ventricosus that consume this dinoflagellate. Depletion of algal cells was measured in closed systems. Histopathological preparations were microscopically analyzed. Paralysis was observed and the time of recovery recorded. Accumulation and possible biotransformation of toxins were measured by HPLC analysis. Feeding activity in treated scallops showed that scallops produced pseudofeces, ingestion rates decreased at 8 h; approximately 60% of the scallops were paralyzed and melanin production and hemocyte aggregation were observed in several tissues at 15 h. HPLC analysis showed that the only toxins present in the dinoflagellates and scallops were the N-sulfo-carbamoyl toxins (C1, C2); after hydrolysis, the carbamate toxins (epimers GTX2/3) were present. C1 and C2 toxins were most common in the mantle, followed by the digestive gland and stomach-complex, adductor muscle, kidney and rectum group, and finally, gills. Toxin profiles in scallop tissue were similar to the dinoflagellate; biotransformations were not present in the scallops in this short-term feeding experiment.

  17. Distribution and abundance of sacred monkeys in Igboland, southern Nigeria.

    Science.gov (United States)

    Baker, Lynne R; Tanimola, Adebowale A; Olubode, Oluseun S; Garshelis, David L

    2009-07-01

    Although primates are hunted on a global scale, some species are protected against harassment and killing by taboos or religious doctrines. Sites where the killing of sacred monkeys or the destruction of sacred groves is forbidden may be integral to the conservation of certain species. In 2004, as part of a distribution survey of Sclater's guenon (Cercopithecus sclateri) in southern Nigeria, we investigated reports of sacred monkeys in the Igbo-speaking region of Nigeria. We confirmed nine new sites where primates are protected as sacred: four with tantalus monkeys (Chlorocebus tantalus) and five with mona monkeys (Cercopithecus mona). During 2004-2006, we visited two communities (Akpugoeze and Lagwa) previously known to harbor sacred populations of Ce. sclateri to estimate population abundance and trends. We directly counted all groups and compared our estimates with previous counts when available. We also estimated the size of sacred groves and compared these with grove sizes reported in the literature. The mean size of the sacred groves in Akpugoeze (2.06 ha, n = 10) was similar to others in Africa south of the Sahel, but larger than the average grove in Lagwa (0.49 ha, n = 15). We estimated a total population of 124 Sclater's monkeys in 15 groups in Lagwa and 193 monkeys in 20 groups in Akpugoeze. The Akpugoeze population was relatively stable over two decades, although the proportion of infants declined, and the number of groups increased. As Sclater's monkey does not occur in any official protected areas, sacred populations are important to the species' long-term conservation. Despite the monkeys' destruction of human crops, most local people still adhere to the custom of not killing monkeys. These sites represent ideal locations in which to study the ecology of Sclater's monkey and human-wildlife interactions. (c) 2009 Wiley-Liss, Inc.

  18. Clinical application of fMRI: Activation of the motor cortex in an LIS patient

    International Nuclear Information System (INIS)

    Mao, H.; Popp, C.A.; Song, A.W.; Kennedy, P.R.

    1999-01-01

    Patients suffering from the Locked-in Syndrome are completely paralyzed over their entire body, while their brain retains full consciousness. Functional magnetic resonance imaging (fMRI) is a method applied to identify those areas of the brain where activities of neurons indicate motor performance, and which might be electronically stimulated and used for controlling electronic aids expressing intended movements of the patient. (orig./CB) [de

  19. Locomotor Anatomy and Behavior of Patas Monkeys (Erythrocebus patas with Comparison to Vervet Monkeys (Cercopithecus aethiops

    Directory of Open Access Journals (Sweden)

    Adrienne L. Zihlman

    2013-01-01

    Full Text Available Patas monkeys (Erythrocebus patas living in African savanna woodlands and grassland habitats have a locomotor system that allows them to run fast, presumably to avoid predators. Long fore- and hindlimbs, long foot bones, short toes, and a digitigrade foot posture were proposed as anatomical correlates with speed. In addition to skeletal proportions, soft tissue and whole body proportions are important components of the locomotor system. To further distinguish patas anatomy from other Old World monkeys, a comparative study based on dissection of skin, muscle, and bone from complete individuals of patas and vervet monkeys (Cercopithecus aethiops was undertaken. Analysis reveals that small adjustments in patas skeletal proportions, relative mass of limbs and tail, and specific muscle groups promote efficient sagittal limb motion. The ability to run fast is based on a locomotor system adapted for long distance walking. The patas’ larger home range and longer daily range than those of vervets give them access to highly dispersed, nutritious foods, water, and sleeping trees. Furthermore, patas monkeys have physiological adaptations that enable them to tolerate and dissipate heat. These features all contribute to the distinct adaptation that is the patas monkeys’ basis for survival in grassland and savanna woodland areas.

  20. Early monocular defocus disrupts the normal development of receptive-field structure in V2 neurons of macaque monkeys.

    Science.gov (United States)

    Tao, Xiaofeng; Zhang, Bin; Shen, Guofu; Wensveen, Janice; Smith, Earl L; Nishimoto, Shinji; Ohzawa, Izumi; Chino, Yuzo M

    2014-10-08

    Experiencing different quality images in the two eyes soon after birth can cause amblyopia, a developmental vision disorder. Amblyopic humans show the reduced capacity for judging the relative position of a visual target in reference to nearby stimulus elements (position uncertainty) and often experience visual image distortion. Although abnormal pooling of local stimulus information by neurons beyond striate cortex (V1) is often suggested as a neural basis of these deficits, extrastriate neurons in the amblyopic brain have rarely been studied using microelectrode recording methods. The receptive field (RF) of neurons in visual area V2 in normal monkeys is made up of multiple subfields that are thought to reflect V1 inputs and are capable of encoding the spatial relationship between local stimulus features. We created primate models of anisometropic amblyopia and analyzed the RF subfield maps for multiple nearby V2 neurons of anesthetized monkeys by using dynamic two-dimensional noise stimuli and reverse correlation methods. Unlike in normal monkeys, the subfield maps of V2 neurons in amblyopic monkeys were severely disorganized: subfield maps showed higher heterogeneity within each neuron as well as across nearby neurons. Amblyopic V2 neurons exhibited robust binocular suppression and the strength of the suppression was positively correlated with the degree of hereogeneity and the severity of amblyopia in individual monkeys. Our results suggest that the disorganized subfield maps and robust binocular suppression of amblyopic V2 neurons are likely to adversely affect the higher stages of cortical processing resulting in position uncertainty and image distortion. Copyright © 2014 the authors 0270-6474/14/3413840-15$15.00/0.

  1. Captive spider monkeys (Ateles geoffroyi) arm-raise to solicit allo-grooming.

    Science.gov (United States)

    Scheel, Matthew H; Edwards, Dori

    2012-03-01

    Old World monkeys solicit allo-grooming from conspecifics. However, there are relatively few studies of allo-grooming among spider monkeys, and descriptions of allo-grooming solicitation among spider monkeys are anecdotal. In this study, eighty-one hours of video, shot over eight weeks, captured 271 allo-grooming bouts among small groups of captive spider monkeys. Six of eight monkeys made heretofore unreported arm-raises that solicited higher than normal rates of allo-grooming. Allo-grooming bout durations following arm-raises also tended to be longer than bouts not preceded by arm-raises. The efficacy of the arm-raise at soliciting allo-grooming suggests spider monkeys are capable of intentional communication. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Dental disorders in brown howler monkeys (Alouatta guariba clamitans) maintained in captivity.

    Science.gov (United States)

    Dias Neto, Ramiro das Neves; Fecchio, Roberto Silva; Rahal, Sheila Canevese; Teixeira, Carlos Roberto; Gioso, Marco Antônio; Pereira, Camila Trevisan; Santos, Maria Augusta Adami Pereira Dos; Milanelo, Liliane

    2016-04-01

    The aim of this study was to investigate dental disorders of brown howler monkeys maintained in captivity. The hypothesis is that the identification and diagnosis of the lesions may contribute to control and prevention. Sixteen intact brown howler monkeys (Alouatta guariba clamitans), eight females and eight males, weighing from 3.9 to 6.8 kg, were studied. Under general anesthesia, the teeth were evaluated by visual inspection, probing, palpation, and intra-oral radiographic exam. The findings were registered on a dental chart specific for primates. Of the 16 monkeys evaluated in the present study, 94% (n = 15) had some type of dental disorder. The lesions observed were dental calculus (88%), dental wear (81%), missing teeth (38%), gingivitis (19%), gingival recession (6%), dental fracture (19%), pulp exposure (19%), and dental staining (25%). Alouatta guariba clamitans maintained in captivity have a high rate of dental problems. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Metabolism of lithocholic and chenodeoxycholic acids in the squirrel monkey

    International Nuclear Information System (INIS)

    Suzuki, H.; Hamada, M.; Kato, F.

    1985-01-01

    Metabolism of lithocholic acid (LCA) and chenodeoxycholic acid (CDCA) was studied in the squirrel monkey to clarify the mechanism of the lack of toxicity of CDCA in this animal. Radioactive LCA was administered to squirrel monkeys with biliary fistula. Most radioactivity was excreted in the bile in the form of unsulfated lithocholyltaurine. The squirrel monkey thus differs from humans and chimpanzees, which efficiently sulfate LCA, and is similar to the rhesus monkey and baboon in that LCA is poorly sulfated. When labeled CDCA was orally administered to squirrel monkeys, less than 20% of the dosed radioactivity was recovered as LCA and its further metabolites in feces over 3 days, indicating that bacterial metabolism of CDCA into LCA is strikingly less than in other animals and in humans. It therefore appears that LCA, known as a hepatotoxic secondary bile acid, is not accumulated in the squirrel monkey, not because of its rapid turnover through sulfation, but because of the low order of its production

  4. Distinct neural patterns enable grasp types decoding in monkey dorsal premotor cortex

    Science.gov (United States)

    Hao, Yaoyao; Zhang, Qiaosheng; Controzzi, Marco; Cipriani, Christian; Li, Yue; Li, Juncheng; Zhang, Shaomin; Wang, Yiwen; Chen, Weidong; Chiara Carrozza, Maria; Zheng, Xiaoxiang

    2014-12-01

    Objective. Recent studies have shown that dorsal premotor cortex (PMd), a cortical area in the dorsomedial grasp pathway, is involved in grasp movements. However, the neural ensemble firing property of PMd during grasp movements and the extent to which it can be used for grasp decoding are still unclear. Approach. To address these issues, we used multielectrode arrays to record both spike and local field potential (LFP) signals in PMd in macaque monkeys performing reaching and grasping of one of four differently shaped objects. Main results. Single and population neuronal activity showed distinct patterns during execution of different grip types. Cluster analysis of neural ensemble signals indicated that the grasp related patterns emerged soon (200-300 ms) after the go cue signal, and faded away during the hold period. The timing and duration of the patterns varied depending on the behaviors of individual monkey. Application of support vector machine model to stable activity patterns revealed classification accuracies of 94% and 89% for each of the two monkeys, indicating a robust, decodable grasp pattern encoded in the PMd. Grasp decoding using LFPs, especially the high-frequency bands, also produced high decoding accuracies. Significance. This study is the first to specify the neuronal population encoding of grasp during the time course of grasp. We demonstrate high grasp decoding performance in PMd. These findings, combined with previous evidence for reach related modulation studies, suggest that PMd may play an important role in generation and maintenance of grasp action and may be a suitable locus for brain-machine interface applications.

  5. Human Adipose Tissue Derived Extracellular Matrix and Methylcellulose Hydrogels Augments and Regenerates the Paralyzed Vocal Fold.

    Directory of Open Access Journals (Sweden)

    Dong Wook Kim

    Full Text Available Vocal fold paralysis results from various etiologies and can induce voice changes, swallowing complications, and issues with aspiration. Vocal fold paralysis is typically managed using injection laryngoplasty with fat or synthetic polymers. Injection with autologous fat has shown excellent biocompatibility. However, it has several disadvantages such as unpredictable resorption rate, morbidities associated with liposuction procedure which has to be done in operating room under general anesthesia. Human adipose-derived extracellular matrix (ECM grafts have been reported to form new adipose tissue and have greater biostability than autologous fat graft. Here, we present an injectable hydrogel that is constructed from adipose tissue derived soluble extracellular matrix (sECM and methylcellulose (MC for use in vocal fold augmentation. Human sECM derived from adipose tissue was extracted using two major steps-ECM was isolated from human adipose tissue and was subsequently solubilized. Injectable sECM/MC hydrogels were prepared by blending of sECM and MC. Sustained vocal fold augmentation and symmetric vocal fold vibration were accomplished by the sECM/MC hydrogel in paralyzed vocal fold which were confirmed by laryngoscope, histology and a high-speed imaging system. There were increased number of collagen fibers and fatty granules at the injection site without significant inflammation or fibrosis. Overall, these results indicate that the sECM/MC hydrogel can enhance vocal function in paralyzed vocal folds without early resorption and has potential as a promising material for injection laryngoplasty for stable vocal fold augmentation which can overcome the shortcomings of autologous fat such as unpredictable duration and morbidity associated with the fat harvest.

  6. Effects of a higher dose of near-infrared light on clinical signs and neuroprotection in a monkey model of Parkinson's disease.

    Science.gov (United States)

    Moro, Cécile; El Massri, Nabil; Darlot, Fannie; Torres, Napoleon; Chabrol, Claude; Agay, Diane; Auboiroux, Vincent; Johnstone, Daniel M; Stone, Jonathan; Mitrofanis, John; Benabid, Alim-Louis

    2016-10-01

    We have reported previously that intracranial application of near-infrared light (NIr) - when delivered at the lower doses of 25J and 35J - reduces clinical signs and offers neuroprotection in a subacute MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkey model of Parkinson's disease. In this study, we explored whether a higher NIr dose (125J) generated beneficial effects in the same MPTP monkey model (n=15). We implanted an NIr (670nm) optical fibre device within a midline region of the midbrain in macaque monkeys, close to the substantia nigra of both sides. MPTP injections (1.8-2.1mg/kg) were made over a five day period, during which time the NIr device was turned on and left on continuously throughout the ensuing three week survival period. Monkeys were evaluated clinically and their brains processed for immunohistochemistry and stereology. Our results showed that the higher NIr dose did not have any toxic impact on cells at the midbrain implant site. Further, this NIr dose resulted in a higher number of nigral tyrosine hydroxylase immunoreactive cells when compared to the MPTP group. However, the higher NIr dose monkeys showed little evidence for an increase in mean clinical score, number of nigral Nissl-stained cells and density of striatal tyrosine hydroxylase terminations. In summary, the higher NIr dose of 125J was not as beneficial to MPTP-treated monkeys as compared to the lower doses of 25J and 35J, boding well for strategies of NIr dose delivery and device energy consumption in a future clinical trial. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Positron emission tomographic studies on aromatic L-amino acid decarboxylase activity in vivo for L-dopa and 5-hydroxy-L-tryptophan in the monkey brain

    Energy Technology Data Exchange (ETDEWEB)

    Hartvig, P; Tedroff, J; Lindner, K J; Bjurling, P; Chang, C W; Laangstroem, B [Uppsala Univ. (Sweden); Tsukada, H [Central Research Lab., Hamamatsu Photonics Shizuoka, Osaka (Japan); Watanabe, Y [Dept. of Neuroscience, Osaka Bioscience Inst., Osaka (Japan)

    1993-01-01

    The regional brain kinetics following 5-hydroxy-L-([beta]-11 C)tryptophan and L-([beta]-11 C)DOPA intravenous injection was measured in twelve Rhesus monkeys using positron emission tomography (PET). The radiolabelled compounds were also injected together with various doses of unlabelled 5-hydroxy-L-tryptophan or L-DOPA. The radioactivity accumulated in the striatal region and the rate of increased utilization with time was calculated using a graphical method with back of the brain as a reference region. The rate constants for decarboxylation were 0.0070 [+-] 0.0007 (S. D) and 0.0121 [+-] 0.0010 min[sup -1] for 5-hydroxy-L-([beta]-11 C)tryptophan and L-([beta]-11 C)DOPA, respectively. After concomitant injection with unlabelled 5-hydroxy-L-tryptophan, the rate constant of 5-hydroxy-L-([beta]-11 C)tryptophan decreased dose-dependently and a 50 percent reduction was seen with a dose of about 4 mg/kg of unlabelled compound. A decreased utilization rate of L-([beta]-11 C)DOPA was seen only after simultaneous injection of 30 mg/kg of either L-DOPA or 5-hydroxy-L-tryptophan. This capacity limitation was most likely interpreted as different affinity of the striatal aromatic amino acid decarboxylase for L-DOPA and 5-hydroxy-L-tryptophan, respectively.

  8. Biodistribution of Idursulfase Formulated for Intrathecal Use (Idursulfase-IT in Cynomolgus Monkeys after Intrathecal Lumbar Administration.

    Directory of Open Access Journals (Sweden)

    Jou-Ku Chung

    Full Text Available Enzyme replacement therapy with intravenous idursulfase (recombinant iduronate-2-sulfatase is approved for the treatment of Hunter syndrome. Intravenous administration does not, however, treat the neurological manifestations, due to its low central nervous system bioavailability. Using intrathecal-lumbar administration, iduronate-2-sulfatase is delivered directly to the central nervous system. This study investigates the central nervous system biodistribution of intrathecal-lumbar administered iduronate-2-sulfatase in cynomolgus monkeys. Twelve monkeys were administered iduronate-2-sulfatase in one 30 mg intrathecal-lumbar injection. Brain, spinal cord, liver, and kidneys were collected for iduronate-2-sulfatase concentration (measured by an enzyme linked immunosorbent assay and enzyme activity measurement (via a method utilizing 4-methylumbelliferyl-α-iduronate-2-sulfate at 1, 2, 5, 12, 24, and 48 hours following administration. The tissue enzyme linked immunosorbent assay confirmed iduronate-2-sulfatase uptake to the brain, spinal cord, kidneys, and liver in a time-dependent manner. In spinal cord and brain, iduronate-2-sulfatase appeared as early as 1 hour following administration, and peak concentrations were observed at ~2 and ~5 hours. Iduronate-2-sulfatase appeared in liver and kidneys 1 hour post intrathecal-lumbar dose with peak concentrations between 5 and 24 hours. Liver iduronate-2-sulfatase concentration was approximately 10-fold higher than kidney. The iduronate-2-sulfatase localization and enzyme activity in the central nervous system, following intrathecal administration, demonstrates that intrathecal-lumbar treatment with iduronate-2-sulfatase may be considered for further investigation as a treatment for Hunter syndrome patients with neurocognitive impairment.

  9. Monkey Business

    Science.gov (United States)

    Blackwood, Christine Horvatis

    2012-01-01

    A ballerina, a gladiator, a camper, a baseball player, a surfer, and a shopper; these are just a few of the amazing monkeys that the author's seventh graders created from papier-mache. This project provided an opportunity for students to express themselves through the creation of sculptural characters based on their own interests, hobbies, and…

  10. A Penalized Likelihood Framework For High-Dimensional Phylogenetic Comparative Methods And An Application To New-World Monkeys Brain Evolution.

    Science.gov (United States)

    Julien, Clavel; Leandro, Aristide; Hélène, Morlon

    2018-06-19

    Working with high-dimensional phylogenetic comparative datasets is challenging because likelihood-based multivariate methods suffer from low statistical performances as the number of traits p approaches the number of species n and because some computational complications occur when p exceeds n. Alternative phylogenetic comparative methods have recently been proposed to deal with the large p small n scenario but their use and performances are limited. Here we develop a penalized likelihood framework to deal with high-dimensional comparative datasets. We propose various penalizations and methods for selecting the intensity of the penalties. We apply this general framework to the estimation of parameters (the evolutionary trait covariance matrix and parameters of the evolutionary model) and model comparison for the high-dimensional multivariate Brownian (BM), Early-burst (EB), Ornstein-Uhlenbeck (OU) and Pagel's lambda models. We show using simulations that our penalized likelihood approach dramatically improves the estimation of evolutionary trait covariance matrices and model parameters when p approaches n, and allows for their accurate estimation when p equals or exceeds n. In addition, we show that penalized likelihood models can be efficiently compared using Generalized Information Criterion (GIC). We implement these methods, as well as the related estimation of ancestral states and the computation of phylogenetic PCA in the R package RPANDA and mvMORPH. Finally, we illustrate the utility of the new proposed framework by evaluating evolutionary models fit, analyzing integration patterns, and reconstructing evolutionary trajectories for a high-dimensional 3-D dataset of brain shape in the New World monkeys. We find a clear support for an Early-burst model suggesting an early diversification of brain morphology during the ecological radiation of the clade. Penalized likelihood offers an efficient way to deal with high-dimensional multivariate comparative data.

  11. Suppression of metabolic activity caused by infantile strabismus and strabismic amblyopia in striate visual cortex of macaque monkeys.

    Science.gov (United States)

    Wong, Agnes M F; Burkhalter, Andreas; Tychsen, Lawrence

    2005-02-01

    Suppression is a major sensorial abnormality in humans and monkeys with infantile strabismus. We previously reported evidence of metabolic suppression in the visual cortex of strabismic macaques, using the mitochondrial enzyme cytochrome oxidase as an anatomic label. The purpose of this study was to further elucidate alterations in cortical metabolic activity, with or without amblyopia. Six macaque monkeys were used in the experiments (four strabismic and two control). Three of the strabismic monkeys had naturally occurring, infantile strabismus (two esotropic, one exotropic). The fourth strabismic monkey had infantile microesotropia induced by alternating monocular occlusion in the first months of life. Ocular motor behaviors and visual acuity were tested after infancy in each animal, and development of stereopsis was recorded during infancy in one strabismic and one control monkey. Ocular dominance columns (ODCs) of the striate visual cortex (area V1) were labeled using cytochrome oxidase (CO) histochemistry alone, or CO in conjunction with an anterograde tracer ([H 3 ]proline or WGA-HRP) injected into one eye. Each of the strabismic monkeys showed inequalities of metabolic activity in ODCs of opposite ocularity, visible as rows of lighter CO staining, corresponding to ODCs of lower metabolic activity, alternating with rows of darker CO staining, corresponding to ODCs of higher metabolic activity. In monkeys who had infantile strabismus and unilateral amblyopia, lower metabolic activity was found in (suppressed) ODCs driven by the nondominant eye in each hemisphere. In monkeys who had infantile esotropia and alternating fixation (no amblyopia), metabolic activity was lower in ODCs driven by the ipsilateral eye in each hemisphere. The suppression included a monocular core zone at the center of ODCs and binocular border zones at the boundaries of ODCs. This suppression was not evident in the monocular lamina of the LGN, indicating an intracortical rather than

  12. Nutrient Intake and Digestibility of Cynomolgus Monkey (Macaca fascicularis Fed with High Soluble Carbohydrate Diet: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    DEWI APRI ASTUTI

    2009-12-01

    Full Text Available High carbohydrate as obese diet is not yet available commercially for monkeys. Therefore, this preliminary study was to carry out nutrient intake and digestibility of cynomolgus monkeys (Macaca fascicularis fed with high soluble carbohydrate diet compared to monkey chow. Five adult female macaques (average body weight 2.67 kg were made to consume freshly diet. Commercial monkey chows (contains 3500 cal/g energy and 35% starch were fed to three adult females (average body weight 3.62 kg. Nutrient intakes and digestibility parameters were measured using modified metabolic cages. Result showed that average of protein, fat, starch, and energy intakes in treatment diet were higher than control diet (T-test. Fat intake in the treatment diet was three times higher, while starch and energy intakes were almost two times higher than monkey chow. Digestibility percentage of all nutrients were the same in both diets except for the protein. The study concludes that the freshly prepared high sugar diet was palatable and digestible for the cynomolgus monkeys. Further studies are in progress to develop obese diet high in energy content based on fat and source of starch treatments.

  13. Functional analysis of aldehyde oxidase using expressed chimeric enzyme between monkey and rat.

    Science.gov (United States)

    Itoh, Kunio; Asakawa, Tasuku; Hoshino, Kouichi; Adachi, Mayuko; Fukiya, Kensuke; Watanabe, Nobuaki; Tanaka, Yorihisa

    2009-01-01

    Aldehyde oxidase (AO) is a homodimer with a subunit molecular mass of approximately 150 kDa. Each subunit consists of about 20 kDa 2Fe-2S cluster domain storing reducing equivalents, about 40 kDa flavine adenine dinucleotide (FAD) domain and about 85 kDa molybdenum cofactor (MoCo) domain containing a substrate binding site. In order to clarify the properties of each domain, especially substrate binding domain, chimeric cDNAs were constructed by mutual exchange of 2Fe-2S/FAD and MoCo domains between monkey and rat. Chimeric monkey/rat AO was referred to one with monkey type 2Fe-2S/FAD domains and a rat type MoCo domain. Rat/monkey AO was vice versa. AO-catalyzed 2-oxidation activities of (S)-RS-8359 were measured using the expressed enzyme in Escherichia coli. Substrate inhibition was seen in rat AO and chimeric monkey/rat AO, but not in monkey AO and chimeric rat/monkey AO, suggesting that the phenomenon might be dependent on the natures of MoCo domain of rat. A biphasic Eadie-Hofstee profile was observed in monkey AO and chimeric rat/monkey AO, but not rat AO and chimeric monkey/rat AO, indicating that the biphasic profile might be related to the properties of MoCo domain of monkey. Two-fold greater V(max) values were observed in monkey AO than in chimeric rat/monkey AO, and in chimeric monkey/rat AO than in rat AO, suggesting that monkey has the more effective electron transfer system than rat. Thus, the use of chimeric enzymes revealed that 2Fe-2S/FAD and MoCo domains affect the velocity and the quantitative profiles of AO-catalyzed (S)-RS-8359 2-oxidation, respectively.

  14. Dissociation of active working memory and passive recognition in rhesus monkeys

    OpenAIRE

    Basile, Benjamin M.; Hampton, Robert R.

    2012-01-01

    Active cognitive control of working memory is central in most human memory models, but behavioral evidence for such control in nonhuman primates is absent and neurophysiological evidence, while suggestive, is indirect. We present behavioral evidence that monkey memory for familiar images is under active cognitive control. Concurrent cognitive demands during the memory delay impaired matching-to-sample performance for familiar images in a demand-dependent manner, indicating that maintaining th...

  15. Hepatic folate metabolism in the chronic alcoholic monkey

    International Nuclear Information System (INIS)

    Tamura, T.; Romero, J.J.; Watson, J.E.; Gong, E.J.; Halsted, C.H.

    1981-01-01

    To assess the role of altered hepatic folate metabolism in the pathogenesis of the folate deficiency of chronic alcoholism, the hepatic metabolism of a tracer dose of 3 H-PteGlu was compared in monkeys given 50% of energy as ethanol for 2 years and in control monkeys. Long-term ethanol feeding resulted in mild hepatic injury, with a significant decrease in hepatic folate levels. Chromatographic studies of liver biopsies obtained after the tracer dose indicated that the processes of reduction, methylation, and formylation of reduced folate and the synthesis of polyglutamyl folates were not affected by long-term ethanol feeding. Hepatic tritium levels were significantly decreased in the ethanol-fed group. These studies suggest that the decrease in hepatic folate levels observed after long-term ethanol ingestion is due to a decrease in hepatic folate levels observed after long-term ethanol ingestion is due to a decreased ability to retain folates in the liver, whereas reduction and further metabolism of folates is not affected

  16. Effects of hippocampal lesions on the monkey's ability to learn large sets of object-place associations.

    Science.gov (United States)

    Belcher, Annabelle M; Harrington, Rebecca A; Malkova, Ludise; Mishkin, Mortimer

    2006-01-01

    Earlier studies found that recognition memory for object-place associations was impaired in patients with relatively selective hippocampal damage (Vargha-Khadem et al., Science 1997; 277:376-380), but was unaffected after selective hippocampal lesions in monkeys (Malkova and Mishkin, J Neurosci 2003; 23:1956-1965). A potentially important methodological difference between the two studies is that the patients were required to remember a set of 20 object-place associations for several minutes, whereas the monkeys had to remember only two such associations at a time, and only for a few seconds. To approximate more closely the task given to the patients, we trained monkeys on several successive sets of 10 object-place pairs each, with each set requiring learning across days. Despite the increased associative memory demands, monkeys given hippocampal lesions were unimpaired relative to their unoperated controls, suggesting that differences other than set size and memory duration underlie the different outcomes in the human and animal studies. (c) 2005 Wiley-Liss, Inc.

  17. The bubble-dependent mechanism of FUS-induced blood-brain barrier opening in mice and in monkeys in vivo

    Science.gov (United States)

    Tung, Yao-Sheng; Marquet, Fabrice; Vlachos, Fotios; Feshitan, Jameel A.; Borden, Mark A.; Konofagou, Elisa E.

    2012-10-01

    The blood-brain barrier (BBB) prevents most neurological drugs from traversing from the cerebral microvasculature into the brain parenchyma. Previous studies have shown that the presence of bubbles in an acoustic field temporarily opens the BBB. The BBB opening pressure threshold was previously identified to lie between 0.30 and 0.46 MPa in the case of the smaller bubbles and between 0.15 and 0.30 MPa in the larger bubble case. However, the physical effects responsible for BBB opening remain unknown. In addition, the noninvasive in vivo cavitation detection with mono-dispersed microbubbles has not been studied as of yet. The purpose of this study is to unveil the physical mechanism of the FUS-induced BBB opening with monodispersed microbubbles. Lipid-shelled microbubbles with three different diameters (1-2, 4-5 and 6-8 μm) were manufactured in-house and size-isolated using differential centrifugation. Sixty-seven (n=67) mice were each injected intravenously with bubbles of either 1-2, 4-5 or 6-8 μm in diameter and the concentration of 107 numbers/mL. The right hippocampus of each mouse was then sonicated using focused ultrasound (1.5 MHz frequency; 100 cycles (67 μs) pulse length; 10 Hz pulse repetition frequency; 1 minute sonication duration) while the left hippocampus served as the control. A 10-MHz transducer was used as a passive cavitation detector (PCD) to determine the threshold of inertial cavitation (IC). Each mouse was sonicated at a specific acoustic peak-rarefactional pressure at 0.15, 0.30, 0.45 or 0.60 MPa in order to identify the threshold of BBB opening and IC. T1-weighted MRI was used to verify the BBB opening and spectrograms were generated in order to detect the IC onset and duration. Our results suggest that the BBB opens as a result of nonlinear (harmonic) bubble oscillation when the bubble diameter is similar to the capillary diameter and with inertial cavitation when it is not. The bubble may thus have to be in contact with the capillary

  18. Four stimulants of the central nervous system: effects on short-term memory in young versus aged monkeys.

    Science.gov (United States)

    Bartus, R T

    1979-07-01

    Aged Rhesus monkeys and young control monkeys were tested in a delayed-response procedure to assess the effects of central-nervous-system (CNS) stimulants on short-term memory (STM). Previous research had established that the aged monkeys showed specific impairments of STM in this procedure. Four different CNS stimulants (methylphenidate, magnesium pemoline, a pentylenetetrazole/niacin mixture, and caffeine) were chosen for evaluation on the basis of their relevancy to current geriatric-psychopharmacologic research. Four different doses of each of the four CNS stimulants were given to each monkey, counter-balanced for possible order effects. Methylphenidate and caffeine impaired the performance of both age groups in this non-human primate cognitive task, even at relatively low dose levels. Magnesium pemoline produced fewer adverse effects and some evidence of improving STM in the aged monkeys, although not within the levels of statistical significance. The pentylenetetrazole/niacin mixture produced a three-way interaction involving age, dose and retention interval. This reflected the fact that although no definite effects were noted under the zero-sec control condition, statistically significant age-related deficits did occur in the STM-dependent retention interval as the dose varied. The data demonstrate that, of these four CNS stimulants, none radily improves (and often may impair) performance of tasks requiring STM. Thus the results of this study offer little support for the hypothesis that general CNS stimulation may constitute significant therapy for cognitive impairments associated with advanced age.

  19. Epigenetic mechanism underlying the development of polycystic ovary syndrome (PCOS-like phenotypes in prenatally androgenized rhesus monkeys.

    Directory of Open Access Journals (Sweden)

    Ning Xu

    Full Text Available The pathogenesis of polycystic ovary syndrome (PCOS is poorly understood. PCOS-like phenotypes are produced by prenatal androgenization (PA of female rhesus monkeys. We hypothesize that perturbation of the epigenome, through altered DNA methylation, is one of the mechanisms whereby PA reprograms monkeys to develop PCOS. Infant and adult visceral adipose tissues (VAT harvested from 15 PA and 10 control monkeys were studied. Bisulfite treated samples were subjected to genome-wide CpG methylation analysis, designed to simultaneously measure methylation levels at 27,578 CpG sites. Analysis was carried out using Bayesian Classification with Singular Value Decomposition (BCSVD, testing all probes simultaneously in a single test. Stringent criteria were then applied to filter out invalid probes due to sequence dissimilarities between human probes and monkey DNA, and then mapped to the rhesus genome. This yielded differentially methylated loci between PA and control monkeys, 163 in infant VAT, and 325 in adult VAT (BCSVD P<0.05. Among these two sets of genes, we identified several significant pathways, including the antiproliferative role of TOB in T cell signaling and transforming growth factor-β (TGF-β signaling. Our results suggest PA may modify DNA methylation patterns in both infant and adult VAT. This pilot study suggests that excess fetal androgen exposure in female nonhuman primates may predispose to PCOS via alteration of the epigenome, providing a novel avenue to understand PCOS in humans.

  20. Allergic asthma induced in rhesus monkeys by house dust mite (Dermatophagoides farinae).

    Science.gov (United States)

    Schelegle, E S; Gershwin, L J; Miller, L A; Fanucchi, M V; Van Winkle, L S; Gerriets, J P; Walby, W F; Omlor, A M; Buckpitt, A R; Tarkington, B K; Wong, V J; Joad, J P; Pinkerton, K B; Wu, R; Evans, M J; Hyde, D M; Plopper, C G

    2001-01-01

    To establish whether allergic asthma could be induced experimentally in a nonhuman primate using a common human allergen, three female rhesus monkeys (Macaca mulatta) were sensitized with house dust mite (Dermatophagoides farinae) allergen (HDMA) by subcutaneous injection, followed by four intranasal sensitizations, and exposure to allergen aerosol 3 hours per day, 3 days per week for up to 13 weeks. Before aerosol challenge, all three monkeys skin-tested positive for HDMA. During aerosol challenge with HDMA, sensitized monkeys exhibited cough and rapid shallow breathing and increased airway resistance, which was reversed by albuterol aerosol treatment. Compared to nonsensitized monkeys, there was a fourfold reduction in the dose of histamine aerosol necessary to produce a 150% increase in airway resistance in sensitized monkeys. After aerosol challenge, serum levels of histamine were elevated in sensitized monkeys. Sensitized monkeys exhibited increased levels of HDMA-specific IgE in serum, numbers of eosinophils and exfoliated cells within lavage, and elevated CD25 expression on circulating CD4(+) lymphocytes. Intrapulmonary bronchi of sensitized monkeys had focal mucus cell hyperplasia, interstitial infiltrates of eosinophils, and thickening of the basement membrane zone. We conclude that a model of allergic asthma can be induced in rhesus monkeys using a protocol consisting of subcutaneous injection, intranasal instillation, and aerosol challenge with HDMA.

  1. Implicit and Explicit Learning Mechanisms Meet in Monkey Prefrontal Cortex.

    Science.gov (United States)

    Chafee, Matthew V; Crowe, David A

    2017-10-11

    In this issue, Loonis et al. (2017) provide the first description of unique synchrony patterns differentiating implicit and explicit forms of learning in monkey prefrontal networks. Their results have broad implications for how prefrontal networks integrate the two learning mechanisms to control behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Head Rotation Detection in Marmoset Monkeys

    Science.gov (United States)

    Simhadri, Sravanthi

    Head movement is known to have the benefit of improving the accuracy of sound localization for humans and animals. Marmoset is a small bodied New World monkey species and it has become an emerging model for studying the auditory functions. This thesis aims to detect the horizontal and vertical rotation of head movement in marmoset monkeys. Experiments were conducted in a sound-attenuated acoustic chamber. Head movement of marmoset monkey was studied under various auditory and visual stimulation conditions. With increasing complexity, these conditions are (1) idle, (2) sound-alone, (3) sound and visual signals, and (4) alert signal by opening and closing of the chamber door. All of these conditions were tested with either house light on or off. Infra-red camera with a frame rate of 90 Hz was used to capture of the head movement of monkeys. To assist the signal detection, two circular markers were attached to the top of monkey head. The data analysis used an image-based marker detection scheme. Images were processed using the Computation Vision Toolbox in Matlab. The markers and their positions were detected using blob detection techniques. Based on the frame-by-frame information of marker positions, the angular position, velocity and acceleration were extracted in horizontal and vertical planes. Adaptive Otsu Thresholding, Kalman filtering and bound setting for marker properties were used to overcome a number of challenges encountered during this analysis, such as finding image segmentation threshold, continuously tracking markers during large head movement, and false alarm detection. The results show that the blob detection method together with Kalman filtering yielded better performances than other image based techniques like optical flow and SURF features .The median of the maximal head turn in the horizontal plane was in the range of 20 to 70 degrees and the median of the maximal velocity in horizontal plane was in the range of a few hundreds of degrees per

  3. A specialized face-processing model inspired by the organization of monkey face patches explains several face-specific phenomena observed in humans.

    Science.gov (United States)

    Farzmahdi, Amirhossein; Rajaei, Karim; Ghodrati, Masoud; Ebrahimpour, Reza; Khaligh-Razavi, Seyed-Mahdi

    2016-04-26

    Converging reports indicate that face images are processed through specialized neural networks in the brain -i.e. face patches in monkeys and the fusiform face area (FFA) in humans. These studies were designed to find out how faces are processed in visual system compared to other objects. Yet, the underlying mechanism of face processing is not completely revealed. Here, we show that a hierarchical computational model, inspired by electrophysiological evidence on face processing in primates, is able to generate representational properties similar to those observed in monkey face patches (posterior, middle and anterior patches). Since the most important goal of sensory neuroscience is linking the neural responses with behavioral outputs, we test whether the proposed model, which is designed to account for neural responses in monkey face patches, is also able to predict well-documented behavioral face phenomena observed in humans. We show that the proposed model satisfies several cognitive face effects such as: composite face effect and the idea of canonical face views. Our model provides insights about the underlying computations that transfer visual information from posterior to anterior face patches.

  4. Anti-α4 antibody treatment blocks virus traffic to the brain and gut early, and stabilizes CNS injury late in infection.

    Directory of Open Access Journals (Sweden)

    Jennifer H Campbell

    2014-12-01

    Full Text Available Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab once a week for three weeks beginning on 28 days post-infection (late. Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS, and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+ in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.

  5. Anti-α4 antibody treatment blocks virus traffic to the brain and gut early, and stabilizes CNS injury late in infection.

    Science.gov (United States)

    Campbell, Jennifer H; Ratai, Eva-Maria; Autissier, Patrick; Nolan, David J; Tse, Samantha; Miller, Andrew D; González, R Gilberto; Salemi, Marco; Burdo, Tricia H; Williams, Kenneth C

    2014-12-01

    Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab) once a week for three weeks beginning on 28 days post-infection (late). Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS), and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+) in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early) for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.

  6. Non invasive Brain-Computer Interface system: towards its application as assistive technology

    Science.gov (United States)

    Cincotti, Febo; Mattia, Donatella; Aloise, Fabio; Bufalari, Simona; Schalk, Gerwin; Oriolo, Giuseppe; Cherubini, Andrea; Marciani, Maria Grazia; Babiloni, Fabio

    2010-01-01

    The quality of life of people suffering from severe motor disabilities can benefit from the use of current assistive technology capable of ameliorating communication, house-environment management and mobility, according to the user's residual motor abilities. Brain Computer Interfaces (BCIs) are systems that can translate brain activity into signals that control external devices. Thus they can represent the only technology for severely paralyzed patients to increase or maintain their communication and control options. Here we report on a pilot study in which a system was implemented and validated to allow disabled persons to improve or recover their mobility (directly or by emulation) and communication within the surrounding environment. The system is based on a software controller that offers to the user a communication interface that is matched with the individual's residual motor abilities. Patients (n=14) with severe motor disabilities due to progressive neurodegenerative disorders were trained to use the system prototype under a rehabilitation program carried out in a house-like furnished space. All users utilized regular assistive control options (e.g., microswitches or head trackers). In addition, four subjects learned to operate the system by means of a non-invasive EEG-based BCI. This system was controlled by the subjects' voluntary modulations of EEG sensorimotor rhythms recorded on the scalp; this skill was learnt even though the subjects have not had control over their limbs for a long time. We conclude that such a prototype system, which integrates several different assistive technologies including a BCI system, can potentially facilitate the translation from pre-clinical demonstrations to a clinical useful BCI. PMID:18394526

  7. In vitro incorporation of (U-C/sup 14/)-glucose and (1-C/sup 14/)-sodium acetate in peripheral nerves of malnourished young rhesus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Rana, S V; Mehta, S; Chopra, J S; Nain, C K; Mehta, J; Dhand, U K

    1984-01-01

    The effect of protein calorie malnutrition (PCM) on synthesis of lipids in peripheral nerves was studied by in vitro incorporation of (U-C/sup 14/)-glucose and (1-C/sup 14/)-sodium acetate. Ulnar and tibial nerves obtained from five young rhesus monkeys with PCM, five rehabilitated monkeys, and five control monkeys were incubated for 2 h with the radioactive precursors. Uptake of both radioactive precursors in whole peripheral nerves as well as myelin marker lipids was significantly decreased in animals with PCM. However, uptake returned to normal in rehabilitated monkeys.

  8. A deficit in face-voice integration in developing vervet monkeys exposed to ethanol during gestation.

    Directory of Open Access Journals (Sweden)

    Shahin Zangenehpour

    Full Text Available Children with fetal alcohol spectrum disorders display behavioural and intellectual impairments that strongly implicate dysfunction within the frontal cortex. Deficits in social behaviour and cognition are amongst the most pervasive outcomes of prenatal ethanol exposure. Our naturalistic vervet monkey model of fetal alcohol exposure (FAE provides an unparalleled opportunity to study the neurobehavioral outcomes of prenatal ethanol exposure in a controlled experimental setting. Recent work has revealed a significant reduction of the neuronal population in the frontal lobes of these monkeys. We used an intersensory matching procedure to investigate audiovisual perception of socially relevant stimuli in young FAE vervet monkeys. Here we show a domain-specific deficit in audiovisual integration of socially relevant stimuli. When FAE monkeys were shown a pair of side-by-side videos of a monkey concurrently presenting two different calls along with a single audio track matching the content of one of the calls, they were not able to match the correct video to the single audio track. This was manifest by their average looking time being equally spent towards both the matching and non-matching videos. However, a group of normally developing monkeys exhibited a significant preference for the non-matching video. This inability to integrate and thereby discriminate audiovisual stimuli was confined to the integration of faces and voices as revealed by the monkeys' ability to match a dynamic face to a complex tone or a black-and-white checkerboard to a pure tone, presumably based on duration and/or onset-offset synchrony. Together, these results suggest that prenatal ethanol exposure negatively affects a specific domain of audiovisual integration. This deficit is confined to the integration of information that is presented by the face and the voice and does not affect more elementary aspects of sensory integration.

  9. A deficit in face-voice integration in developing vervet monkeys exposed to ethanol during gestation.

    Science.gov (United States)

    Zangenehpour, Shahin; Javadi, Pasha; Ervin, Frank R; Palmour, Roberta M; Ptito, Maurice

    2014-01-01

    Children with fetal alcohol spectrum disorders display behavioural and intellectual impairments that strongly implicate dysfunction within the frontal cortex. Deficits in social behaviour and cognition are amongst the most pervasive outcomes of prenatal ethanol exposure. Our naturalistic vervet monkey model of fetal alcohol exposure (FAE) provides an unparalleled opportunity to study the neurobehavioral outcomes of prenatal ethanol exposure in a controlled experimental setting. Recent work has revealed a significant reduction of the neuronal population in the frontal lobes of these monkeys. We used an intersensory matching procedure to investigate audiovisual perception of socially relevant stimuli in young FAE vervet monkeys. Here we show a domain-specific deficit in audiovisual integration of socially relevant stimuli. When FAE monkeys were shown a pair of side-by-side videos of a monkey concurrently presenting two different calls along with a single audio track matching the content of one of the calls, they were not able to match the correct video to the single audio track. This was manifest by their average looking time being equally spent towards both the matching and non-matching videos. However, a group of normally developing monkeys exhibited a significant preference for the non-matching video. This inability to integrate and thereby discriminate audiovisual stimuli was confined to the integration of faces and voices as revealed by the monkeys' ability to match a dynamic face to a complex tone or a black-and-white checkerboard to a pure tone, presumably based on duration and/or onset-offset synchrony. Together, these results suggest that prenatal ethanol exposure negatively affects a specific domain of audiovisual integration. This deficit is confined to the integration of information that is presented by the face and the voice and does not affect more elementary aspects of sensory integration.

  10. Sex differences in rhesus monkey toy preferences parallel those of children

    Science.gov (United States)

    Hassett, Janice M.; Siebert, Erin R.; Wallen, Kim

    2008-01-01

    Socialization processes, parents, or peers encouraging play with gender specific toys are thought to be the primary force shaping sex differences in toy preference. A contrast in view is that toy preferences reflect biologically determined preferences for specific activities facilitated by specific toys. Sex differences in juvenile activities, such as rough and tumble play, peer preferences, and infant interest, share similarities in humans and monkeys. Thus if activity preferences shape toy preferences, male and female monkeys may show toy preferences similar to those seen in boys and girls. We compared the interactions of 34 rhesus monkeys, living within a 135 monkey troop, with human wheeled toys and plush toys. Male monkeys, like boys, showed consistent and strong preferences for wheeled toys, while female monkeys, like girls, showed greater variability in preferences. Thus, the magnitude of preference for wheeled over plush toys differed significantly between males and females. The similarities to human findings demonstrate that such preferences can develop without explicit gendered socialization. We offer the hypothesis that toy preferences reflect hormonally influenced behavioral and cognitive biases which are sculpted by social processes into the sex differences seen in monkeys and humans. PMID:18452921

  11. A preliminary report on oral fat tolerance test in rhesus monkeys

    OpenAIRE

    Wu, Di; Liu, Qingsu; Wei, Shiyuan; Zhang, Yu Alex; Yue, Feng

    2014-01-01

    Background Oral fat tolerance test (OFTT) has been widely used to assess the postprandial lipemia in human beings, but there is few studies concerning OFTT in nonhuman primates. This study is designed to explore the feasibility of OFTT in rhesus monkeys. Methods In a cross-over study, a total of 8 adult female rhesus monkeys were fed with normal monkey diet (NND), high sugar high fat diet (HHD), and extremely high fat diet (EHD), respectively. Each monkey consumed NND, HHD and EHD respectivel...

  12. Rhesus monkey lens as an in vitro model for studying oxidative stress

    International Nuclear Information System (INIS)

    Zigler, J.S. Jr.; Lucas, V.A.; Du, X.Y.

    1989-01-01

    Lenses from young rhesus monkeys were incubated in the presence of H 2 O 2 or oxygen radical generating systems to determine their suitability as a model for investigating lenticular oxidative stress. Additionally, direct comparisons were made between the effects found with the monkey lenses and those observed with cultured rat lenses exposed to the same oxidizing systems. As in earlier studies with rat lenses the monkey lenses exhibited impaired ability to actively accumulate from the medium radioactively labelled rubidium and choline following exposure to oxidative stress. Based on the effects of various scavengers of oxygen radicals it appeared that the mechanisms responsible for lens damage were the same for both rat and monkey lenses. However, rat lenses were damaged by lower concentrations of oxidants than were monkey lenses. It was concluded that oxidative stress affects both rat and monkey lenses by similar mechanisms but that lenses from monkeys, and probably other primates, are more resistant to these effects because they have better endogenous antioxidant defenses

  13. Induced Pluripotent Stem Cell-Derived Neural Cells Survive and Mature in the Nonhuman Primate Brain

    Directory of Open Access Journals (Sweden)

    Marina E. Emborg

    2013-03-01

    Full Text Available The generation of induced pluripotent stem cells (iPSCs opens up the possibility for personalized cell therapy. Here, we show that transplanted autologous rhesus monkey iPSC-derived neural progenitors survive for up to 6 months and differentiate into neurons, astrocytes, and myelinating oligodendrocytes in the brains of MPTP-induced hemiparkinsonian rhesus monkeys with a minimal presence of inflammatory cells and reactive glia. This finding represents a significant step toward personalized regenerative therapies.

  14. Validation of an auditory sensory reinforcement paradigm: Campbell's monkeys (Cercopithecus campbelli) do not prefer consonant over dissonant sounds.

    Science.gov (United States)

    Koda, Hiroki; Basile, Muriel; Olivier, Marion; Remeuf, Kevin; Nagumo, Sumiharu; Blois-Heulin, Catherine; Lemasson, Alban

    2013-08-01

    The central position and universality of music in human societies raises the question of its phylogenetic origin. One of the most important properties of music involves harmonic musical intervals, in response to which humans show a spontaneous preference for consonant over dissonant sounds starting from early human infancy. Comparative studies conducted with organisms at different levels of the primate lineage are needed to understand the evolutionary scenario under which this phenomenon emerged. Although previous research found no preference for consonance in a New World monkey species, the question remained opened for Old World monkeys. We used an experimental paradigm based on a sensory reinforcement procedure to test auditory preferences for consonant sounds in Campbell's monkeys (Cercopithecus campbelli campbelli), an Old World monkey species. Although a systematic preference for soft (70 dB) over loud (90 dB) control white noise was found, Campbell's monkeys showed no preference for either consonant or dissonant sounds. The preference for soft white noise validates our noninvasive experimental paradigm, which can be easily reused in any captive facility to test for auditory preferences. This would suggest that human preference for consonant sounds is not systematically shared with New and Old World monkeys. The sensitivity for harmonic musical intervals emerged probably very late in the primate lineage.

  15. Change detection by rhesus monkeys (Macaca mulatta) and pigeons (Columba livia).

    Science.gov (United States)

    Elmore, L Caitlin; Magnotti, John F; Katz, Jeffrey S; Wright, Anthony A

    2012-08-01

    Two monkeys (Macaca mulatta) learned a color change-detection task where two colored circles (selected from a 4-color set) were presented on a 4 × 4 invisible matrix. Following a delay, the correct response was to touch the changed colored circle. The monkeys' learning, color transfer, and delay transfer were compared to a similar experiment with pigeons. Monkeys, like pigeons (Columba livia), showed full transfer to four novel colors, and to delays as long as 6.4 s, suggesting they remembered the colors as opposed to perceptual based attentional capture process that may work at very short delays. The monkeys and pigeons were further tested to compare transfer with other dimensions. Monkeys transferred to shape and location changes, unlike the pigeons, but neither species transferred to size changes. Thus, monkeys were less restricted in their domain to detect change than pigeons, but both species learned the basic task and appear suitable for comparative studies of visual short-term memory. 2012 APA, all rights reserved

  16. Comparison of Object Recognition Behavior in Human and Monkey

    Science.gov (United States)

    Rajalingham, Rishi; Schmidt, Kailyn

    2015-01-01

    Although the rhesus monkey is used widely as an animal model of human visual processing, it is not known whether invariant visual object recognition behavior is quantitatively comparable across monkeys and humans. To address this question, we systematically compared the core object recognition behavior of two monkeys with that of human subjects. To test true object recognition behavior (rather than image matching), we generated several thousand naturalistic synthetic images of 24 basic-level objects with high variation in viewing parameters and image background. Monkeys were trained to perform binary object recognition tasks on a match-to-sample paradigm. Data from 605 human subjects performing the same tasks on Mechanical Turk were aggregated to characterize “pooled human” object recognition behavior, as well as 33 separate Mechanical Turk subjects to characterize individual human subject behavior. Our results show that monkeys learn each new object in a few days, after which they not only match mean human performance but show a pattern of object confusion that is highly correlated with pooled human confusion patterns and is statistically indistinguishable from individual human subjects. Importantly, this shared human and monkey pattern of 3D object confusion is not shared with low-level visual representations (pixels, V1+; models of the retina and primary visual cortex) but is shared with a state-of-the-art computer vision feature representation. Together, these results are consistent with the hypothesis that rhesus monkeys and humans share a common neural shape representation that directly supports object perception. SIGNIFICANCE STATEMENT To date, several mammalian species have shown promise as animal models for studying the neural mechanisms underlying high-level visual processing in humans. In light of this diversity, making tight comparisons between nonhuman and human primates is particularly critical in determining the best use of nonhuman primates to

  17. Brain structural changes in cynomolgus monkeys administered with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: A longitudinal voxel-based morphometry and diffusion tensor imaging study.

    Science.gov (United States)

    Jeong, Hyeonseok S; Lee, Sang-Rae; Kim, Jieun E; Lyoo, In Kyoon; Yoon, Sujung; Namgung, Eun; Chang, Kyu-Tae; Kim, Bom Sahn; Yang, Sejung; Im, Jooyeon J; Jeon, Saerom; Kang, Ilhyang; Ma, Jiyoung; Chung, Yong-An; Lim, Soo Mee

    2018-01-01

    In animal models of Parkinson's disease (PD), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is one of the most widely used agents that damages the nigrostriatal dopaminergic pathway. However, brain structural changes in response to MPTP remain unclear. This study aimed to investigate in vivo longitudinal changes in gray matter (GM) volume and white matter (WM) microstructure in primate models administered with MPTP. In six cynomolgus monkeys, high-resolution magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) scans were acquired 7 times over 32 weeks, and assessments of motor symptoms were conducted over 15 months, before and after the MPTP injection. Changes in GM volume and WM microstructure were estimated on a voxel-by-voxel basis. Mixed-effects regression models were used to examine the trajectories of these structural changes. GM volume initially increased after the MPTP injection and gradually decreased in the striatum, midbrain, and other dopaminergic areas. The cerebellar volume temporarily decreased and returned to its baseline level. The rate of midbrain volume increase was positively correlated with the increase rate of motor symptom severity (Spearman rho = 0.93, p = 0.008). Mean, axial, and radial diffusivity in the striatum and frontal areas demonstrated initial increases and subsequent decreases. The current multi-modal imaging study of MPTP-administered monkeys revealed widespread and dynamic structural changes not only in the nigrostriatal pathway but also in other cortical, subcortical, and cerebellar areas. Our findings may suggest the need to further investigate the roles of inflammatory reactions and glial activation as potential underlying mechanisms of these structural changes.

  18. Emergence of Cryptosporidium hominis Monkey Genotype II and Novel Subtype Family Ik in the Squirrel Monkey (Saimiri sciureus) in China.

    Science.gov (United States)

    Liu, Xuehan; Xie, Na; Li, Wei; Zhou, Ziyao; Zhong, Zhijun; Shen, Liuhong; Cao, Suizhong; Yu, Xingming; Hu, Yanchuan; Chen, Weigang; Peng, Gangneng

    2015-01-01

    A single Cryptosporidium isolate from a squirrel monkey with no clinical symptoms was obtained from a zoo in Ya'an city, China, and was genotyped by PCR amplification and DNA sequencing of the small-subunit ribosomal RNA (SSU rRNA), 70-kDa heat shock protein (HSP70), Cryptosporidium oocyst wall protein, and actin genes. This multilocus genetic characterization determined that the isolate was Cryptosporidium hominis, but carried 2, 10, and 6 nucleotide differences in the SSU rRNA, HSP70, and actin loci, respectively, which is comparable to the variations at these loci between C. hominis and the previously reported monkey genotype (2, 3, and 3 nucleotide differences). Phylogenetic studies, based on neighbor-joining and maximum likelihood methods, showed that the isolate identified in the current study had a distinctly discordant taxonomic status, distinct from known C. hominis and also from the monkey genotype, with respect to the three loci. Restriction fragment length polymorphisms of the SSU rRNA gene obtained from this study were similar to those of known C. hominis but clearly differentiated from the monkey genotype. Further subtyping was performed by sequence analysis of the gene encoding the 60-kDa glycoprotein (gp60). Maximum homology of only 88.3% to C. hominis subtype IdA10G4 was observed for the current isolate, and phylogenetic analysis demonstrated that this particular isolate belonged to a novel C. hominis subtype family, IkA7G4. This study is the first to report C. hominis infection in the squirrel monkey and, based on the observed genetic characteristics, confirms a new C. hominis genotype, monkey genotype II. Thus, these results provide novel insights into genotypic variation in C. hominis.

  19. An independent brain-computer interface using covert non-spatial visual selective attention

    Science.gov (United States)

    Zhang, Dan; Maye, Alexander; Gao, Xiaorong; Hong, Bo; Engel, Andreas K.; Gao, Shangkai

    2010-02-01

    In this paper, a novel independent brain-computer interface (BCI) system based on covert non-spatial visual selective attention of two superimposed illusory surfaces is described. Perception of two superimposed surfaces was induced by two sets of dots with different colors rotating in opposite directions. The surfaces flickered at different frequencies and elicited distinguishable steady-state visual evoked potentials (SSVEPs) over parietal and occipital areas of the brain. By selectively attending to one of the two surfaces, the SSVEP amplitude at the corresponding frequency was enhanced. An online BCI system utilizing the attentional modulation of SSVEP was implemented and a 3-day online training program with healthy subjects was carried out. The study was conducted with Chinese subjects at Tsinghua University, and German subjects at University Medical Center Hamburg-Eppendorf (UKE) using identical stimulation software and equivalent technical setup. A general improvement of control accuracy with training was observed in 8 out of 18 subjects. An averaged online classification accuracy of 72.6 ± 16.1% was achieved on the last training day. The system renders SSVEP-based BCI paradigms possible for paralyzed patients with substantial head or ocular motor impairments by employing covert attention shifts instead of changing gaze direction.

  20. Rhesus monkeys see who they hear: spontaneous cross-modal memory for familiar conspecifics.

    Directory of Open Access Journals (Sweden)

    Ikuma Adachi

    Full Text Available Rhesus monkeys gather much of their knowledge of the social world through visual input and may preferentially represent this knowledge in the visual modality. Recognition of familiar faces is clearly advantageous, and the flexibility and utility of primate social memory would be greatly enhanced if visual memories could be accessed cross-modally either by visual or auditory stimulation. Such cross-modal access to visual memory would facilitate flexible retrieval of the knowledge necessary for adaptive social behavior. We tested whether rhesus monkeys have cross-modal access to visual memory for familiar conspecifics using a delayed matching-to-sample procedure. Monkeys learned visual matching of video clips of familiar individuals to photographs of those individuals, and generalized performance to novel videos. In crossmodal probe trials, coo-calls were played during the memory interval. The calls were either from the monkey just seen in the sample video clip or from a different familiar monkey. Even though the monkeys were trained exclusively in visual matching, the calls influenced choice by causing an increase in the proportion of errors to the picture of the monkey whose voice was heard on incongruent trials. This result demonstrates spontaneous cross-modal recognition. It also shows that viewing videos of familiar monkeys activates naturally formed memories of real monkeys, validating the use of video stimuli in studies of social cognition in monkeys.

  1. Preference transitivity and symbolic representation in capuchin monkeys (Cebus apella.

    Directory of Open Access Journals (Sweden)

    Elsa Addessi

    Full Text Available BACKGROUND: Can non-human animals comprehend and employ symbols? The most convincing empirical evidence comes from language-trained apes, but little is known about this ability in monkeys. Tokens can be regarded as symbols since they are inherently non-valuable objects that acquire an arbitrarily assigned value upon exchange with an experimenter. Recent evidence suggested that capuchin monkeys, which diverged from the human lineage 35 million years ago, can estimate, represent and combine token quantities. A fundamental and open question is whether monkeys can reason about symbols in ways similar to how they reason about real objects. METHODOLOGY/PRINCIPAL FINDINGS: Here we examined this broad question in the context of economic choice behavior. Specifically, we assessed whether, in a symbolic context, capuchins' preferences satisfy transitivity--a fundamental trait of rational decision-making. Given three options A, B and C, transitivity holds true if A > or = B, B > or = C and A > or = C (where > or = indicates preference. In this study, we trained monkeys to exchange three types of tokens for three different foods. We then compared choices monkeys made between different types of tokens with choices monkeys made between the foods. Qualitatively, capuchins' preferences revealed by the way of tokens were similar to those measured with the actual foods. In particular, when choosing between tokens, monkeys displayed strict economic preferences and their choices satisfied transitivity. Quantitatively, however, values measured by the way of tokens differed systematically from those measured with the actual foods. In particular, for any pair of foods, the relative value of the preferred food increased when monkeys chose between the corresponding tokens. CONCLUSIONS/SIGNIFICANCE: These results indicate that indeed capuchins are capable of treating tokens as symbols. However, as they do so, capuchins experience the cognitive burdens imposed by symbolic

  2. Wave aberrations in rhesus monkeys with vision-induced ametropias

    Science.gov (United States)

    Ramamirtham, Ramkumar; Kee, Chea-su; Hung, Li-Fang; Qiao-Grider, Ying; Huang, Juan; Roorda, Austin; Smith, Earl L.

    2007-01-01

    The purpose of this study was to investigate the relationship between refractive errors and high-order aberrations in infant rhesus monkeys. Specifically, we compared the monochromatic wave aberrations measured with a Shack-Hartman wavefront sensor between normal monkeys and monkeys with vision-induced refractive errors. Shortly after birth, both normal monkeys and treated monkeys reared with optically induced defocus or form deprivation showed a decrease in the magnitude of high-order aberrations with age. However, the decrease in aberrations was typically smaller in the treated animals. Thus, at the end of the lens-rearing period, higher than normal amounts of aberrations were observed in treated eyes, both hyperopic and myopic eyes and treated eyes that developed astigmatism, but not spherical ametropias. The total RMS wavefront error increased with the degree of spherical refractive error, but was not correlated with the degree of astigmatism. Both myopic and hyperopic treated eyes showed elevated amounts of coma and trefoil and the degree of trefoil increased with the degree of spherical ametropia. Myopic eyes also exhibited a much higher prevalence of positive spherical aberration than normal or treated hyperopic eyes. Following the onset of unrestricted vision, the amount of high-order aberrations decreased in the treated monkeys that also recovered from the experimentally induced refractive errors. Our results demonstrate that high-order aberrations are influenced by visual experience in young primates and that the increase in high-order aberrations in our treated monkeys appears to be an optical byproduct of the vision-induced alterations in ocular growth that underlie changes in refractive error. The results from our study suggest that the higher amounts of wave aberrations observed in ametropic humans are likely to be a consequence, rather than a cause, of abnormal refractive development. PMID:17825347

  3. Measurement of neuronal activity in a macaque monkey in response to animate images using near-infrared spectroscopy (NIRS

    Directory of Open Access Journals (Sweden)

    Masumi Wakita

    2010-06-01

    Full Text Available Near-infrared spectroscopy (NIRS has been used extensively for functional neuroimaging over the past decade, in part because it is considered a powerful tool for investigating brain function in human infants and young children, for whom other neuroimaging techniques are not suitable. In particular, several studies have measured hemodynamic responses in the occipital region in infants upon exposure to visual stimuli. In the present study, we used a multi-channel NIRS to measure neuronal activity in a macaque monkey who was trained to watch videos showing various circus animals performing acrobatic activities without fixing the head position of the monkey. Cortical activity from the occipital region was measured first by placing a probe comprising a 3x5 array of emitters and detectors (2 x 4 cm on the area (area 17, and the robustness and stability of the results were confirmed across sessions. Cortical responses were then measured from the dorsofrontal region. The oxygenated hemoglobin signals increased in area 9 and decreased in area 8b in response to viewing the videos. The results suggest that these regions are involved in cognitive processing of visually presented stimuli. The monkey showed positive responsiveness to the stimuli from the affective standpoint, but its attentional response to them was an inhibitory one.

  4. Do you see what I see? A comparative investigation of the Delboeuf illusion in humans (Homo sapiens), rhesus monkeys (Macaca mulatta), and capuchin monkeys (Cebus apella).

    Science.gov (United States)

    Parrish, Audrey E; Brosnan, Sarah F; Beran, Michael J

    2015-10-01

    Studying visual illusions is critical to understanding typical visual perception. We investigated whether rhesus monkeys (Macaca mulatta) and capuchin monkeys (Cebus apella) perceived the Delboeuf illusion in a similar manner as human adults (Homo sapiens). To test this, in Experiment 1, we presented monkeys and humans with a relative discrimination task that required subjects to choose the larger of 2 central dots that were sometimes encircled by concentric rings. As predicted, humans demonstrated evidence of the Delboeuf illusion, overestimating central dots when small rings surrounded them and underestimating the size of central dots when large rings surrounded them. However, monkeys did not show evidence of the illusion. To rule out an alternate explanation, in Experiment 2, we presented all species with an absolute classification task that required them to classify a central dot as "small" or "large." We presented a range of ring sizes to determine whether the Delboeuf illusion would occur for any dot-to-ring ratios. Here, we found evidence of the Delboeuf illusion in all 3 species. Humans and monkeys underestimated central dot size to a progressively greater degree with progressively larger rings. The Delboeuf illusion now has been extended to include capuchin monkeys and rhesus monkeys, and through such comparative investigations we can better evaluate hypotheses regarding illusion perception among nonhuman animals. (c) 2015 APA, all rights reserved).

  5. Apolipoprotein A-I metabolism in cynomolgus monkey. Identification and characterization of beta-migrating pools

    International Nuclear Information System (INIS)

    Melchior, G.W.; Castle, C.K.

    1989-01-01

    Fresh plasma from control (C) and hypercholesterolemic (HC) cynomolgus monkeys was analyzed by agarose electrophoresis-immunoblotting with antibody to cynomolgus monkey apolipoprotein (apo) A-I. Two bands were evident on the autoradiogram: an alpha-migrating band (high density lipoprotein) and a beta-migrating band that comigrated exactly with cynomolgus monkey low density lipoprotein (LDL). The presence of beta-migrating apo A-I in the plasma of these monkeys was confirmed by Geon-Pevikon preparative electrophoresis, crossed immunoelectrophoresis, and isotope dilution studies in which radiolabeled apo A-I was found to equilibrate also with alpha- and beta-migrating pools of apo A-I in the plasma. Subfractionation of C and HC plasma by agarose column chromatography (Bio-Gel A-0.5M and A-15M) followed by agarose electrophoresis-immunoblotting indicated that the beta-migrating apo A-I in C was relatively homogeneous and eluted with proteins of Mr approximately 50 kD [apo A-I(50 kD)], whereas two beta-migrating fractions were identified in HC, one that eluted with the 50-kD proteins, and the other that eluted in the LDL Mr range [apo A-I(LDL)]. The apo A-I(LDL) was precipitated by antibody to cynomolgus monkey apo B. The apo A-I(50 kD) accounted for 5 +/- 1% (mean +/- SD) of the plasma apo A-I in C plasma, and 15 +/- 7% in HC plasma. No apo A-I(LDL) was detected in C plasma, but that fraction accounted for 9 +/- 7% of the apo A-I in HC plasma. These data establish the presence of multiple pools of apo A-I in the cynomolgus monkey, which must be taken into consideration in any comprehensive model of apo A-I metabolism in this species

  6. The bilingual brain: Flexibility and control in the human cortex

    Science.gov (United States)

    Buchweitz, Augusto; Prat, Chantel

    2013-12-01

    The goal of the present review is to discuss recent cognitive neuroscientific findings concerning bilingualism. Three interrelated questions about the bilingual brain are addressed: How are multiple languages represented in the brain? how are languages controlled in the brain? and what are the real-world implications of experience with multiple languages? The review is based on neuroimaging research findings about the nature of bilingual processing, namely, how the brain adapts to accommodate multiple languages in the bilingual brain and to control which language should be used, and when. We also address how this adaptation results in differences observed in the general cognition of bilingual individuals. General implications for models of human learning, plasticity, and cognitive control are discussed.

  7. Evaluation of diabetes determinants in woolly monkeys (Lagothrix lagotricha)

    NARCIS (Netherlands)

    Ange-van Heugten, K.D.; Burns, R.; Verstegen, M.W.A.; Jansen, W.L.; Ferket, P.R.; Heugten, E.

    2007-01-01

    Woolly monkeys (Lagothrix lagotricha) are a threatened specie in the wild with limited successful management in captivity due to diagnosed hypertension and suspected diabetic conditions. Six woolly monkeys with known hypertension problems were tested to determine if diabetes mellitus and current

  8. Intention concepts and brain-machine interfacing

    Directory of Open Access Journals (Sweden)

    Franziska eThinnes-Elker

    2012-11-01

    Full Text Available Intentions, including their temporal properties and semantic content, are receiving increased attention, and neuroscientific studies in humans vary with respect to the topography of intention-related neural responses. This may reflect the fact that the kind of intentions investigated in one study may not be exactly the same kind investigated in the other. Fine-grained intention taxonomies developed in the philosophy of mind may be useful to identify the neural correlates of well-defined types of intentions, as well as to disentangle them from other related mental states, such as mere urges to perform an action. Intention-related neural signals may be exploited by brain-machine interfaces (BMIs that are currently being developed to restore speech and motor control in paralyzed subjects. Such BMI devices record the brain activity of the agent, interpret (‘decode’ the agent’s intended action, and send the corresponding execution command to an artificial effector system, e.g., a computer cursor or a robotic arm. In the present paper, we evaluate the potential of intention concepts from philosophy of mind to improve the performance and safety of BMIs based on higher-order, intention-related control signals. To this end, we address the distinction between future-, present-directed, and motor intentions, as well as the organization of intentions in time, specifically to what extent it is sequential or hierarchical. This has consequences as to whether these different types of intentions can be expected to occur simultaneously or not. We further illustrate how it may be useful or even necessary to distinguish types of intentions exposited in philosophy, including yes- vs. no-intentions and oblique vs. direct intentions, to accurately decode the agent’s intentions from neural signals in practical BMI applications.

  9. Intention concepts and brain-machine interfacing.

    Science.gov (United States)

    Thinnes-Elker, Franziska; Iljina, Olga; Apostolides, John Kyle; Kraemer, Felicitas; Schulze-Bonhage, Andreas; Aertsen, Ad; Ball, Tonio

    2012-01-01

    Intentions, including their temporal properties and semantic content, are receiving increased attention, and neuroscientific studies in humans vary with respect to the topography of intention-related neural responses. This may reflect the fact that the kind of intentions investigated in one study may not be exactly the same kind investigated in the other. Fine-grained intention taxonomies developed in the philosophy of mind may be useful to identify the neural correlates of well-defined types of intentions, as well as to disentangle them from other related mental states, such as mere urges to perform an action. Intention-related neural signals may be exploited by brain-machine interfaces (BMIs) that are currently being developed to restore speech and motor control in paralyzed patients. Such BMI devices record the brain activity of the agent, interpret ("decode") the agent's intended action, and send the corresponding execution command to an artificial effector system, e.g., a computer cursor or a robotic arm. In the present paper, we evaluate the potential of intention concepts from philosophy of mind to improve the performance and safety of BMIs based on higher-order, intention-related control signals. To this end, we address the distinction between future-, present-directed, and motor intentions, as well as the organization of intentions in time, specifically to what extent it is sequential or hierarchical. This has consequences as to whether these different types of intentions can be expected to occur simultaneously or not. We further illustrate how it may be useful or even necessary to distinguish types of intentions exposited in philosophy, including yes- vs. no-intentions and oblique vs. direct intentions, to accurately decode the agent's intentions from neural signals in practical BMI applications.

  10. Comparative imaging study on monkeys with hemi-parkinsonism

    International Nuclear Information System (INIS)

    Wang Wei; Yu Xiaoping; Mao Jun; Liu Sheng; Wang Xiaoyi; Peng Guangchun; Wang Ruiwen

    2003-01-01

    Objective: To study the imaging appearance of experimental Parkinson's disease (PD) and to evaluate the different medical imaging exams on PD. Methods: CT, MRI, SPECT (dopamine transporter imaging and regional cerebral blood flow imaging, DAT imaging and rCBF imaging), and PET (glucose metabolism imaging) were performed on 8 monkeys before and after the infusion of MPTP into unilateral internal carotid artery to develop hemi-Parkinsonism models. Results: Hemi-Parkinsonism models were successfully induced on all 8 monkeys. On DAT imaging, the uptake values of the lesioned striatums decreased obviously after the MPTP treatment and were lower than that of the contralateral ones. The glucose metabolic rates of the lesioned striatums and thalamus in PD models were lower, compared to that of the healthy monkeys and that of the contralateral sides of themselves. Neither DAT nor glucose metabolism abnormalities was found on both the contralateral sides of the healthy and PD monkeys. On MRI images before MPTP treatment, only 4 of 8 PD models showed hypointense in bilateral globus pallidus. No abnormal MRI findings occurred in the first 2 months after injection of MPTP. At tile third month, hypointense appeared in globus pallidus of three monkeys. Enlarged hyposignal region in globus pallidus were found in three models. Of the above 6 monkeys, two appeared hypointense in putamina. Substantia nigra demonstrated no abnormalities before and after MPTP treatment. All rCBF and CT images were normal. Conclusion: The decreased density of DAT and decreased glucose metabolism on experimental PD can be showed early by DAT imaging and glucose metabolism imaging, MRI can show abnormal signal in the basal ganglia of PD but it is later than DAT and glucose metabolism imaging. CT and rCBF find no abnormality on PD

  11. Widespread and evolutionary analysis of a MITE family Monkey King in Brassicaceae.

    Science.gov (United States)

    Dai, Shutao; Hou, Jinna; Long, Yan; Wang, Jing; Li, Cong; Xiao, Qinqin; Jiang, Xiaoxue; Zou, Xiaoxiao; Zou, Jun; Meng, Jinling

    2015-06-19

    Miniature inverted repeat transposable elements (MITEs) are important components of eukaryotic genomes, with hundreds of families and many copies, which may play important roles in gene regulation and genome evolution. However, few studies have investigated the molecular mechanisms involved. In our previous study, a Tourist-like MITE, Monkey King, was identified from the promoter region of a flowering time gene, BnFLC.A10, in Brassica napus. Based on this MITE, the characteristics and potential roles on gene regulation of the MITE family were analyzed in Brassicaceae. The characteristics of the Tourist-like MITE family Monkey King in Brassicaceae, including its distribution, copies and insertion sites in the genomes of major Brassicaceae species were analyzed in this study. Monkey King was actively amplified in Brassica after divergence from Arabidopsis, which was indicated by the prompt increase in copy number and by phylogenetic analysis. The genomic variations caused by Monkey King insertions, both intra- and inter-species in Brassica, were traced by PCR amplification. Genomic sequence analysis showed that most complete Monkey King elements are located in gene-rich regions, less than 3kb from genes, in both the B. rapa and A. thaliana genomes. Sixty-seven Brassica expressed sequence tags carrying Monkey King fragments were also identified from the NCBI database. Bisulfite sequencing identified specific DNA methylation of cytosine residues in the Monkey King sequence. A fragment containing putative TATA-box motifs in the MITE sequence could bind with nuclear protein(s) extracted from leaves of B. napus plants. A Monkey King-related microRNA, bna-miR6031, was identified in the microRNA database. In transgenic A. thaliana, when the Monkey King element was inserted upstream of 35S promoter, the promoter activity was weakened. Monkey King, a Brassicaceae Tourist-like MITE family, has amplified relatively recently and has induced intra- and inter-species genomic

  12. In vivo evaluation of alpha7 nicotinic acetylcholine receptor agonists [11C]A-582941 and [11C]A-844606 in mice and conscious monkeys.

    Directory of Open Access Journals (Sweden)

    Jun Toyohara

    Full Text Available BACKGROUND: The alpha7 nicotinic acetylcholine receptors (nAChRs play an important role in the pathophysiology of neuropsychiatric diseases such as schizophrenia and Alzheimer's disease. The goal of this study was to evaluate the two carbon-11-labeled alpha7 nAChR agonists [(11C]A-582941 and [(11C]A-844606 for their potential as novel positron emission tomography (PET tracers. METHODOLOGY/PRINCIPAL FINDINGS: The two tracers were synthesized by methylation of the corresponding desmethyl precursors using [(11C]methyl triflate. Effects of receptor blockade in mice were determined by coinjection of either tracer along with a carrier or an excess amount of a selective alpha7 nAChR agonist (SSR180711. Metabolic stability was investigated using radio-HPLC. Dynamic PET scans were performed in conscious monkeys with/without SSR180711-treatment. [(11C]A-582941 and [(11C]A-844606 showed high uptake in the mouse brain. Most radioactive compounds in the brain were detected as an unchanged form. However, regional selectivity and selective receptor blockade were not clearly observed for either compound in the mouse brain. On the other hand, the total distribution volume of [(11C]A-582941 and [(11C]A-844606 was high in the hippocampus and thalamus but low in the cerebellum in the conscious monkey brain, and reduced by pretreatment with SSR180711. CONCLUSIONS/SIGNIFICANCE: A nonhuman primate study suggests that [(11C]A-582941 and [(11C]A-844606 would be potential PET ligands for imaging alpha7 nAChRs in the human brain.

  13. Selective bilateral amygdala lesions in rhesus monkeys fail to disrupt object reversal learning.

    Science.gov (United States)

    Izquierdo, Alicia; Murray, Elisabeth A

    2007-01-31

    Neuropsychological studies in nonhuman primates have led to the view that the amygdala plays an essential role in stimulus-reward association. The main evidence in support of this idea is that bilateral aspirative or radiofrequency lesions of the amygdala yield severe impairments on object reversal learning, a task that assesses the ability to shift choices of objects based on the presence or absence of food reward (i.e., reward contingency). The behavioral effects of different lesion techniques, however, can vary. The present study therefore evaluated the effects of selective, excitotoxic lesions of the amygdala in rhesus monkeys on object reversal learning. For comparison, we tested the same monkeys on a task known to be sensitive to amygdala damage, the reinforcer devaluation task. Contrary to previous results based on less selective lesion techniques, monkeys with complete excitotoxic amygdala lesions performed object reversal learning as quickly as controls. As predicted, however, the same operated monkeys were impaired in making object choices after devaluation of the associated food reinforcer. The results suggest two conclusions. First, the results demonstrate that the amygdala makes a selective contribution to stimulus-reward association; the amygdala is critical for guiding object choices after changes in reward value but not after changes in reward contingency. Second, the results implicate a critical contribution to object reversal learning of structures nearby the amygdala, perhaps the subjacent rhinal cortex.

  14. Using Diffusion Tractography to Predict Cortical Connection Strength and Distance: A Quantitative Comparison with Tracers in the Monkey

    DEFF Research Database (Denmark)

    Donahue, Chad J.; Sotiropoulos, Stamatios N.; Jbabdi, Saad

    2016-01-01

    of tractography for analyzing interareal corticocortical connectivity in nonhuman primates and a framework for assessing future tractography methodological refinements objectively. SIGNIFICANCE STATEMENT Tractography based on diffusion MRI has great potential for a variety of applications, including estimation......Tractography based on diffusion MRI offers the promise of characterizing many aspects of long-distance connectivity in the brain, but requires quantitative validation to assess its strengths and limitations. Here, we evaluate tractography's ability to estimate the presence and strength...... of connections between areas of macaque neocortex by comparing its results with published data from retrograde tracer injections. Probabilistic tractography was performed on high-quality postmortem diffusion imaging scans from two Old World monkey brains. Tractography connection weights were estimated using...

  15. Glial and neuronal control of brain blood flow

    DEFF Research Database (Denmark)

    Attwell, David; Buchan, Alastair M; Charpak, Serge

    2010-01-01

    Blood flow in the brain is regulated by neurons and astrocytes. Knowledge of how these cells control blood flow is crucial for understanding how neural computation is powered, for interpreting functional imaging scans of brains, and for developing treatments for neurological disorders. It is now...... in our understanding of cerebral blood flow control have important implications for the development of new therapeutic approaches....

  16. Transmission of naturally occurring lymphoma in macaque monkeys.

    OpenAIRE

    Hunt, R D; Blake, B J; Chalifoux, L V; Sehgal, P K; King, N W; Letvin, N L

    1983-01-01

    Spontaneously occurring rhesus monkey lymphomas were transmitted into healthy rhesus monkeys by using tumor cell suspensions. The naturally arising tumors included an immunoblastic sarcoma and an undifferentiated lymphoma. Recipient animals developed undifferentiated lymphomas, poorly differentiated lymphomas, or parenchymal lymphoproliferative abnormalities suggestive of early lesions of lymphoma. Some of these animals developed such opportunistic infections as cytomegalovirus hepatitis and ...

  17. Monkey-based research on human disease: the implications of genetic differences.

    Science.gov (United States)

    Bailey, Jarrod

    2014-11-01

    Assertions that the use of monkeys to investigate human diseases is valid scientifically are frequently based on a reported 90-93% genetic similarity between the species. Critical analyses of the relevance of monkey studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for monkeys to constitute good models for research, and that monkey data do not translate well to progress in clinical practice for humans. Salient examples include the failure of new drugs in clinical trials, the highly different infectivity and pathology of SIV/HIV, and poor extrapolation of research on Alzheimer's disease, Parkinson's disease and stroke. The major molecular differences underlying these inter-species phenotypic disparities have been revealed by comparative genomics and molecular biology - there are key differences in all aspects of gene expression and protein function, from chromosome and chromatin structure to post-translational modification. The collective effects of these differences are striking, extensive and widespread, and they show that the superficial similarity between human and monkey genetic sequences is of little benefit for biomedical research. The extrapolation of biomedical data from monkeys to humans is therefore highly unreliable, and the use of monkeys must be considered of questionable value, particularly given the breadth and potential of alternative methods of enquiry that are currently available to scientists. 2014 FRAME.

  18. Structural changes in chromosomes of peripheral blood lymphocytes in monkeys subjected to long-term daily irradiation

    International Nuclear Information System (INIS)

    Kosichenko, L.P.

    1976-01-01

    During the period that lasted from 4 to 11 years after the cessation of the long-term daily gamma-irradiation the frequency of chromosome rearrangements in peripheral blood lymphocytes of monkeys exceeded the control level. The number of rearrangements did not change significantly with different total irradiation doses (from 826 to 3677r). The main type of structural chromosome rearrangements were symmetrical chromosome exchanges. Abnormal cell clones in peripheral lymphocytes in monkeys irradiated with low doses exhibited no selective advantages during the periods of investigation

  19. Lethal canine distemper virus outbreak in cynomolgus monkeys in Japan in 2008.

    Science.gov (United States)

    Sakai, Kouji; Nagata, Noriyo; Ami, Yasushi; Seki, Fumio; Suzaki, Yuriko; Iwata-Yoshikawa, Naoko; Suzuki, Tadaki; Fukushi, Shuetsu; Mizutani, Tetsuya; Yoshikawa, Tomoki; Otsuki, Noriyuki; Kurane, Ichiro; Komase, Katsuhiro; Yamaguchi, Ryoji; Hasegawa, Hideki; Saijo, Masayuki; Takeda, Makoto; Morikawa, Shigeru

    2013-01-01

    Canine distemper virus (CDV) has recently expanded its host range to nonhuman primates. A large CDV outbreak occurred in rhesus monkeys at a breeding farm in Guangxi Province, China, in 2006, followed by another outbreak in rhesus monkeys at an animal center in Beijing in 2008. In 2008 in Japan, a CDV outbreak also occurred in cynomolgus monkeys imported from China. In that outbreak, 46 monkeys died from severe pneumonia during a quarantine period. A CDV strain (CYN07-dV) was isolated in Vero cells expressing dog signaling lymphocyte activation molecule (SLAM). Phylogenic analysis showed that CYN07-dV was closely related to the recent CDV outbreaks in China, suggesting continuing chains of CDV infection in monkeys. In vitro, CYN07-dV uses macaca SLAM and macaca nectin4 as receptors as efficiently as dog SLAM and dog nectin4, respectively. CYN07-dV showed high virulence in experimentally infected cynomolgus monkeys and excreted progeny viruses in oral fluid and feces. These data revealed that some of the CDV strains, like CYN07-dV, have the potential to cause acute systemic infection in monkeys.

  20. Economic choices reveal probability distortion in macaque monkeys.

    Science.gov (United States)

    Stauffer, William R; Lak, Armin; Bossaerts, Peter; Schultz, Wolfram

    2015-02-18

    Economic choices are largely determined by two principal elements, reward value (utility) and probability. Although nonlinear utility functions have been acknowledged for centuries, nonlinear probability weighting (probability distortion) was only recently recognized as a ubiquitous aspect of real-world choice behavior. Even when outcome probabilities are known and acknowledged, human decision makers often overweight low probability outcomes and underweight high probability outcomes. Whereas recent studies measured utility functions and their corresponding neural correlates in monkeys, it is not known whether monkeys distort probability in a manner similar to humans. Therefore, we investigated economic choices in macaque monkeys for evidence of probability distortion. We trained two monkeys to predict reward from probabilistic gambles with constant outcome values (0.5 ml or nothing). The probability of winning was conveyed using explicit visual cues (sector stimuli). Choices between the gambles revealed that the monkeys used the explicit probability information to make meaningful decisions. Using these cues, we measured probability distortion from choices between the gambles and safe rewards. Parametric modeling of the choices revealed classic probability weighting functions with inverted-S shape. Therefore, the animals overweighted low probability rewards and underweighted high probability rewards. Empirical investigation of the behavior verified that the choices were best explained by a combination of nonlinear value and nonlinear probability distortion. Together, these results suggest that probability distortion may reflect evolutionarily preserved neuronal processing. Copyright © 2015 Stauffer et al.

  1. EEG Negativity in Fixations Used for Gaze-Based Control: Toward Converting Intentions into Actions with an Eye-Brain-Computer Interface

    Science.gov (United States)

    Shishkin, Sergei L.; Nuzhdin, Yuri O.; Svirin, Evgeny P.; Trofimov, Alexander G.; Fedorova, Anastasia A.; Kozyrskiy, Bogdan L.; Velichkovsky, Boris M.

    2016-01-01

    We usually look at an object when we are going to manipulate it. Thus, eye tracking can be used to communicate intended actions. An effective human-machine interface, however, should be able to differentiate intentional and spontaneous eye movements. We report an electroencephalogram (EEG) marker that differentiates gaze fixations used for control from spontaneous fixations involved in visual exploration. Eight healthy participants played a game with their eye movements only. Their gaze-synchronized EEG data (fixation-related potentials, FRPs) were collected during game's control-on and control-off conditions. A slow negative wave with a maximum in the parietooccipital region was present in each participant's averaged FRPs in the control-on conditions and was absent or had much lower amplitude in the control-off condition. This wave was similar but not identical to stimulus-preceding negativity, a slow negative wave that can be observed during feedback expectation. Classification of intentional vs. spontaneous fixations was based on amplitude features from 13 EEG channels using 300 ms length segments free from electrooculogram contamination (200–500 ms relative to the fixation onset). For the first fixations in the fixation triplets required to make moves in the game, classified against control-off data, a committee of greedy classifiers provided 0.90 ± 0.07 specificity and 0.38 ± 0.14 sensitivity. Similar (slightly lower) results were obtained for the shrinkage Linear Discriminate Analysis (LDA) classifier. The second and third fixations in the triplets were classified at lower rate. We expect that, with improved feature sets and classifiers, a hybrid dwell-based Eye-Brain-Computer Interface (EBCI) can be built using the FRP difference between the intended and spontaneous fixations. If this direction of BCI development will be successful, such a multimodal interface may improve the fluency of interaction and can possibly become the basis for a new input device

  2. EEG Negativity in Fixations Used for Gaze-Based Control: Toward Converting Intentions into Actions with an Eye-Brain-Computer Interface

    Directory of Open Access Journals (Sweden)

    Sergei L. Shishkin

    2016-11-01

    Full Text Available We usually look at an object when we are going to manipulate it. Thus, eye tracking can be used to communicate intended actions. An effective human-machine interface, however, should be able to differentiate intentional and spontaneous eye movements. We report an electroencephalogram (EEG marker that differentiates gaze fixations used for control from spontaneous fixations involved in visual exploration. Eight healthy participants played a game with their eye movements only. Their gaze-synchronized EEG data (fixation-related potentials, FRPs were collected during game’s control-on and control-off conditions. A slow negative wave with a maximum in the parietooccipital region was present in each participant’s averaged FRPs in the control-on conditions and was absent or had much lower amplitude in the control-off condition. This wave was similar but not identical to stimulus-preceding negativity, a slow negative wave that can be observed during feedback expectation. Classification of intentional vs. spontaneous fixations was based on amplitude features from 13 EEG channels using 300 ms length segments free from electrooculogram contamination (200..500 ms relative to the fixation onset. For the first fixations in the fixation triplets required to make moves in the game, classified against control-off data, a committee of greedy classifiers provided 0.90 ± 0.07 specificity and 0.38 ± 0.14 sensitivity. Similar (slightly lower results were obtained for the shrinkage LDA classifier. The second and third fixations in the triplets were classified at lower rate. We expect that, with improved feature sets and classifiers, a hybrid dwell-based Eye-Brain-Computer Interface (EBCI can be built using the FRP difference between the intended and spontaneous fixations. If this direction of BCI development will be successful, such a multimodal interface may improve the fluency of interaction and can possibly become the basis for a new input device for

  3. PENGARUH PERSEPSI EKOWISATA TERHADAP TINGKAT KEPUASAN WISATAWAN DI MONKEY FOREST UBUD, BALI

    Directory of Open Access Journals (Sweden)

    Via Reza Efrida

    2017-07-01

    Full Text Available This study aims to investigate (1 the ecotourism perception of tourists visiting Monkey Forest Ubud; (2 the visitor satisfaction level on Monkey Forest Ubud attraction; and (3 the influence of ecotourism perception on visitor satisfaction level at Monkey Forest Ubud. The result of this research carried out descriptive statistic by using an importance-performance analysis (IPA and inferential statistic by using a simple linear regression analysis. The technique of determining sample size is incidental sampling technique by distributing questionnaires to 170 tourists visiting Monkey Forest Ubud. The result showed that tourists which visit Monkey Forest Ubud strongly agree on the implementation of ecotourism concept. On the other hand, the calculation results of concordance rate showed 89.59% which means that the overall tourist is satisfied with the Monkey Forest Ubud attraction. Moreover, based on the hypothesis testing by using t-test statistical significance showed that there is a significant influence of independent variable (perception of ecotourism on the dependent variable (tourist satisfaction.

  4. Induced pluripotent stem cell-derived neural cells survive and mature in the nonhuman primate brain.

    Science.gov (United States)

    Emborg, Marina E; Liu, Yan; Xi, Jiajie; Zhang, Xiaoqing; Yin, Yingnan; Lu, Jianfeng; Joers, Valerie; Swanson, Christine; Holden, James E; Zhang, Su-Chun

    2013-03-28

    The generation of induced pluripotent stem cells (iPSCs) opens up the possibility for personalized cell therapy. Here, we show that transplanted autologous rhesus monkey iPSC-derived neural progenitors survive for up to 6 months and differentiate into neurons, astrocytes, and myelinating oligodendrocytes in the brains of MPTP-induced hemiparkinsonian rhesus monkeys with a minimal presence of inflammatory cells and reactive glia. This finding represents a significant step toward personalized regenerative therapies. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Reference values of clinical chemistry and hematology parameters in rhesus monkeys (Macaca mulatta).

    Science.gov (United States)

    Chen, Younan; Qin, Shengfang; Ding, Yang; Wei, Lingling; Zhang, Jie; Li, Hongxia; Bu, Hong; Lu, Yanrong; Cheng, Jingqiu

    2009-01-01

    Rhesus monkey models are valuable to the studies of human biology. Reference values for clinical chemistry and hematology parameters of rhesus monkeys are required for proper data interpretation. Whole blood was collected from 36 healthy Chinese rhesus monkeys (Macaca mulatta) of either sex, 3 to 5 yr old. Routine chemistry and hematology parameters, and some special coagulation parameters including thromboelastograph and activities of coagulation factors were tested. We presented here the baseline values of clinical chemistry and hematology parameters in normal Chinese rhesus monkeys. These data may provide valuable information for veterinarians and investigators using rhesus monkeys in experimental studies.

  6. Species differences in [11C]clorgyline binding in brain

    International Nuclear Information System (INIS)

    Fowler, Joanna S.; Ding, Yu-Shin; Logan, Jean; MacGregor, Robert R.; Shea, Colleen; Garza, Victor; Gimi, Raomond; Volkow, Nora D.; Wang, Gene-Jack; Schlyer, David; Ferrieri, Richard; Gatley, S. John; Alexoff, David; Carter, Pauline; King, Payton; Pappas, Naomi; Arnett, Carroll D.

    2001-01-01

    [ 11 C]Clorgyline selectively binds to MAO A in the human brain. This contrasts with a recent report that [ 11 C]clorgyline (in contrast to other labeled MAO A inhibitors) is not retained in the rhesus monkey brain . To explore this difference, we compared [ 11 C]clorgyline in the baboon brain before and after clorgyline pretreatment and we also synthesized deuterium substituted [ 11 C]clorgyline (and its nor-precursor) for comparison. [ 11 C]Clorgyline was not retained in the baboon brain nor was it influenced by clorgyline pretreatment or by deuterium substitution, contrasting to results in humans. This suggests a species difference in the susceptibility of MAO A to inhibition by clorgyline and represents an unusual example of where the behavior of a radiotracer in the baboon brain does not predict its behavior in the human brain

  7. Campbell's monkeys concatenate vocalizations into context-specific call sequences

    Science.gov (United States)

    Ouattara, Karim; Lemasson, Alban; Zuberbühler, Klaus

    2009-01-01

    Primate vocal behavior is often considered irrelevant in modeling human language evolution, mainly because of the caller's limited vocal control and apparent lack of intentional signaling. Here, we present the results of a long-term study on Campbell's monkeys, which has revealed an unrivaled degree of vocal complexity. Adult males produced six different loud call types, which they combined into various sequences in highly context-specific ways. We found stereotyped sequences that were strongly associated with cohesion and travel, falling trees, neighboring groups, nonpredatory animals, unspecific predatory threat, and specific predator classes. Within the responses to predators, we found that crowned eagles triggered four and leopards three different sequences, depending on how the caller learned about their presence. Callers followed a number of principles when concatenating sequences, such as nonrandom transition probabilities of call types, addition of specific calls into an existing sequence to form a different one, or recombination of two sequences to form a third one. We conclude that these primates have overcome some of the constraints of limited vocal control by combinatorial organization. As the different sequences were so tightly linked to specific external events, the Campbell's monkey call system may be the most complex example of ‘proto-syntax’ in animal communication known to date. PMID:20007377

  8. Modified and fuzzified general problem solver for the 'monkey and banana' problem, 1

    International Nuclear Information System (INIS)

    Sano, Norihide; Takahashi, Ryoichi.

    1991-01-01

    The master-and-slave control system should be extensively implemented for the in-service inspection of operating nuclear power stations or the decommission of retired plants. The performance of this system depends on the intelligent slave. In this paper the degree of intelligence is approximated by the given amount of prior knowledge or suggestions. This paper aims at improving the general problem solver (GPS) by incorporating the learning process in order to solve the puzzle of the 'monkey and banana'. The monkey in this puzzle may be a reasonable alternative to represent the intelligent slave. Also, this paper deals with fuzzified problem solving since the master's command is not always crisp to the slave. (author)

  9. Brain structural changes in cynomolgus monkeys administered with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: A longitudinal voxel-based morphometry and diffusion tensor imaging study.

    Directory of Open Access Journals (Sweden)

    Hyeonseok S Jeong

    Full Text Available In animal models of Parkinson's disease (PD, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP is one of the most widely used agents that damages the nigrostriatal dopaminergic pathway. However, brain structural changes in response to MPTP remain unclear. This study aimed to investigate in vivo longitudinal changes in gray matter (GM volume and white matter (WM microstructure in primate models administered with MPTP. In six cynomolgus monkeys, high-resolution magnetic resonance imaging (MRI and diffusion tensor imaging (DTI scans were acquired 7 times over 32 weeks, and assessments of motor symptoms were conducted over 15 months, before and after the MPTP injection. Changes in GM volume and WM microstructure were estimated on a voxel-by-voxel basis. Mixed-effects regression models were used to examine the trajectories of these structural changes. GM volume initially increased after the MPTP injection and gradually decreased in the striatum, midbrain, and other dopaminergic areas. The cerebellar volume temporarily decreased and returned to its baseline level. The rate of midbrain volume increase was positively correlated with the increase rate of motor symptom severity (Spearman rho = 0.93, p = 0.008. Mean, axial, and radial diffusivity in the striatum and frontal areas demonstrated initial increases and subsequent decreases. The current multi-modal imaging study of MPTP-administered monkeys revealed widespread and dynamic structural changes not only in the nigrostriatal pathway but also in other cortical, subcortical, and cerebellar areas. Our findings may suggest the need to further investigate the roles of inflammatory reactions and glial activation as potential underlying mechanisms of these structural changes.

  10. Macaque monkeys can learn token values from human models through vicarious reward.

    Science.gov (United States)

    Bevacqua, Sara; Cerasti, Erika; Falcone, Rossella; Cervelloni, Milena; Brunamonti, Emiliano; Ferraina, Stefano; Genovesio, Aldo

    2013-01-01

    Monkeys can learn the symbolic meaning of tokens, and exchange them to get a reward. Monkeys can also learn the symbolic value of a token by observing conspecifics but it is not clear if they can learn passively by observing other actors, e.g., humans. To answer this question, we tested two monkeys in a token exchange paradigm in three experiments. Monkeys learned token values through observation of human models exchanging them. We used, after a phase of object familiarization, different sets of tokens. One token of each set was rewarded with a bit of apple. Other tokens had zero value (neutral tokens). Each token was presented only in one set. During the observation phase, monkeys watched the human model exchange tokens and watched them consume rewards (vicarious rewards). In the test phase, the monkeys were asked to exchange one of the tokens for food reward. Sets of three tokens were used in the first experiment and sets of two tokens were used in the second and third experiments. The valuable token was presented with different probabilities in the observation phase during the first and second experiments in which the monkeys exchanged the valuable token more frequently than any of the neutral tokens. The third experiments examined the effect of unequal probabilities. Our results support the view that monkeys can learn from non-conspecific actors through vicarious reward, even a symbolic task like the token-exchange task.

  11. When "altering brain function" becomes "mind control".

    Science.gov (United States)

    Koivuniemi, Andrew; Otto, Kevin

    2014-01-01

    Functional neurosurgery has seen a resurgence of interest in surgical treatments for psychiatric illness. Deep brain stimulation (DBS) technology is the preferred tool in the current wave of clinical experiments because it allows clinicians to directly alter the functions of targeted brain regions, in a reversible manner, with the intent of correcting diseases of the mind, such as depression, addiction, anorexia nervosa, dementia, and obsessive compulsive disorder. These promising treatments raise a critical philosophical and humanitarian question. "Under what conditions does 'altering brain function' qualify as 'mind control'?" In order to answer this question one needs a definition of mind control. To this end, we reviewed the relevant philosophical, ethical, and neurosurgical literature in order to create a set of criteria for what constitutes mind control in the context of DBS. We also outline clinical implications of these criteria. Finally, we demonstrate the relevance of the proposed criteria by focusing especially on serendipitous treatments involving DBS, i.e., cases in which an unintended therapeutic benefit occurred. These cases highlight the importance of gaining the consent of the subject for the new therapy in order to avoid committing an act of mind control.

  12. Paralyzed by desire: a new type of body integrity identity disorder.

    Science.gov (United States)

    Giummarra, Melita J; Bradshaw, John L; Hilti, Leonie M; Nicholls, Michael E R; Brugger, Peter

    2012-03-01

    Body incongruity in body integrity identity disorder (BIID) manifests in the desire to have a healthy limb amputated. We describe a variant of the disorder: the desire to become paralyzed (paralysis-BIID). Sixteen otherwise healthy participants, recruited through Internet-based forums, websites, or word of mouth, completed questionnaires about details of their desire and accompanying symptoms. Onset of the desire for paralysis typically preceded puberty. All participants indicated a specific level for desired spinal cord injury. All participants simulated paralysis through mental imagery or physical pretending, and 9 (56%) reported erotic interest in paraplegia and/or disability. Our key new finding was that 37.5% of paralysis-BIID participants were women, compared with 4.4% women in a sample of 68 individuals with amputation-BIID. BIID reflects a disunity between self and body, usually with a prominent sexual component. Sex-related differences are emerging: unlike men, a higher proportion of women desire paralysis than desire amputation, and, while men typically seek unilateral amputation, women typically seek bilateral amputation. We propose that these sex-related differences in BIID manifestation may relate to sex differences in cerebral lateralization, or to disruption of representation and/or processing of body-related information in right-hemisphere frontoparietal networks.

  13. Socialization of adult owl monkeys (Aotus sp.) in Captivity.

    Science.gov (United States)

    Williams, Lawrence E; Coke, C S; Weed, J L

    2017-01-01

    Social housing has often been recommended as one-way to address the psychological well-being of captive non-human primates. Published reports have examined methods to socialize compatible animals by forming pairs or groups. Successful socialization rates vary depending on the species, gender, and environment. This study presents a retrospective look at pairing attempts in two species of owl monkeys, Aotus nancymaae and A. azarae, which live in monogamous pairs in the wild. The results of 477 pairing attempt conducted with captive, laboratory housed owl monkeys and 61 hr of behavioral observations are reported here. The greatest success pairing these owl monkeys occurred with opposite sex pairs, with an 82% success rate. Opposite sex pairs were more successful when females were older than males. Female-female pairs were more successful than male-male (MM) pairs (62% vs 40%). Successful pairs stayed together between 3 and 7 years before the animals were separated due to social incompatibility. Vigilance, eating, and sleeping during introductions significantly predicted success, as did the performance of the same behavior in both animals. The results of this analysis show that it is possible to give captive owl monkeys a social alternative even if species appropriate social partners (i.e., opposite sex partners) are not available. The focus of this report is a description of one potential way to enhance the welfare of a specific new world primate, the owl monkey, under laboratory conditions. More important is how the species typical social structure of owl monkeys in nature affects the captive management of this genus. Am. J. Primatol. 79:e22521, 2017. © 2015 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Long term lung clearance and cellular retention of cadmium in rats and monkeys

    International Nuclear Information System (INIS)

    Oberdorster, G.; Cox, C.; Baggs, R.

    1987-01-01

    The paper describes experiments to determine the long term lung clearance and cellular retention of cadmium in rats and monkeys. The rats and monkeys were exposed to 109 Cd Cl 2 aerosols, and one monkey was exposed to 115 CdO particles. The thoracic activity of the respective Cd isotopes was measured with time after exposure, for both species. Accumulation of 109 Cd in the kidneys of the monkeys exposed to 109 Cd Cl 2 was also examined, and autoradiographs of lung sections of these monkeys were also prepared. The results showed that the cadmium accumulated differently in the lungs of the rats and primates. (U.K.)

  15. Effects of prenatal 60Co irradiation on postnatal neural, learning, and hormonal development of the squirrel monkey

    International Nuclear Information System (INIS)

    Ordy, J.M.; Brizzee, K.R.; Dunlap, W.P.; Knight, C.

    1982-01-01

    The goals of this study were to examine the effects of 0, 50, and 100 rad of 60 Co administered prenatally on postnatal development of neuromuscular coordination, visual discrimination learning, spontaneous light-dark stabilimeter activity, plasma cortisol, and somatometric growth rates of diurnal squirrel monkeys from birth to 90 days. In terms of accuracy, completeness, and time required for performance of reflexes and neuromuscular coordination, the performance of 50- and 100-rad offspring was less accurate and poorly coordinated and required more time for completion to that of controls. In visual orientation, discrimination, and reversal learning, the percentage correct responses of the 50- and 100-rad offspring were significantly lower than those of controls. Spontaneous light-dark stabilimeter activity of 50- and 100-rad offspring was significantly higher in the dark session than that of controls. Plasma cortisol was significantly higher in 100-rad infants than in controls. Comparisons of somatometric growth rates indicated that postnatal head circumference, crown-rump length, and to a lesser extent body weight increased at significantly slower rates in 50- and 100-rad offspring. These findings should provide essential information for formulating and carrying out multivariate behavioral, biochemical, and morphometric assessments of low-dose effects on the brain of primate offspring within demonstrable dose-response curves

  16. Perceptual Learning: 12-Month-Olds' Discrimination of Monkey Faces

    Science.gov (United States)

    Fair, Joseph; Flom, Ross; Jones, Jacob; Martin, Justin

    2012-01-01

    Six-month-olds reliably discriminate different monkey and human faces whereas 9-month-olds only discriminate different human faces. It is often falsely assumed that perceptual narrowing reflects a permanent change in perceptual abilities. In 3 experiments, ninety-six 12-month-olds' discrimination of unfamiliar monkey faces was examined. Following…

  17. Glial and neuronal control of brain blood flow

    DEFF Research Database (Denmark)

    Attwell, David; Buchan, Alastair M; Charpak, Serge

    2010-01-01

    Blood flow in the brain is regulated by neurons and astrocytes. Knowledge of how these cells control blood flow is crucial for understanding how neural computation is powered, for interpreting functional imaging scans of brains, and for developing treatments for neurological disorders. It is now...... recognized that neurotransmitter-mediated signalling has a key role in regulating cerebral blood flow, that much of this control is mediated by astrocytes, that oxygen modulates blood flow regulation, and that blood flow may be controlled by capillaries as well as by arterioles. These conceptual shifts...

  18. Basic math in monkeys and college students.

    Science.gov (United States)

    Cantlon, Jessica F; Brannon, Elizabeth M

    2007-12-01

    Adult humans possess a sophisticated repertoire of mathematical faculties. Many of these capacities are rooted in symbolic language and are therefore unlikely to be shared with nonhuman animals. However, a subset of these skills is shared with other animals, and this set is considered a cognitive vestige of our common evolutionary history. Current evidence indicates that humans and nonhuman animals share a core set of abilities for representing and comparing approximate numerosities nonverbally; however, it remains unclear whether nonhuman animals can perform approximate mental arithmetic. Here we show that monkeys can mentally add the numerical values of two sets of objects and choose a visual array that roughly corresponds to the arithmetic sum of these two sets. Furthermore, monkeys' performance during these calculations adheres to the same pattern as humans tested on the same nonverbal addition task. Our data demonstrate that nonverbal arithmetic is not unique to humans but is instead part of an evolutionarily primitive system for mathematical thinking shared by monkeys.

  19. Delayed response task performance as a function of age in cynomolgus monkeys (Macaca fascicularis)

    DEFF Research Database (Denmark)

    Darusman, H S; Call, J; Sajuthi, D

    2014-01-01

    We compared delayed response task performance in young, middle-aged, and old cynomolgus monkeys using three memory tests that have been used with non-human primates. Eighteen cynomolgus monkeys-6 young (4-9 years), 6 middle-aged (10-19 years), and 6 old (above 20 years)-were tested. In general......, the old monkeys scored significantly worse than did the animals in the two other age groups. Longer delays between stimulus presentation and response increased the performance differences between the old and younger monkeys. The old monkeys in particular showed signs of impaired visuo-spatial memory...

  20. In vivo evaluation of carbon-11-labelled non-sarcosine-based glycine transporter 1 inhibitors in mice and conscious monkeys

    International Nuclear Information System (INIS)

    Toyohara, Jun; Ishiwata, Kiichi; Sakata, Muneyuki; Wu, Jin; Nishiyama, Shingo; Tsukada, Hideo; Hashimoto, Kenji

    2011-01-01

    Introduction: Glycine transporter 1 (GlyT-1) is an attractive target in positron emission tomography (PET) studies. Here, we report the in vivo evaluation of three carbon-11-labelled non-sarcosine-type GlyT-1 inhibitors - [ 11 C]SA1, [ 11 C]SA2 and [ 11 C]SA3 - as novel PET tracers for GlyT-1. Methods: The regional brain distributions of the three compounds in mice were studied at baseline and under receptor-blockade conditions with co-injection of carrier loading or pretreatment with an excess of selective GlyT-1 inhibitors (ALX-5407 and SSR504734). Metabolic stability was investigated by radio high-performance liquid chromatography. Dynamic PET scans in conscious monkeys were performed with/without selective GlyT-1 inhibitors. Results: The IC 50 values of SA1, SA2 and SA3 were 9.0, 6400 and 39.7 nM, respectively. The regional brain uptakes of [ 11 C]SA1 and [ 11 C]SA3 in mice were heterogeneous and consistent with the known distribution of GlyT-1. [ 11 C]SA2 showed low and homogeneous uptake in the brain. Most radioactivity in the brain was detected in unchanged form, although peripherally these compounds were degraded. Carrier loading decreased the uptake of [ 11 C]SA1 in GlyT-1-rich regions. However, similar reductions were not observed with [ 11 C]SA3. Pretreatment with ALX-5407 decreased the uptake of [ 11 C]SA1 in GlyT-1-rich regions. In the monkey at baseline, regional brain uptake of [ 11 C]SA1 was heterogeneous and consistent with the known GlyT-1 distribution. Pretreatment with selective GlyT-1 inhibitors significantly decreased the distribution volume ratio of [ 11 C] SA1 in GlyT-1-rich regions. Conclusions: [ 11 C]SA1 has the most suitable profile among the three carbon-11-labelled GlyT-1 inhibitors. Lead optimization of [ 11 C]SA1 structure will be required to achieve in vivo selective GlyT-1 imaging.

  1. Finger pressure adjustments to various object configurations during precision grip in humans and monkeys.

    Science.gov (United States)

    Viaro, Riccardo; Tia, Banty; Coudé, Gino; Canto, Rosario; Oliynyk, Andriy; Salmas, Paola; Masia, Lorenzo; Sandini, Giulio; Fadiga, Luciano

    2017-06-01

    In this study, we recorded the pressure exerted onto an object by the index finger and the thumb of the preferred hand of 18 human subjects and either hand of two macaque monkeys during a precision grasping task. The to-be-grasped object was a custom-made device composed by two plates which could be variably oriented by a motorized system while keeping constant the size and thus grip dimension. The to-be-grasped plates were covered by an array of capacitive sensors to measure specific features of finger adaptation, namely pressure intensity and centroid location and displacement. Kinematic measurements demonstrated that for human subjects and for monkeys, different plate configurations did not affect wrist velocity and grip aperture during the reaching phase. Consistently, at the instant of fingers-plates contact, pressure centroids were clustered around the same point for all handle configurations. However, small pressure centroid displacements were specifically adopted for each configuration, indicating that both humans and monkeys can display finger adaptation during precision grip. Moreover, humans applied stronger thumb pressure intensity, performed less centroid displacement and required reduced adjustment time, as compared to monkeys. These pressure patterns remain similar when different load forces were required to pull the handle, as ascertained by additional measurements in humans. The present findings indicate that, although humans and monkeys share common features in motor control of grasping, they differ in the adjustment of fingertip pressure, probably because of skill and/or morphology divergences. Such a precision grip device may form the groundwork for future studies on prehension mechanisms. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  2. High-frequency oscillations in human and monkey neocortex during the wake-sleep cycle.

    Science.gov (United States)

    Le Van Quyen, Michel; Muller, Lyle E; Telenczuk, Bartosz; Halgren, Eric; Cash, Sydney; Hatsopoulos, Nicholas G; Dehghani, Nima; Destexhe, Alain

    2016-08-16

    Beta (β)- and gamma (γ)-oscillations are present in different cortical areas and are thought to be inhibition-driven, but it is not known if these properties also apply to γ-oscillations in humans. Here, we analyze such oscillations in high-density microelectrode array recordings in human and monkey during the wake-sleep cycle. In these recordings, units were classified as excitatory and inhibitory cells. We find that γ-oscillations in human and β-oscillations in monkey are characterized by a strong implication of inhibitory neurons, both in terms of their firing rate and their phasic firing with the oscillation cycle. The β- and γ-waves systematically propagate across the array, with similar velocities, during both wake and sleep. However, only in slow-wave sleep (SWS) β- and γ-oscillations are associated with highly coherent and functional interactions across several millimeters of the neocortex. This interaction is specifically pronounced between inhibitory cells. These results suggest that inhibitory cells are dominantly involved in the genesis of β- and γ-oscillations, as well as in the organization of their large-scale coherence in the awake and sleeping brain. The highest oscillation coherence found during SWS suggests that fast oscillations implement a highly coherent reactivation of wake patterns that may support memory consolidation during SWS.

  3. High-frequency oscillations in human and monkey neocortex during the wake–sleep cycle

    Science.gov (United States)

    Le Van Quyen, Michel; Muller, Lyle E.; Telenczuk, Bartosz; Halgren, Eric; Cash, Sydney; Hatsopoulos, Nicholas G.; Dehghani, Nima; Destexhe, Alain

    2016-01-01

    Beta (β)- and gamma (γ)-oscillations are present in different cortical areas and are thought to be inhibition-driven, but it is not known if these properties also apply to γ-oscillations in humans. Here, we analyze such oscillations in high-density microelectrode array recordings in human and monkey during the wake–sleep cycle. In these recordings, units were classified as excitatory and inhibitory cells. We find that γ-oscillations in human and β-oscillations in monkey are characterized by a strong implication of inhibitory neurons, both in terms of their firing rate and their phasic firing with the oscillation cycle. The β- and γ-waves systematically propagate across the array, with similar velocities, during both wake and sleep. However, only in slow-wave sleep (SWS) β- and γ-oscillations are associated with highly coherent and functional interactions across several millimeters of the neocortex. This interaction is specifically pronounced between inhibitory cells. These results suggest that inhibitory cells are dominantly involved in the genesis of β- and γ-oscillations, as well as in the organization of their large-scale coherence in the awake and sleeping brain. The highest oscillation coherence found during SWS suggests that fast oscillations implement a highly coherent reactivation of wake patterns that may support memory consolidation during SWS. PMID:27482084

  4. Analysis of neural activity in human motor cortex -- Towards brain machine interface system

    Science.gov (United States)

    Secundo, Lavi

    The discovery of directional tuned neurons in the primary motor cortex has advanced motor research in several domains. For instance, in the area of brain machine interface (BMI), researchers have exploited the robust characteristic of tuned motor neurons to allow monkeys to learn control of various machines. In the first chapter of this work we examine whether this phenomena can be observed using the less invasive method of recording electrocorticographic signals (ECoG) from the surface of a human's brain. Our findings reveal that individual ECoG channels contain complex movement information about the neuronal population. While some ECoG channels are tuned to hand movement direction (direction specific channels), others are associated to movement but do not contain information regarding movement direction (non-direction specific channels). More specifically, directionality can vary temporally and by frequency within one channel. In addition, a handful of channels contain no significant information regarding movement at all. These findings strongly suggest that directional and non-directional regions of cortex can be identified with ECoG and provide solutions to decoding movement at the signal resolution provided by ECoG. In the second chapter we examine the influence of movement context on movement reconstruction accuracy. We recorded neuronal signals recorded from electro-corticography (ECoG) during performance of cued- and self-initiated movements. ECoG signals were used to train a reconstruction algorithm to reconstruct continuous hand movement. We found that both cued- and self-initiated movements could be reconstructed with similar accuracy from the ECoG data. However, while an algorithm trained on the cued task could reconstruct performance on a subsequent cued trial, it failed to reconstruct self-initiated arm movement. The same task-specificity was observed when the algorithm was trained with self-initiated movement data and tested on the cued task. Thus

  5. Anti-α4 Antibody Treatment Blocks Virus Traffic to the Brain and Gut Early, and Stabilizes CNS Injury Late in Infection

    OpenAIRE

    Campbell, Jennifer H.; Ratai, Eva-Maria; Autissier, Patrick; Nolan, David J.; Tse, Samantha; Miller, Andrew D.; González, R. Gilberto; Salemi, Marco; Burdo, Tricia H.; Williams, Kenneth C.

    2014-01-01

    Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab) once a week for three weeks beginning on 28 days post-infection (late). Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS), and decreased numbers of monocytes/macrophages a...

  6. Design and validation of a real-time spiking-neural-network decoder for brain-machine interfaces

    Science.gov (United States)

    Dethier, Julie; Nuyujukian, Paul; Ryu, Stephen I.; Shenoy, Krishna V.; Boahen, Kwabena

    2013-06-01

    Objective. Cortically-controlled motor prostheses aim to restore functions lost to neurological disease and injury. Several proof of concept demonstrations have shown encouraging results, but barriers to clinical translation still remain. In particular, intracortical prostheses must satisfy stringent power dissipation constraints so as not to damage cortex. Approach. One possible solution is to use ultra-low power neuromorphic chips to decode neural signals for these intracortical implants. The first step is to explore in simulation the feasibility of translating decoding algorithms for brain-machine interface (BMI) applications into spiking neural networks (SNNs). Main results. Here we demonstrate the validity of the approach by implementing an existing Kalman-filter-based decoder in a simulated SNN using the Neural Engineering Framework (NEF), a general method for mapping control algorithms onto SNNs. To measure this system’s robustness and generalization, we tested it online in closed-loop BMI experiments with two rhesus monkeys. Across both monkeys, a Kalman filter implemented using a 2000-neuron SNN has comparable performance to that of a Kalman filter implemented using standard floating point techniques. Significance. These results demonstrate the tractability of SNN implementations of statistical signal processing algorithms on different monkeys and for several tasks, suggesting that a SNN decoder, implemented on a neuromorphic chip, may be a feasible computational platform for low-power fully-implanted prostheses. The validation of this closed-loop decoder system and the demonstration of its robustness and generalization hold promise for SNN implementations on an ultra-low power neuromorphic chip using the NEF.

  7. Molecular characterization of Blastocystis isolates from children and rhesus monkeys in Kathmandu, Nepal.

    Science.gov (United States)

    Yoshikawa, Hisao; Wu, Zhiliang; Pandey, Kishor; Pandey, Basu Dev; Sherchand, Jeevan Bahadur; Yanagi, Tetsuo; Kanbara, Hiroji

    2009-03-23

    To investigate the possible transmission of Blastocystis organisms between local rhesus monkeys and children in Kathmandu, Nepal, we compared the subtype (ST) and sequence of Blastocystis isolates from children with gastrointestinal symptoms and local rhesus monkeys. Twenty and 10 Blastocystis isolates were established from 82 and 10 fecal samples obtained from children and monkeys, respectively. Subtype analysis with seven sequence-tagged site (STS) primers indicated that the prevalence of Blastocystis sp. ST1, ST2 and ST3 was 20%, 20% and 60% in the child isolates, respectively. In contrast to human isolates, ST3 was not found in monkey isolates and the prevalence of ST1 and ST2 was 50% and 70%, respectively, including three mixed STs1 and 2 and one isolate not amplified by any STS primers, respectively. Since Blastocystis sp. ST2 has been reported as the most dominant genotype in the survey of Blastocystis infection among the various monkey species, sequence comparison of the 150bp variable region of the small subunit rRNA (SSU rRNA) gene was conducted among ST2 isolates of humans and monkeys. Sequence alignment of 24 clones developed from ST2 isolates of 4 humans and 4 monkeys showed three distinct subgroups, defined as ST2A, ST2B and ST2C. These three subgroups were shared between the child and monkey isolates. These results suggest that the local rhesus monkeys are a possible source of Blastocystis sp. ST2 infection of humans in Kathmandu.

  8. How cortical neurons help us see: visual recognition in the human brain

    OpenAIRE

    Blumberg, Julie; Kreiman, Gabriel

    2010-01-01

    Through a series of complex transformations, the pixel-like input to the retina is converted into rich visual perceptions that constitute an integral part of visual recognition. Multiple visual problems arise due to damage or developmental abnormalities in the cortex of the brain. Here, we provide an overview of how visual information is processed along the ventral visual cortex in the human brain. We discuss how neurophysiological recordings in macaque monkeys and in humans can help us under...

  9. A. Femoralis in the small Green Monkey(Cercopithecus aethiops sabeus

    Directory of Open Access Journals (Sweden)

    Blagojević Miloš

    2016-01-01

    Full Text Available The small Green Monkey (Cercopithecus aethiops sabeus in large groups inhabits the African savannah. The animals delivered to us were from East Africa, that is from Kenya, Uganda and Tanzania. The length of the animal is 110 cm, and the tail itself is 50 cm long. They can often be seen in Zoos. According to data, mostly by zoo gardens, these monkeys live for about 15 to 17 years, exceptionally for 20 years. The objective of our work was to investigate a part of their cardiovascular system so in that way to contribute to a better knowledge of this animal body structure and accordingly to comparative anatomy in general. The investigation included 6 Small Green Monkeys, of both gender, 3-4 years old, body weight 2000-3000 grams, obtained from The Institute for Virusology, vaccines and serums from Belgrade. For obtaining the hindlimb arterial vascularization, after exsanguination of the animal, contrast mass of gelatin coloured with tempera was injected into the abdominal aorta. After injecting, the blood vessels were prepared and photographed. In the Small Green Monkey, femoral artery (A. femoralis is an continuation of the external iliac artery (A. iliaca externa. The branches of the femoral artery are: A. profunda femoris, A. saphena, A. genus descendens and A. caudalis femoralis. A. profunda femoris separates to A. circumflexa femoris lateralis, Ramus muscularis and A. circumflexa femoris medialis. In humans A. femoralis branches into: A. epigastrica superficialis, A. circumflexa ilium superficialis, Aa. pudendae externae, A. profunda femoris and A. genus descendens (A. descendens genus. A. profunda femoris branches into: A. circumflexa femoris lateralis, A. circumflexa femoris medialis and Aa. perforantes. In domestic animals, mammals, the branches of the femoral artery (A. femoralis are: A. circumflexa femoris lateralis, A. saphena, A. genus descendens and Aa. caudales femoris In the Small Green Monkey, humans and domestic mammals A. femoralis

  10. Present and potential distribution of Snub-nosed Monkey

    DEFF Research Database (Denmark)

    Nüchel, Jonas; Bøcher, Peder Klith; Svenning, Jens-Christian

    are the Snub-nosed Monkeys (Rhinopithecus), a temperate-subtropical East Asian genus. We use species distribution modeling to assess the following question of key relevancy for conservation management of Rhinopithecus; 1. Which climatic factors determine the present distribution of Rhinopithecus within...... distribution of Rhinopithecus within the region, considering climate, habitat availability and the locations of nature reserves. Keywords: biodiversity, biogeography, conservation, China, snub-nosed monkey, rhinopithecus, primates, species distribution modeling...

  11. Time Course of Brain Network Reconfiguration Supporting Inhibitory Control.

    Science.gov (United States)

    Popov, Tzvetan; Westner, Britta U; Silton, Rebecca L; Sass, Sarah M; Spielberg, Jeffrey M; Rockstroh, Brigitte; Heller, Wendy; Miller, Gregory A

    2018-05-02

    Hemodynamic research has recently clarified key nodes and links in brain networks implementing inhibitory control. Although fMRI methods are optimized for identifying the structure of brain networks, the relatively slow temporal course of fMRI limits the ability to characterize network operation. The latter is crucial for developing a mechanistic understanding of how brain networks shift dynamically to support inhibitory control. To address this critical gap, we applied spectrally resolved Granger causality (GC) and random forest machine learning tools to human EEG data in two large samples of adults (test sample n = 96, replication sample n = 237, total N = 333, both sexes) who performed a color-word Stroop task. Time-frequency analysis confirmed that recruitment of inhibitory control accompanied by slower behavioral responses was related to changes in theta and alpha/beta power. GC analyses revealed directionally asymmetric exchanges within frontal and between frontal and parietal brain areas: top-down influence of superior frontal gyrus (SFG) over both dorsal ACC (dACC) and inferior frontal gyrus (IFG), dACC control over middle frontal gyrus (MFG), and frontal-parietal exchanges (IFG, precuneus, MFG). Predictive analytics confirmed a combination of behavioral and brain-derived variables as the best set of predictors of inhibitory control demands, with SFG theta bearing higher classification importance than dACC theta and posterior beta tracking the onset of behavioral response. The present results provide mechanistic insight into the biological implementation of a psychological phenomenon: inhibitory control is implemented by dynamic routing processes during which the target response is upregulated via theta-mediated effective connectivity within key PFC nodes and via beta-mediated motor preparation. SIGNIFICANCE STATEMENT Hemodynamic neuroimaging research has recently clarified regional structures in brain networks supporting inhibitory control. However, due to

  12. Species differences in [{sup 11}C]clorgyline binding in brain

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, Joanna S. E-mail: fowler@bnl.gov; Ding, Yu-Shin; Logan, Jean; MacGregor, Robert R.; Shea, Colleen; Garza, Victor; Gimi, Raomond; Volkow, Nora D.; Wang, Gene-Jack; Schlyer, David; Ferrieri, Richard; Gatley, S. John; Alexoff, David; Carter, Pauline; King, Payton; Pappas, Naomi; Arnett, Carroll D

    2001-10-01

    [{sup 11}C]Clorgyline selectively binds to MAO A in the human brain. This contrasts with a recent report that [{sup 11}C]clorgyline (in contrast to other labeled MAO A inhibitors) is not retained in the rhesus monkey brain . To explore this difference, we compared [{sup 11}C]clorgyline in the baboon brain before and after clorgyline pretreatment and we also synthesized deuterium substituted [{sup 11}C]clorgyline (and its nor-precursor) for comparison. [{sup 11}C]Clorgyline was not retained in the baboon brain nor was it influenced by clorgyline pretreatment or by deuterium substitution, contrasting to results in humans. This suggests a species difference in the susceptibility of MAO A to inhibition by clorgyline and represents an unusual example of where the behavior of a radiotracer in the baboon brain does not predict its behavior in the human brain.

  13. The effects of anti-VEGF drugs on the retinal pigment epithelium and inner segment after intravitreal injection in the monkeys

    Directory of Open Access Journals (Sweden)

    Nan Su

    2016-06-01

    Full Text Available AIM: To compare the effects on the retina inner segment and retinal pigment epithelium(RPEof intravitreally injecting bevacizumab, ranibizumab and aflibercept into monkey eyes.METHODS: Fourteen healthy cynomolgus monkeys(Macaca fascicularis, aged 3-8y,10 males,4 femaleswere raised at the Covance Laboratories under standard conditions. The 14 monkeys were grouped into 4 groups. Three of the groups with 4 monkeys each were injected intravitreally with one of the drugs, either bevacizumab, ranibizumab or aflibercept, while the 4th group with 2 monkeys served as a negative control. On 1d and 7d of injection, 2 monkeys from each drug treatment group were sacrificed under general anaesthesia and the 4 eyes were enucleated. All the enucleated eyes were fixed in formalin, embedded in paraffin wax, cut into 4.0 μm sections and deparaffinized according to standard procedures. Image-Pro Plus was used for all the photos to measure the content of vascular endothelial growth factor(VEGFin the inner segment and RPE. The ANOVA test from JMP10.0 statistical program was used to evaluate the results.RESULTS: Retinal sections were checked for their anti-VEGF immune reactivity. The untreated control samples had the highest level of VEGF in the RPE and inner segment. All of these three drugs can reduce the level of VEGF in the RPE and inner segment, but Avastin seems to be more effective than Eylea in this regard. Lucentis treatment at 1d seems to be more effective than Eylea at VEGF 1d. But at 7d, both Lucentis and Eylea have the same effect on reducing VEGF expression level in the RPE and inner segment.CONCLUSION: All of these three drugs can reduce the level of VEGF in the RPE and inner segment.

  14. What interests them in the pictures?--differences in eye-tracking between rhesus monkeys and humans.

    Science.gov (United States)

    Hu, Ying-Zhou; Jiang, Hui-Hui; Liu, Ci-Rong; Wang, Jian-Hong; Yu, Cheng-Yang; Carlson, Synnöve; Yang, Shang-Chuan; Saarinen, Veli-Matti; Rizak, Joshua D; Tian, Xiao-Guang; Tan, Hen; Chen, Zhu-Yue; Ma, Yuan-Ye; Hu, Xin-Tian

    2013-10-01

    Studies estimating eye movements have demonstrated that non-human primates have fixation patterns similar to humans at the first sight of a picture. In the current study, three sets of pictures containing monkeys, humans or both were presented to rhesus monkeys and humans. The eye movements on these pictures by the two species were recorded using a Tobii eye-tracking system. We found that monkeys paid more attention to the head and body in pictures containing monkeys, whereas both monkeys and humans paid more attention to the head in pictures containing humans. The humans always concentrated on the eyes and head in all the pictures, indicating the social role of facial cues in society. Although humans paid more attention to the hands than monkeys, both monkeys and humans were interested in the hands and what was being done with them in the pictures. This may suggest the importance and necessity of hands for survival. Finally, monkeys scored lower in eye-tracking when fixating on the pictures, as if they were less interested in looking at the screen than humans. The locations of fixation in monkeys may provide insight into the role of eye movements in an evolutionary context.

  15. The Connective Tissue Components of Optic Nerve Head Cupping in Monkey Experimental Glaucoma Part 1: Global Change

    Science.gov (United States)

    Yang, Hongli; Ren, Ruojin; Lockwood, Howard; Williams, Galen; Libertiaux, Vincent; Downs, Crawford; Gardiner, Stuart K.; Burgoyne, Claude F.

    2015-01-01

    Purpose To characterize optic nerve head (ONH) connective tissue change within 21 monkey experimental glaucoma (EG) eyes, so as to identify its principal components. Methods Animals were imaged three to five times at baseline then every 2 weeks following chronic unilateral IOP elevation, and euthanized early through end-stage confocal scanning laser tomographic change. Optic nerve heads were serial-sectioned, three-dimensionally (3D) reconstructed, delineated, and quantified. Overall EG versus control eye differences were assessed by general estimating equations (GEE). Significant, animal-specific, EG eye change was required to exceed the maximum physiologic intereye differences in six healthy animals. Results Overall EG eye change was significant (P connective tissue components of ONH “cupping” in monkey EG which serve as targets for longitudinally staging and phenotyping ONH connective tissue alteration within all forms of monkey and human optic neuropathy. PMID:26641545

  16. A hybrid BMI-based exoskeleton for paresis: EMG control for assisting arm movements.

    Science.gov (United States)

    Kawase, Toshihiro; Sakurada, Takeshi; Koike, Yasuharu; Kansaku, Kenji

    2017-02-01

    Brain-machine interface (BMI) technologies have succeeded in controlling robotic exoskeletons, enabling some paralyzed people to control their own arms and hands. We have developed an exoskeleton asynchronously controlled by EEG signals. In this study, to enable real-time control of the exoskeleton for paresis, we developed a hybrid system with EEG and EMG signals, and the EMG signals were used to estimate its joint angles. Eleven able-bodied subjects and two patients with upper cervical spinal cord injuries (SCIs) performed hand and arm movements, and the angles of the metacarpophalangeal (MP) joint of the index finger, wrist, and elbow were estimated from EMG signals using a formula that we derived to calculate joint angles from EMG signals, based on a musculoskeletal model. The formula was exploited to control the elbow of the exoskeleton after automatic adjustments. Four able-bodied subjects and a patient with upper cervical SCI wore an exoskeleton controlled using EMG signals and were required to perform hand and arm movements to carry and release a ball. Estimated angles of the MP joints of index fingers, wrists, and elbows were correlated well with the measured angles in 11 able-bodied subjects (correlation coefficients were 0.81  ±  0.09, 0.85  ±  0.09, and 0.76  ±  0.13, respectively) and the patients (e.g. 0.91  ±  0.01 in the elbow of a patient). Four able-bodied subjects successfully positioned their arms to adequate angles by extending their elbows and a joint of the exoskeleton, with root-mean-square errors  exoskeleton, successfully carried a ball to a goal in all 10 trials. A BMI-based exoskeleton for paralyzed arms and hands using real-time control was realized by designing a new method to estimate joint angles based on EMG signals, and these may be useful for practical rehabilitation and the support of daily actions.

  17. A hybrid BMI-based exoskeleton for paresis: EMG control for assisting arm movements

    Science.gov (United States)

    Kawase, Toshihiro; Sakurada, Takeshi; Koike, Yasuharu; Kansaku, Kenji

    2017-02-01

    Objective. Brain-machine interface (BMI) technologies have succeeded in controlling robotic exoskeletons, enabling some paralyzed people to control their own arms and hands. We have developed an exoskeleton asynchronously controlled by EEG signals. In this study, to enable real-time control of the exoskeleton for paresis, we developed a hybrid system with EEG and EMG signals, and the EMG signals were used to estimate its joint angles. Approach. Eleven able-bodied subjects and two patients with upper cervical spinal cord injuries (SCIs) performed hand and arm movements, and the angles of the metacarpophalangeal (MP) joint of the index finger, wrist, and elbow were estimated from EMG signals using a formula that we derived to calculate joint angles from EMG signals, based on a musculoskeletal model. The formula was exploited to control the elbow of the exoskeleton after automatic adjustments. Four able-bodied subjects and a patient with upper cervical SCI wore an exoskeleton controlled using EMG signals and were required to perform hand and arm movements to carry and release a ball. Main results. Estimated angles of the MP joints of index fingers, wrists, and elbows were correlated well with the measured angles in 11 able-bodied subjects (correlation coefficients were 0.81  ±  0.09, 0.85  ±  0.09, and 0.76  ±  0.13, respectively) and the patients (e.g. 0.91  ±  0.01 in the elbow of a patient). Four able-bodied subjects successfully positioned their arms to adequate angles by extending their elbows and a joint of the exoskeleton, with root-mean-square errors  exoskeleton, successfully carried a ball to a goal in all 10 trials. Significance. A BMI-based exoskeleton for paralyzed arms and hands using real-time control was realized by designing a new method to estimate joint angles based on EMG signals, and these may be useful for practical rehabilitation and the support of daily actions.

  18. X-ray induced translocations in premeiotic germ cells of monkeys

    International Nuclear Information System (INIS)

    Buul, P.P.W. van

    1991-01-01

    Induction of reciprocal translocations by various X-ray exposures was studied in spermatogonial stem cells of rhesus monkeys (Macaca mulatta) and stump-tailed Macaques (arctoides) by means of spermatocyte analysis many cell generations after irradiation. The yields of trans-locations recovered from irradiated stump-tailed macaques were lower than those observed in rhesus monkeys and represent in fact the lowest induction rates per Gy ever recorded for experimental mammals. In the rhesus monkey a humped dose-effect relationship was found with 1.a homo -geneous response with (pseudo-)linear kinetics below 1 Gy, 2.much more variability at higher doses, and 3.no induction at all at doses of 4 Gy and above. It is suggested that the post-irradiation proliferation differentiation pattern of surviving rhesus monkey spermatogonial stem cells is mainly responsible for these characteristics of the dose-response curve. (author). 41 refs.; 1 fig.; 4 tabs

  19. An online brain-machine interface using decoding of movement direction from the human electrocorticogram

    Science.gov (United States)

    Milekovic, Tomislav; Fischer, Jörg; Pistohl, Tobias; Ruescher, Johanna; Schulze-Bonhage, Andreas; Aertsen, Ad; Rickert, Jörn; Ball, Tonio; Mehring, Carsten

    2012-08-01

    A brain-machine interface (BMI) can be used to control movements of an artificial effector, e.g. movements of an arm prosthesis, by motor cortical signals that control the equivalent movements of the corresponding body part, e.g. arm movements. This approach has been successfully applied in monkeys and humans by accurately extracting parameters of movements from the spiking activity of multiple single neurons. We show that the same approach can be realized using brain activity measured directly from the surface of the human cortex using electrocorticography (ECoG). Five subjects, implanted with ECoG implants for the purpose of epilepsy assessment, took part in our study. Subjects used directionally dependent ECoG signals, recorded during active movements of a single arm, to control a computer cursor in one out of two directions. Significant BMI control was achieved in four out of five subjects with correct directional decoding in 69%-86% of the trials (75% on average). Our results demonstrate the feasibility of an online BMI using decoding of movement direction from human ECoG signals. Thus, to achieve such BMIs, ECoG signals might be used in conjunction with or as an alternative to intracortical neural signals.

  20. Antecedent control in the treatment of brain-injured clients.

    Science.gov (United States)

    Zencius, A H; Wesolowski, M D; Burke, W H; McQuade, P

    1989-01-01

    Three brain-injured clients failed to respond significantly to consequence management programmes designed to increase attendance, use of a cane, and to reduce unauthorized breaks. When antecedent stimulus control procedures were applied, attendance and use of a cane increased and unauthorized breaks decreased. The study shows that antecedent control may be the treatment of choice when treating brain-injured clients with memory loss.

  1. Geophagy in brown spider monkeys (Ateles hybridus) in a lowland tropical rainforest in Colombia.

    Science.gov (United States)

    Link, Andres; de Luna, Ana Gabriela; Arango, Ricardo; Diaz, Maria Clara

    2011-01-01

    Spider monkeys and howler monkeys are the only Neotropical primates that eat soil from mineral licks. Not all species within these genera visit mineral licks, and geophagy has been restricted to populations of Ateles belzebuth belzebuth,Ateles belzebuth chamek and Alouatta seniculus in western Amazonian rainforests. With the aid of a camera trap we studied the visitation patterns of a group of brown spider monkeys (Ateles hybridus) to a mineral lick at Serrania de Las Quinchas, in Colombia. Spider monkeys visited the lick frequently throughout the year, with a monthly average of 21.7 ± 7.2 visits per 100 days of camera trapping (n = 14 months). Spider monkeys visited the mineral lick almost always on days with no rain, or very little (<3 mm) rain, suggesting that proximate environmental variables might determine spider monkeys' decisions to come to the ground at the licks. This study expands the geographical occurrence of mineral lick use by spider monkeys providing additional data for future assessments on the biogeographical correlates of mineral lick use by platyrrhines. Copyright © 2011 S. Karger AG, Basel.

  2. Brain control and information transfer.

    Science.gov (United States)

    Tehovnik, Edward J; Chen, Lewis L

    2015-12-01

    In this review, we examine the importance of having a body as essential for the brain to transfer information about the outside world to generate appropriate motor responses. We discuss the context-dependent conditioning of the motor control neural circuits and its dependence on the completion of feedback loops, which is in close agreement with the insights of Hebb and colleagues, who have stressed that for learning to occur the body must be intact and able to interact with the outside world. Finally, we apply information theory to data from published studies to evaluate the robustness of the neuronal signals obtained by bypassing the body (as used for brain-machine interfaces) versus via the body to move in the world. We show that recording from a group of neurons that bypasses the body exhibits a vastly degraded level of transfer of information as compared to that of an entire brain using the body to engage in the normal execution of behaviour. We conclude that body sensations provide more than just feedback for movements; they sustain the necessary transfer of information as animals explore their environment, thereby creating associations through learning. This work has implications for the development of brain-machine interfaces used to move external devices.

  3. Characterization of the Sweet Taste Receptor Tas1r2 from an Old World Monkey Species Rhesus Monkey and Species-Dependent Activation of the Monomeric Receptor by an Intense Sweetener Perillartine.

    Directory of Open Access Journals (Sweden)

    Chenggu Cai

    Full Text Available Sweet state is a basic physiological sensation of humans and other mammals which is mediated by the broadly acting sweet taste receptor-the heterodimer of Tas1r2 (taste receptor type 1 member 2 and Tas1r3 (taste receptor type 1 member 3. Various sweeteners interact with either Tas1r2 or Tas1r3 and then activate the receptor. In this study, we cloned, expressed and functionally characterized the taste receptor Tas1r2 from a species of Old World monkeys, the rhesus monkey. Paired with the human TAS1R3, it was shown that the rhesus monkey Tas1r2 could respond to natural sugars, amino acids and their derivates. Furthermore, similar to human TAS1R2, rhesus monkey Tas1r2 could respond to artificial sweeteners and sweet-tasting proteins. However, the responses induced by rhesus monkey Tas1r2 could not be inhibited by the sweet inhibitor amiloride. Moreover, we found a species-dependent activation of the Tas1r2 monomeric receptors of human, rhesus monkey and squirrel monkey but not mouse by an intense sweetener perillartine. Molecular modeling and sequence analysis indicate that the receptor has the conserved domains and ligand-specific interactive residues, which have been identified in the characterized sweet taste receptors up to now. This is the first report of the functional characterization of sweet taste receptors from an Old World monkey species.

  4. Characterization of the Sweet Taste Receptor Tas1r2 from an Old World Monkey Species Rhesus Monkey and Species-Dependent Activation of the Monomeric Receptor by an Intense Sweetener Perillartine.

    Science.gov (United States)

    Cai, Chenggu; Jiang, Hua; Li, Lei; Liu, Tianming; Song, Xuejie; Liu, Bo

    2016-01-01

    Sweet state is a basic physiological sensation of humans and other mammals which is mediated by the broadly acting sweet taste receptor-the heterodimer of Tas1r2 (taste receptor type 1 member 2) and Tas1r3 (taste receptor type 1 member 3). Various sweeteners interact with either Tas1r2 or Tas1r3 and then activate the receptor. In this study, we cloned, expressed and functionally characterized the taste receptor Tas1r2 from a species of Old World monkeys, the rhesus monkey. Paired with the human TAS1R3, it was shown that the rhesus monkey Tas1r2 could respond to natural sugars, amino acids and their derivates. Furthermore, similar to human TAS1R2, rhesus monkey Tas1r2 could respond to artificial sweeteners and sweet-tasting proteins. However, the responses induced by rhesus monkey Tas1r2 could not be inhibited by the sweet inhibitor amiloride. Moreover, we found a species-dependent activation of the Tas1r2 monomeric receptors of human, rhesus monkey and squirrel monkey but not mouse by an intense sweetener perillartine. Molecular modeling and sequence analysis indicate that the receptor has the conserved domains and ligand-specific interactive residues, which have been identified in the characterized sweet taste receptors up to now. This is the first report of the functional characterization of sweet taste receptors from an Old World monkey species.

  5. Normal Anatomy, Histology, and Spontaneous Pathology of the Nasal Cavity of the Cynomolgus Monkey (Macaca fascicularis).

    Science.gov (United States)

    Chamanza, Ronnie; Taylor, Ian; Gregori, Michela; Hill, Colin; Swan, Mark; Goodchild, Joel; Goodchild, Kane; Schofield, Jane; Aldous, Mark; Mowat, Vasanthi

    2016-07-01

    The evaluation of inhalation studies in monkeys is often hampered by the scarcity of published information on the relevant nasal anatomy and pathology. We examined nasal cavities of 114 control cynomolgus monkeys from 11 inhalation studies evaluated 2008 to 2013, in order to characterize and document the anatomic features and spontaneous pathology. Compared to other laboratory animals, the cynomolgus monkey has a relatively simple nose with 2 unbranched, dorsoventrally stacked turbinates, large maxillary sinuses, and a nasal septum that continues into the nasopharynx. The vomeronasal organ is absent, but nasopalatine ducts are present. Microscopically, the nasal epithelium is thicker than that in rodents, and the respiratory (RE) and transitional epithelium (TE) rest on a thick basal lamina. Generally, squamous epithelia and TE line the vestibule, RE, the main chamber and nasopharynx, olfactory epithelium, a small caudodorsal region, while TE is observed intermittently along the passages. Relatively high incidences of spontaneous pathology findings, some resembling induced lesions, were observed and included inflammation, luminal exudate, scabs, squamous and respiratory metaplasia or hyperplasia, mucous cell hyperplasia/metaplasia, and olfactory degeneration. Regions of epithelial transition were the most affected. This information is considered helpful in the histopathology evaluation and interpretation of inhalation studies in monkeys. © The Author(s) 2016.

  6. Heterochrony and cross-species intersensory matching by infant vervet monkeys.

    Directory of Open Access Journals (Sweden)

    Shahin Zangenehpour

    Full Text Available Understanding the evolutionary origins of a phenotype requires understanding the relationship between ontogenetic and phylogenetic processes. Human infants have been shown to undergo a process of perceptual narrowing during their first year of life, whereby their intersensory ability to match the faces and voices of another species declines as they get older. We investigated the evolutionary origins of this behavioral phenotype by examining whether or not this developmental process occurs in non-human primates as well.We tested the ability of infant vervet monkeys (Cercopithecus aethiops, ranging in age from 23 to 65 weeks, to match the faces and voices of another non-human primate species (the rhesus monkey, Macaca mulatta. Even though the vervets had no prior exposure to rhesus monkey faces and vocalizations, our findings show that infant vervets can, in fact, recognize the correspondence between rhesus monkey faces and voices (but indicate that they do so by looking at the non-matching face for a greater proportion of overall looking time, and can do so well beyond the age of perceptual narrowing in human infants. Our results further suggest that the pattern of matching by vervet monkeys is influenced by the emotional saliency of the Face+Voice combination. That is, although they looked at the non-matching screen for Face+Voice combinations, they switched to looking at the matching screen when the Voice was replaced with a complex tone of equal duration. Furthermore, an analysis of pupillary responses revealed that their pupils showed greater dilation when looking at the matching natural face/voice combination versus the face/tone combination.Because the infant vervets in the current study exhibited cross-species intersensory matching far later in development than do human infants, our findings suggest either that intersensory perceptual narrowing does not occur in Old World monkeys or that it occurs later in development. We argue that these

  7. An Improved Unscented Kalman Filter Based Decoder for Cortical Brain-Machine Interfaces.

    Science.gov (United States)

    Li, Simin; Li, Jie; Li, Zheng

    2016-01-01

    Brain-machine interfaces (BMIs) seek to connect brains with machines or computers directly, for application in areas such as prosthesis control. For this application, the accuracy of the decoding of movement intentions is crucial. We aim to improve accuracy by designing a better encoding model of primary motor cortical activity during hand movements and combining this with decoder engineering refinements, resulting in a new unscented Kalman filter based decoder, UKF2, which improves upon our previous unscented Kalman filter decoder, UKF1. The new encoding model includes novel acceleration magnitude, position-velocity interaction, and target-cursor-distance features (the decoder does not require target position as input, it is decoded). We add a novel probabilistic velocity threshold to better determine the user's intent to move. We combine these improvements with several other refinements suggested by others in the field. Data from two Rhesus monkeys indicate that the UKF2 generates offline reconstructions of hand movements (mean CC 0.851) significantly more accurately than the UKF1 (0.833) and the popular position-velocity Kalman filter (0.812). The encoding model of the UKF2 could predict the instantaneous firing rate of neurons (mean CC 0.210), given kinematic variables and past spiking, better than the encoding models of these two decoders (UKF1: 0.138, p-v Kalman: 0.098). In closed-loop experiments where each monkey controlled a computer cursor with each decoder in turn, the UKF2 facilitated faster task completion (mean 1.56 s vs. 2.05 s) and higher Fitts's Law bit rate (mean 0.738 bit/s vs. 0.584 bit/s) than the UKF1. These results suggest that the modeling and decoder engineering refinements of the UKF2 improve decoding performance. We believe they can be used to enhance other decoders as well.

  8. Movement disorders induced in monkeys by chronic haloperidol treatment

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, B; Santelli, S; Lusink, G

    1977-01-01

    After several months of treatment, Cebus apella, Cebus albifrons, and Saimiri sciurea monkeys maintained on haloperidol, in doses of 0.5 or 1.0 mg/kg orally 5 days per week, began to display severe movement disorders, typically 1 to 6 h post-drug. Cebus monkeys exhibited violent, uncontrolled movements that flung the animals about the cage. Such episodes usually lasted only a few minutes, recurring several times during the period following drug ingestion. Writhing and bizarre postures dominated the response in S. sciurea. Cessation of drug treatment produced no distinctive after-effects. When tested as long as 508 days after the last administration, however, Cebus monkeys responded to haloperidol with several episodes of hyperkinesis, even at challenge doses considerably lower than those in the original treatment.

  9. Adapting Parcellation Schemes to Study Fetal Brain Connectivity in Serial Imaging Studies

    DEFF Research Database (Denmark)

    Cheng, Xi; Wilm, Jakob; Seshamani, Sharmishtaa

    2013-01-01

    A crucial step in studying brain connectivity is the definition of the Regions Of Interest (ROI's) which are considered as nodes of a network graph. These ROI's identified in structural imaging reflect consistent functional regions in the anatomies being compared. However in serial studies...... of the developing fetal brain such functional and associated structural markers are not consistently present over time. In this study we adapt two non-atlas based parcellation schemes to study the development of connectivity networks of a fetal monkey brain using Diffusion Weighted Imaging techniques. Results...... demonstrate that the fetal brain network exhibits small-world characteristics and a pattern of increased cluster coefficients and decreased global efficiency. These findings may provide a route to creating a new biomarker for healthy fetal brain development....

  10. Placental Transport of Zidovudine in the Rhesus Monkey

    Science.gov (United States)

    King, Thomas S.; Henderson, George I.; Schenker, Steven; Schenken, Robert S.

    1993-01-01

    Objective: This study was undertaken to characterize the pharmacokinetics of zidovudine (ZDV) and ZDV-glucuronide (ZDVG) in the material and :fetal circulations of the rhesus monkey. Methods: Cannulas were placed in the maternal external jugular and the fetal internal jugular and carotid artery in 8 pregnant monkeys at .120–130 days gestation. ZDV (3.5 mg/kg) was administered to 5 monkeys and ZDVG (3.5 mg/kg) to 3 monkeys as single intravenous bolus infusions through the maternal catheter. Maternal and fetal blood , samples were collected every 20 min for the first 2 h and then every hour for the next 4 h. Maternal and fetal concentrations of ZDV and ZDVG were determined using high, performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Results: In monkeys who received ZDV, the terminal half-life (T1/2) for ZDV was 37±15 and 33 ± 13 min in the maternal and fetal compartments, respectively. The apparent T1/2 for maternal ZDVG was 124 ± 44 and 142 ± 50 min in the maternal and fetal compartments, respectively. Peak levels of ZDV and ZDVG in the fetal compartment were reached 40 min after injection. The mean fetal/maternal concentration ratios for ZDV and ZDVG ranged from 0.20 ± 0.20 at 20 min to a maximum of 0.74 ± 1.0 at 120 min and from 0.28 ± 0.08 at 20 min to 1.4 ± 1.3 at 180 min, respectively. In monkeys who received ZDVG, the T1/2 for ZDWG in the maternal and fetal compartments was 47 ± 26 and 119 ± 164 min, respectively. ZDVG reached its peak in the fetal compartment at 60 min post-injection. The fetal/maternal rafio ranged from 0.08 ± 0.11 at 20 min to 4.2 ± 4.2 at 180 min post-injection. Conclusions: These data demonstrate that 1) ZDV and ZDVG rapidly cross the placenta to the fetal compartment, 2) ZDV crosses more rapidly than ZDVG, and 3) some metabolism of ZDV to ZDVG occurs in the fetal compartment. PMID:18475334

  11. Automatic Incubator-type Temperature Control System for Brain Hypothermia Treatment

    Science.gov (United States)

    Gaohua, Lu; Wakamatsu, Hidetoshi

    An automatic air-cooling incubator is proposed to replace the manual water-cooling blanket to control the brain tissue temperature for brain hypothermia treatment. Its feasibility is theoretically discussed as follows: First, an adult patient with the cooling incubator is modeled as a linear dynamical patient-incubator biothermal system. The patient is represented by an 18-compartment structure and described by its state equations. The air-cooling incubator provides almost same cooling effect as the water-cooling blanket, if a light breeze of speed around 3 m/s is circulated in the incubator. Then, in order to control the brain temperature automatically, an adaptive-optimal control algorithm is adopted, while the patient-blanket therapeutic system is considered as a reference model. Finally, the brain temperature of the patient-incubator biothermal system is controlled to follow up the given reference temperature course, in which an adaptive algorithm is confirmed useful for unknown environmental change and/or metabolic rate change of the patient in the incubating system. Thus, the present work ensures the development of the automatic air-cooling incubator for a better temperature regulation of the brain hypothermia treatment in ICU.

  12. Pathogenesis of Rift Valley Fever in Rhesus Monkeys: Role of Interferon Response

    Science.gov (United States)

    1990-01-01

    hemorrhagic fever characterized by epistaxis, petechial to purpuric cutaneous lesions, anorexia, and vomiting prior to death. The 14 remaining monkeys survived...DMI, FILE Copy Arch Virol (1990) 110: 195-212 Amhivesirology ( by Springer-Verlag 1990 00 N Pathogenesis of Rift Valley fever in rhesus monkeys: (NI...inoculated intravenously with Rift Valley fever (RVF) virus presented clinical disease syndromes similar to human cases of RVF. All 17 infected monkeys

  13. Distribution of [1-14C]acrylonitrile in rat and monkey

    International Nuclear Information System (INIS)

    Sandberg, E.Ch.; Slanina, P.

    1980-01-01

    The distribution of [1- 14 C]acrylonitrile (ACN) in rat and monkey has been studied by whole-body autoradiography, after being administered orally and intravenously to rats and orally to monkeys. Uptake of radioactivity was seen in the blood, liver, kidney, lung, adrenal cortex and stomach mucosa. (Auth.)

  14. SV40 host-substituted variants: a new look at the monkey DNA inserts and recombinant junctions.

    Science.gov (United States)

    Singer, Maxine; Winocour, Ernest

    2011-04-10

    The available monkey genomic data banks were examined in order to determine the chromosomal locations of the host DNA inserts in 8 host-substituted SV40 variant DNAs. Five of the 8 variants contained more than one linked monkey DNA insert per tandem repeat unit and in all cases but one, the 19 monkey DNA inserts in the 8 variants mapped to different locations in the monkey genome. The 50 parental DNAs (32 monkey and 18 SV40 DNA segments) which spanned the crossover and flanking regions that participated in monkey/monkey and monkey/SV40 recombinations were characterized by substantial levels of microhomology of up to 8 nucleotides in length; the parental DNAs also exhibited direct and inverted repeats at or adjacent to the crossover sequences. We discuss how the host-substituted SV40 variants arose and the nature of the recombination mechanisms involved. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Development of rapid multistep carbon-11 radiosynthesis of the myeloperoxidase inhibitor AZD3241 to assess brain exposure by PET microdosing

    International Nuclear Information System (INIS)

    Johnström, Peter; Bergman, Linda; Varnäs, Katarina; Malmquist, Jonas; Halldin, Christer; Farde, Lars

    2015-01-01

    Introduction: The myeloperoxidase inhibitor AZD3241 has been selected as a candidate drug currently being developed to delay progression in patients with neurodegenerative brain disorders. Part of the decision tree for translation of AZD3241 into clinical studies included the need for assessment of brain exposure in non-human primates by PET microdosing. For that purpose a rapid multistep method for 11 C-labeling of AZD3241 was developed. Methods: AZD3241 was labeled in the thio-carbonyl position starting from [ 11 C]potassium cyanide in a 4-step procedure using microwave assisted heating. In the first step [ 11 C]potassium cyanide was converted to [ 11 C]potassium thiocyanate followed by reaction with benzoyl chloride to yield benzoyl [ 11 C]isothiocyanate. The benzoyl [ 11 C]isothiocyanate was subsequently reacted with the precursor ethyl 3-(2-isopropoxyethylamino)-1H-pyrrole-2-carboxylate and the formed intermediate underwent a base catalyzed cyclization to obtain [ 11 C]AZD3241 in the final step. To assess [ 11 C]AZD3241 brain exposure PET measurements were performed in three cynomolgus monkeys. Results: [ 11 C]AZD3241 was produced in good and reproducible radiochemical yield 710 ± 294 MBq (mean ± SD, n = 7). Total time of synthesis was 60 min from end of bombardment. The specific radioactivity was 9 ± 4 GBq/μmol and the radiochemical purity was > 98%. Following iv administration of [ 11 C]AZD3241 there was a rapid presence of radioactivity in brain in each of the three monkeys. The distribution of [ 11 C]AZD3241 to brain was fast and a C max of 1.9 to 2.6% of the injected radioactivity was observed within 1.5 min. [ 11 C]AZD3241 was homogeneously distributed in brain. Conclusion: The MPO inhibitor AZD3241 was successfully labeled with carbon-11 in a challenging 4-step procedure in good radiochemical yield allowing PET microdosing studies in cynomolgus monkey. [ 11 C]AZD3241 rapidly entered brain and confirmed adequate brain exposure to support translation

  16. Loss of metabolites from monkey striatum during PET with FDOPA

    DEFF Research Database (Denmark)

    Cumming, P; Munk, O L; Doudet, D

    2001-01-01

    constants using data recorded during 240 min of FDOPA circulation in normal monkeys and in monkeys with unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesions. Use of the extended models increased the magnitudes of K(D)(i) and k(D)(3) in striatum; in the case of k(D)(3), variance...... of the estimate was substantially improved upon correction for metabolite loss. The rate constants for metabolite loss were higher in MPTP-lesioned monkey striatum than in normal striatum. The high correlation between individual estimates of k(Lin)(cl) and k(DA)(9) suggests that both rate constants reveal loss...

  17. Electroencephalography(EEG)-based instinctive brain-control of a quadruped locomotion robot.

    Science.gov (United States)

    Jia, Wenchuan; Huang, Dandan; Luo, Xin; Pu, Huayan; Chen, Xuedong; Bai, Ou

    2012-01-01

    Artificial intelligence and bionic control have been applied in electroencephalography (EEG)-based robot system, to execute complex brain-control task. Nevertheless, due to technical limitations of the EEG decoding, the brain-computer interface (BCI) protocol is often complex, and the mapping between the EEG signal and the practical instructions lack of logic associated, which restrict the user's actual use. This paper presents a strategy that can be used to control a quadruped locomotion robot by user's instinctive action, based on five kinds of movement related neurophysiological signal. In actual use, the user drives or imagines the limbs/wrists action to generate EEG signal to adjust the real movement of the robot according to his/her own motor reflex of the robot locomotion. This method is easy for real use, as the user generates the brain-control signal through the instinctive reaction. By adopting the behavioral control of learning and evolution based on the proposed strategy, complex movement task may be realized by instinctive brain-control.

  18. Peripersonal space in the brain.

    Science.gov (United States)

    di Pellegrino, Giuseppe; Làdavas, Elisabetta

    2015-01-01

    Research in neuroscience reveals that the brain constructs multiple representation of space. Here, we primarily focus on peripersonal space (PPS) representation, the region of space immediately surrounding our bodies and in which objects can be grasped and manipulated. We review convergent results from several generations of studies, including neurophysiological studies in animals, neuropsychological investigations in monkeys and brain-damaged patients with spatial cognition disorders, as well as recent neuroimaging experiments in neurologically normal individuals. Collectively, these studies show that the primate brain constructs multiple, rapidly modifiable representations of space, centered on different body parts (i.e., hand-centered, head-centered, and trunk-centered), which arise through extensive multisensory interactions within a set of interconnected parietal and frontal regions. PPS representations are pivotal in the sensory guidance of motor behavior, allowing us to interact with objects and, as demonstrated by recent studies, with other people in the space around us. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on signal transduction pathway-related protein expression in liver and cerebrum of rhesus monkey

    Energy Technology Data Exchange (ETDEWEB)

    Ohta, Mari; Akema, Satoshi; Tsuzuki, Masami; Kubota, Shunichiro [Tokyo Univ. (Japan); Korenaga, Tatsumi; Fukusato, Toshio [Teikyo Univ. of School of Medicine, Tokyo (Japan); Asaoka, Kazuo [Kyoto Univ. (Japan); Murata, Nobuo [Teikyo Univ. of School of Medicine, Kawasaki (Japan); Nomizu, Motoyoshi [Hokkaido Univ., Sapporo (Japan); Arima, Akihiro [Shin Nippon Biomedical Laboratories, Ltd., Kagoshima (Japan)

    2004-09-15

    2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to produce a wide range of toxic and biochemical effects in experimental animals, including immunological dysfunctions, chloracne, tetragenecity and carcinogenesis. Recently, the potential impact of dioxins on neurological disorders with particular focus on attention deficit hyperactivity disorder (ADHD) are concerned. Although a lot of information is available from studies in rodents, not much is known of the low dose effects of TCDD in non-human primates. In higher animals, dioxins are metabolized slowly, as evidenced by the estimated TCDD half-life of 5.8 to 14.1 years. Therefore, it is necessary to investigate the long-term effects of TCDD on human health. Considering the pronounced species differences observed in some studies of TCDD, the studies using primates are needed for assessment of TCDD exposure on human health. We have been studying the metabolism and the effects of single administration of TCDD on pregnant monkey (F0) and F1 rhesus monkey. The focus of the present study is to study the effects of TCDD on signal transduction pathway-related protein levels in various organs, especially in liver and brain of F0 monkeys.

  20. Construction and evaluation of novel rhesus monkey adenovirus vaccine vectors.

    Science.gov (United States)

    Abbink, Peter; Maxfield, Lori F; Ng'ang'a, David; Borducchi, Erica N; Iampietro, M Justin; Bricault, Christine A; Teigler, Jeffrey E; Blackmore, Stephen; Parenteau, Lily; Wagh, Kshitij; Handley, Scott A; Zhao, Guoyan; Virgin, Herbert W; Korber, Bette; Barouch, Dan H

    2015-02-01

    Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. The phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. Here we describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved to have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors. Although there have been substantial efforts in the development of vaccine vectors from human and chimpanzee adenoviruses, far less is known about rhesus monkey adenoviruses. In this report, we describe the isolation and vectorization of three novel rhesus monkey adenoviruses. These vectors exhibit virologic and immunologic characteristics that make them attractive as potential candidate vaccine vectors for both HIV-1 and other pathogens. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  1. Brain-Computer Interface Controlled Cyborg: Establishing a Functional Information Transfer Pathway from Human Brain to Cockroach Brain.

    Science.gov (United States)

    Li, Guangye; Zhang, Dingguo

    2016-01-01

    An all-chain-wireless brain-to-brain system (BTBS), which enabled motion control of a cyborg cockroach via human brain, was developed in this work. Steady-state visual evoked potential (SSVEP) based brain-computer interface (BCI) was used in this system for recognizing human motion intention and an optimization algorithm was proposed in SSVEP to improve online performance of the BCI. The cyborg cockroach was developed by surgically integrating a portable microstimulator that could generate invasive electrical nerve stimulation. Through Bluetooth communication, specific electrical pulse trains could be triggered from the microstimulator by BCI commands and were sent through the antenna nerve to stimulate the brain of cockroach. Serial experiments were designed and conducted to test overall performance of the BTBS with six human subjects and three cockroaches. The experimental results showed that the online classification accuracy of three-mode BCI increased from 72.86% to 78.56% by 5.70% using the optimization algorithm and the mean response accuracy of the cyborgs using this system reached 89.5%. Moreover, the results also showed that the cyborg could be navigated by the human brain to complete walking along an S-shape track with the success rate of about 20%, suggesting the proposed BTBS established a feasible functional information transfer pathway from the human brain to the cockroach brain.

  2. Nutritional manipulation of primate retinas, III: Effects of lutein or zeaxanthin supplementation on adipose tissue and retina of xanthophyll-free monkeys.

    Science.gov (United States)

    Johnson, Elizabeth J; Neuringer, Martha; Russell, Robert M; Schalch, Wolfgang; Snodderly, D Max

    2005-02-01

    Macular pigment (MP) is composed of the xanthophylls lutein (L) and zeaxanthin (Z) and may help to prevent age-related macular degeneration or retard its progression. In this study the effects of L or Z supplementation on carotenoid levels was examined in serum, adipose tissue, and retina in rhesus monkeys with no previous intake of xanthophylls. From birth to 7 to 16 years of age, 18 rhesus monkeys were fed semipurified diets containing all essential nutrients but no xanthophylls. Six were supplemented with pure L and 6 with pure Z at 3.9 micromol/kg per day for 24 to 101 weeks. At baseline and at 4- to 12-week intervals, carotenoids in adipose tissue were measured by HPLC. At study completion, carotenoids in serum and retina (central 4 mm, 8-mm annulus, and the periphery) were determined. Results were compared with data from control monkeys fed a standard laboratory diet. Monkeys fed xanthophyll-free diets had no L or Z in serum or tissues. After L or Z supplementation, serum and adipose tissue concentrations significantly increased in the supplemented groups. Both L and 3R,3'S-Z (RSZ or meso-Z, not present in the diet) were incorporated into retinas of monkeys supplemented with L, with RSZ present only in the macula (central 4 mm). All-trans Z, but no RSZ, accumulated in retinas of monkeys supplemented with Z. L is the precursor of RSZ, a major component of macular pigment. Xanthophyll-free monkeys can accumulate retinal xanthophylls and provide a valuable model for examining their uptake and conversion.

  3. A comparative analysis of global and local processing of hierarchical visual stimuli in young children (Homo sapiens) and monkeys (Cebus apella).

    Science.gov (United States)

    De Lillo, Carlo; Spinozzi, Giovanna; Truppa, Valentina; Naylor, Donna M

    2005-05-01

    Results obtained with preschool children (Homo sapiens) were compared with results previously obtained from capuchin monkeys (Cebus apella) in matching-to-sample tasks featuring hierarchical visual stimuli. In Experiment 1, monkeys, in contrast with children, showed an advantage in matching the stimuli on the basis of their local features. These results were replicated in a 2nd experiment in which control trials enabled the authors to rule out that children used spurious cues to solve the matching task. In a 3rd experiment featuring conditions in which the density of the stimuli was manipulated, monkeys' accuracy in the processing of the global shape of the stimuli was negatively affected by the separation of the local elements, whereas children's performance was robust across testing conditions. Children's response latencies revealed a global precedence in the 2nd and 3rd experiments. These results show differences in the processing of hierarchical stimuli by humans and monkeys that emerge early during childhood. 2005 APA, all rights reserved

  4. Serotonin transporter occupancy by escitalopram and citalopram in the non-human primate brain: a [(11)C]MADAM PET study.

    Science.gov (United States)

    Finnema, Sjoerd J; Halldin, Christer; Bang-Andersen, Benny; Bundgaard, Christoffer; Farde, Lars

    2015-11-01

    A number of serotonin receptor positron emission tomography (PET) radioligands have been shown to be sensitive to changes in extracellular serotonin concentration, in a generalization of the well-known dopamine competition model. High doses of selective serotonin reuptake inhibitors (SSRIs) decrease serotonin receptor availability in monkey brain, consistent with increased serotonin concentrations. However, two recent studies on healthy human subjects, using a single, lower and clinically relevant SSRI dose, showed increased cortical serotonin receptor radioligand binding, suggesting potential decreases in serotonin concentration in projection regions when initiating treatment. The cross-species differential SSRI effect may be partly explained by serotonin transporter (SERT) occupancy in monkey brain being higher than is clinically relevant. We here determine SERT occupancy after single doses of escitalopram or citalopram by conducting PET measurements with [(11)C]MADAM in monkeys. Relationships between dose, plasma concentration and SERT occupancy were estimated by one-site binding analyses. Binding affinity was expressed as dose (ID50) or plasma concentration (K i) where 50 % SERT occupancy was achieved. Estimated ID50 and K i values were 0.020 mg/kg and 9.6 nmol/L for escitalopram and 0.059 mg/kg and 9.7 nmol/L for citalopram, respectively. Obtained K i values are comparable to values reported in humans. Escitalopram or citalopram doses nearly saturated SERT in previous monkey studies which examined serotonin sensitivity of receptor radioligands. PET-measured cross-species differential effects of SSRI on cortical serotonin concentration may thus be related to SSRI dose. Future monkey studies using SSRI doses inducing clinically relevant SERT occupancy may further illuminate the delayed onset of SSRI therapeutic effects.

  5. Human-Rhesus Monkey conflict at Rampur Village under Monohardi Upazila in Narsingdi District of Bangladesh

    Directory of Open Access Journals (Sweden)

    M.F. Ahsan

    2014-06-01

    Full Text Available Human-Rhesus monkey conflicts were recorded at Rampur Village under Khidirpur Union Parishad of Monohardi upazila under Narsingdi District in Bangladesh from April to September 2012. There were three groups of Rhesus monkeys living in the area. The focal study group comprised 26 individuals (4 adult males, 6 adult females, 10 juveniles and 6 infants. The monkeys consumed parts of 10 plant species. From the questionnaire survey, it was found that the greatest damage caused by monkeys was on betel leaf vines and the least damage on vegetables. Eighty percent respondents opted to conserve the monkeys and 20% opined status quo. Some restricted areas (especially khas lands may be identified and planted with some fruit trees for survival of monkeys and for reducing conflicts with humans.

  6. Alpha and gamma oscillations characterize feedback and feedforward processing in monkey visual cortex.

    Science.gov (United States)

    van Kerkoerle, Timo; Self, Matthew W; Dagnino, Bruno; Gariel-Mathis, Marie-Alice; Poort, Jasper; van der Togt, Chris; Roelfsema, Pieter R

    2014-10-07

    Cognitive functions rely on the coordinated activity of neurons in many brain regions, but the interactions between cortical areas are not yet well understood. Here we investigated whether low-frequency (α) and high-frequency (γ) oscillations characterize different directions of information flow in monkey visual cortex. We recorded from all layers of the primary visual cortex (V1) and found that γ-waves are initiated in input layer 4 and propagate to the deep and superficial layers of cortex, whereas α-waves propagate in the opposite direction. Simultaneous recordings from V1 and downstream area V4 confirmed that γ- and α-waves propagate in the feedforward and feedback direction, respectively. Microstimulation in V1 elicited γ-oscillations in V4, whereas microstimulation in V4 elicited α-oscillations in V1, thus providing causal evidence for the opposite propagation of these rhythms. Furthermore, blocking NMDA receptors, thought to be involved in feedback processing, suppressed α while boosting γ. These results provide new insights into the relation between brain rhythms and cognition.

  7. Dexterous Control of Seven Functional Hand Movements Using Cortically-Controlled Transcutaneous Muscle Stimulation in a Person With Tetraplegia

    Directory of Open Access Journals (Sweden)

    Samuel C. Colachis

    2018-04-01

    Full Text Available Individuals with tetraplegia identify restoration of hand function as a critical, unmet need to regain their independence and improve quality of life. Brain-Computer Interface (BCI-controlled Functional Electrical Stimulation (FES technology addresses this need by reconnecting the brain with paralyzed limbs to restore function. In this study, we quantified performance of an intuitive, cortically-controlled, transcutaneous FES system on standardized object manipulation tasks from the Grasp and Release Test (GRT. We found that a tetraplegic individual could use the system to control up to seven functional hand movements, each with >95% individual accuracy. He was able to select one movement from the possible seven movements available to him and use it to appropriately manipulate all GRT objects in real-time using naturalistic grasps. With the use of the system, the participant not only improved his GRT performance over his baseline, demonstrating an increase in number of transfers for all objects except the Block, but also significantly improved transfer times for the heaviest objects (videocassette (VHS, Can. Analysis of underlying motor cortex neural representations associated with the hand grasp states revealed an overlap or non-separability in neural activation patterns for similarly shaped objects that affected BCI-FES performance. These results suggest that motor cortex neural representations for functional grips are likely more related to hand shape and force required to hold objects, rather than to the objects themselves. These results, demonstrating multiple, naturalistic functional hand movements with the BCI-FES, constitute a further step toward translating BCI-FES technologies from research devices to clinical neuroprosthetics.

  8. Accumulation, Biotransformation, Histopathology and Paralysis in the Pacific Calico Scallop Argopecten ventricosus by the Paralyzing Toxins of the Dinoflagellate Gymnodinium catenatum

    Directory of Open Access Journals (Sweden)

    Rosalba Alonso-Rodriguez

    2012-05-01

    Full Text Available The dinoflagellate Gymnodinium catenatum produces paralyzing shellfish poisons that are consumed and accumulated by bivalves. We performed short-term feeding experiments to examine ingestion, accumulation, biotransformation, histopathology, and paralysis in the juvenile Pacific calico scallop Argopecten ventricosus that consume this dinoflagellate. Depletion of algal cells was measured in closed systems. Histopathological preparations were microscopically analyzed. Paralysis was observed and the time of recovery recorded. Accumulation and possible biotransformation of toxins were measured by HPLC analysis. Feeding activity in treated scallops showed that scallops produced pseudofeces, ingestion rates decreased at 8 h; approximately 60% of the scallops were paralyzed and melanin production and hemocyte aggregation were observed in several tissues at 15 h. HPLC analysis showed that the only toxins present in the dinoflagellates and scallops were the N-sulfo-carbamoyl toxins (C1, C2; after hydrolysis, the carbamate toxins (epimers GTX2/3 were present. C1 and C2 toxins were most common in the mantle, followed by the digestive gland and stomach-complex, adductor muscle, kidney and rectum group, and finally, gills. Toxin profiles in scallop tissue were similar to the dinoflagellate; biotransformations were not present in the scallops in this short-term feeding experiment.

  9. How cortical neurons help us see: visual recognition in the human brain

    Science.gov (United States)

    Blumberg, Julie; Kreiman, Gabriel

    2010-01-01

    Through a series of complex transformations, the pixel-like input to the retina is converted into rich visual perceptions that constitute an integral part of visual recognition. Multiple visual problems arise due to damage or developmental abnormalities in the cortex of the brain. Here, we provide an overview of how visual information is processed along the ventral visual cortex in the human brain. We discuss how neurophysiological recordings in macaque monkeys and in humans can help us understand the computations performed by visual cortex. PMID:20811161

  10. When vision guides movement: a functional imaging study of the monkey brain.

    Science.gov (United States)

    Gregoriou, Georgia G; Savaki, Helen E

    2003-07-01

    Goal-directed reaching requires a precise neural representation of the arm position and the target location. Parietal and frontal cortical areas rely on visual, somatosensory, and motor signals to guide the reaching arm to the desired position in space. To dissociate the regions processing these signals, we applied the quantitative [(14)C]-deoxyglucose method on monkeys reaching either in the light or in the dark. Nonvisual (somatosensory and memory-related) guidance of the arm, during reaching in the dark, induced activation of discrete regions in the parietal, premotor, and motor cortices. These included the dorsal part of the medial bank of the intraparietal sulcus, the ventral premotor area F4, the dorsal premotor area F2 below the superior precentral dimple, and the primary somatosensory and motor cortices. Additional parietal and premotor regions comprising the ventral intraparietal cortex, ventral premotor area F5, and the ventral part of dorsal premotor area F2 were activated by visual guidance of the arm during reaching in the light. This study provides evidence that different regions of the parieto-premotor circuit process the visual, somatosensory, and motor-memory-related signals which guide the moving arm.

  11. Response of sublethally irradiated monkeys to a replicating viral antigen

    International Nuclear Information System (INIS)

    Hilmas, D.E.; Spertzel, R.O.

    1975-01-01

    Temporal effects of exposure to sublethal, total-body x radiation (400 R) on responses to vaccination with the attenuated Venezuelan equine encephalomyelitis vaccine virus, TC-83, were examined in rhesus monkeys. Viremia, often with delayed onset, was prolonged even when irradiation preceded vaccination by 28 days. Virus titers were increased, particularly in groups irradiated 4 or 7 days before vaccination. Delay in appearance of hemagglutination-inhibition and serum-neutralizing antibody correlated closely with persistence of viremia in irradiated-vaccinated monkeys. The temporal course of antibody response was markedly affected by the interval between irradiation and injection of this replicating antigen. With longer intervals between irradiation and vaccination, the somewhat depressed antibody responses approached normal or surpassed those of nonirradiated monkeys. Vaccination 14 days after radiation exposure resulted in lethality to 8 of 12 monkeys, apparently as a result of secondary infection. The additional lymphopenic stress due to the effect of TC-83, superimposed on the severely depressed hematopoietic competence at 14 days, undoubtedly contributed to this increased susceptibility to latent infection

  12. Monkeying around: Use of Survey Monkey as a Tool for School Social Work

    Science.gov (United States)

    Massat, Carol Rippey; McKay, Cassandra; Moses, Helene

    2009-01-01

    This article describes the use of an online survey tool called Survey Monkey, which can be used by school social workers and school social work educators for evaluation of practice, needs assessment, and program evaluation. Examples of questions are given. Principles of writing good survey questions are described. (Contains 2 tables and 1…

  13. The protons of space and brain tumors: I. Clinical and dosimetric considerations

    International Nuclear Information System (INIS)

    Dalrymple, G.V.; Nagle, W.A.; Moss, A.J.; Cavin, L.A.; Broadwater, J.R.; McGuire, E.L.; Eason, C.S.

    1989-01-01

    Almost 25 years ago a large group of Rhesus monkeys were irradiated with protons (32--2300 MeV). The experiments were designed: (1) To estimate the RBE of protons, per se, and (2) To provide some estimate of the hazards of the radiation environment of space. The initial results showed the RBE to be about 1.0 for acute radiation effects (mortality, hematologic changes, etc). The colony has been maintained at Brooks AFB, TX since irradiation. The survivors of 55 MeV proton irradiation have developed a very high incidence of Glioblastoma multiforme, a highly malignant primary brain tumor. These tumors appeared 1--20 yrs after surface doses of 400--800 rads. Reconstruction of the dosimetry suggests that some areas within the brain may have received doses of 1500--2500 rads. More than 30 radiation induced Glioblastomas have been reported in human patients who had received therapeutic head irradiation. The radiation doses required to induce Glioblastoma were of the same order of magnitude as required to induce Glioblastoma in the Rhesus monkey

  14. Alternative Splicing of AMPA subunits in Prefrontal Cortical Fields of Cynomolgus Monkeys following Chronic Ethanol Self-Administration

    Directory of Open Access Journals (Sweden)

    Glen eAcosta

    2012-01-01

    Full Text Available Functional impairment of the orbital and medial prefrontal cortex underlies deficits in executive control that characterize addictive disorders, including alcohol addiction. Previous studies indicate that alcohol alters glutamate neurotransmission and one substrate of these effects may be through the reconfiguration of the subunits constituting ionotropic glutamate receptor (iGluR complexes. Glutamatergic transmission is integral to cortico-cortical and cortico-subcortical communication and alcohol-induced changes in the abundance of the receptor subunits and/or their splice variants may result in critical functional impairments of prefrontal cortex in alcohol dependence. To this end, the effects of chronic ethanol self-administration on glutamate receptor ionotropic AMPA (GRIA subunit variant and kainate (GRIK subunit mRNA expression were studied in the orbitofrontal cortex (OFC, dorsolateral prefrontal cortex (DLPFC and anterior cingulate cortex (ACC of male cynomolgus monkeys. In DLPFC, total AMPA splice variant expression and total kainate receptor subunit expression were significantly decreased in alcohol drinking monkeys. Expression levels of GRIA3 flip and flop and GRIA4 flop mRNAs in this region were positively correlated with daily ethanol intake and blood ethanol concentrations averaged over the six months prior to necropsy. In OFC, AMPA subunit splice variant expression was reduced in the alcohol treated group. GRIA2 flop mRNA levels in this region were positively correlated with daily ethanol intake and blood ethanol concentrations averaged over the six months prior to necropsy. Results from these studies provide further evidence of transcriptional regulation of iGluR subunits in the primate brain following chronic alcohol self-administration. Additional studies examining the cellular localization of such effects in the framework of primate prefrontal cortical circuitry are warranted.

  15. The neonatal marmoset monkey ovary is very primitive exhibiting many oogonia

    Science.gov (United States)

    Fereydouni, B; Drummer, C; Aeckerle, N; Schlatt, S; Behr, R

    2014-01-01

    Oogonia are characterized by diploidy and mitotic proliferation. Human and mouse oogonia express several factors such as OCT4, which are characteristic of pluripotent cells. In human, almost all oogonia enter meiosis between weeks 9 and 22 of prenatal development or undergo mitotic arrest and subsequent elimination from the ovary. As a consequence, neonatal human ovaries generally lack oogonia. The same was found in neonatal ovaries of the rhesus monkey, a representative of the old world monkeys (Catarrhini). By contrast, proliferating oogonia were found in adult prosimians (now called Strepsirrhini), which is a group of ‘lower’ primates. The common marmoset monkey (Callithrix jacchus) belongs to the new world monkeys (Platyrrhini) and is increasingly used in reproductive biology and stem cell research. However, ovarian development in the marmoset monkey has not been widely investigated. Herein, we show that the neonatal marmoset ovary has an extremely immature histological appearance compared with the human ovary. It contains numerous oogonia expressing the pluripotency factors OCT4A, SALL4, and LIN28A (LIN28). The pluripotency factor-positive germ cells also express the proliferation marker MKI67 (Ki-67), which has previously been shown in the human ovary to be restricted to premeiotic germ cells. Together, the data demonstrate the primitiveness of the neonatal marmoset ovary compared with human. This study may introduce the marmoset monkey as a non-human primate model to experimentally study the aspects of primate primitive gonad development, follicle assembly, and germ cell biology in vivo. PMID:24840529

  16. Efficient foot motor control by Neymar’s brain

    Directory of Open Access Journals (Sweden)

    Eiichi eNaito

    2014-08-01

    Full Text Available How very long-term (over many years motor skill training shapes internal motor representation remains poorly understood. We provide valuable evidence that the football brain of Neymar da Silva Santos Júnior (the Brasilian footballer recruits very limited neural resources in the motor-cortical foot regions during foot movements. We scanned his brain activity with a 3-tesla functional magnetic resonance imaging (fMRI while he rotated his right ankle at 1Hz. We also scanned brain activity when three other age-controlled professional footballers, two top-athlete swimmers and one amateur footballer performed the identical task. A comparison was made between Neymar’s brain activity with that obtained from the others. We found activations in the left medial-wall foot motor regions during the foot movements consistently across all participants. However, the size and intensity of medial-wall activity was smaller in the four professional footballers than in the three other participants, despite no difference in amount of foot movement. Surprisingly, the reduced recruitment of medial-wall foot motor regions became apparent in Neymar. His medial-wall activity was smallest among all participants with absolutely no difference in amount of foot movement. Neymar may efficiently control given foot movements probably by largely conserving motor-cortical neural resources. We discuss this possibility in terms of over-years motor skill training effect, use-dependent plasticity, and efficient motor control.

  17. Event-based proactive interference in rhesus monkeys.

    Science.gov (United States)

    Devkar, Deepna T; Wright, Anthony A

    2016-10-01

    Three rhesus monkeys (Macaca mulatta) were tested in a same/different memory task for proactive interference (PI) from prior trials. PI occurs when a previous sample stimulus appears as a test stimulus on a later trial, does not match the current sample stimulus, and the wrong response "same" is made. Trial-unique pictures (scenes, objects, animals, etc.) were used on most trials, except on trials where the test stimulus matched potentially interfering sample stimulus from a prior trial (1, 2, 4, 8, or 16 trials prior). Greater interference occurred when fewer trials separated interference and test. PI functions showed a continuum of interference. Delays between sample and test stimuli and intertrial intervals were manipulated to test how PI might vary as a function of elapsed time. Contrary to a similar study with pigeons, these time manipulations had no discernable effect on the monkey's PI, as shown by compete overlap of PI functions with no statistical differences or interactions. These results suggested that interference was strictly based upon the number of intervening events (trials with other pictures) without regard to elapsed time. The monkeys' apparent event-based interference was further supported by retesting with a novel set of 1,024 pictures. PI from novel pictures 1 or 2 trials prior was greater than from familiar pictures, a familiar set of 1,024 pictures. Moreover, when potentially interfering novel stimuli were 16 trials prior, performance accuracy was actually greater than accuracy on baseline trials (no interference), suggesting that remembering stimuli from 16 trials prior was a cue that this stimulus was not the sample stimulus on the current trial-a somewhat surprising conclusion particularly given monkeys.

  18. Stable isotope ratios indicate diet and habitat use in New World monkeys.

    Science.gov (United States)

    Schoeninger, M J; Iwaniec, U T; Glander, K E

    1997-05-01

    This paper demonstrates the use of stable isotope ratios of carbon and nitrogen in animal tissue for indicating aspects of species behavioral strategy. We analyzed hair from individuals representing four species of New World monkeys (Alouatta palliata, the mantled howler; Ateles geoffroyi, the spider monkey; Cebus capucinus, the capuchin; and Brachyteles arachnoides, the woolly-spider monkey or muriqui) for delta 13C and delta 15N using previously developed methods. There are no significant differences in either carbon or nitrogen ratios between sexes, sampling year, or year of analysis. Seasonal differences in delta 13C reached a low level of significance but do not affect general patterns. Variation within species was similar to that recorded previously within single individuals. The omega 13C data show a bimodal distribution with significant difference between the means. The two monkey populations living in an evergreen forest were similar to each other and different from the other two monkey populations that inhabited dry, deciduous forests. This bimodal distribution is independent of any particular species' diet and reflects the level of leaf cover in the two types of forest. The delta 15N data display three significantly different modes. The omnivorous capuchins were most positive reflecting a trophic level offset. The spider monkeys and the muriquis were similar to one another and significantly more positive than the howlers. This distribution among totally herbivorous species correlates with the ingestion of legumes by the howler monkey population. In combination, these data indicate that museum-curated primate material can be analyzed to yield information on forest cover and diet in populations and species lacking behavioral data.

  19. Telemetric assessment of social and single housing: Evaluation of electrocardiographic intervals in jacketed cynomolgus monkeys.

    Science.gov (United States)

    Kaiser, Robert A; Tichenor, Stephen D; Regalia, Douglas E; York, Kristina; Holzgrefe, Henry H

    2015-01-01

    Proactive efforts to socially house laboratory animals are a contemporary, important focus for enhancing animal welfare. Jacketing cynomolgus monkeys has been traditionally considered an exclusionary criterion for social housing based on unsubstantiated concerns that study conduct or telemetry equipment might be compromised. Our objective was to evaluate the effects of jacketing naïve, adolescent cynomolgus monkeys in different single and social housing types based on parallel comparisons of heart rate. Eight naive cynomolgus monkeys were randomized into pairs and ECG data were collected for 24h from each animal in each housing condition using a crossover design. Caging paradigms consisted of standard individual, standard pair, quaternary pair (4 linked cages), and European-style pair housing in non-sequential order varied by pair to control for possible time bias. Dosing and blood collection procedures were performed to characterize any effects of housing on ECG data during study conduct. There was no increase in the incidence of equipment damage in pair vs. individually housed animals. Further, animals in all 4 housing paradigms showed similar acclimation assessed as heart rate (mean 139-154 beats per minute), and maintained similar diurnal rhythms, with an expected slowing of the heart rate at night (aggregate lights out HR 110±4bpm compared to daytime 146±7bpm). This study demonstrates the effects of different social access and housing types on the study-naïve cynomolgus monkeys during jacketed cardiovascular telemetry data collection in a repeat-dose toxicology study design. There were no discernible effects of social housing on baseline ECG parameters collected via jacketed telemetry, and all animals maintained expected diurnal rhythms in all housing settings tested. These data demonstrate that cynomolgus monkeys can be socially housed during data collection as a standard practice, consistent with global efforts to improve study animal welfare. Copyright

  20. Predictive and tempo-flexible synchronization to a visual metronome in monkeys.

    Science.gov (United States)

    Takeya, Ryuji; Kameda, Masashi; Patel, Aniruddh D; Tanaka, Masaki

    2017-07-21

    Predictive and tempo-flexible synchronization to an auditory beat is a fundamental component of human music. To date, only certain vocal learning species show this behaviour spontaneously. Prior research training macaques (vocal non-learners) to tap to an auditory or visual metronome found their movements to be largely reactive, not predictive. Does this reflect the lack of capacity for predictive synchronization in monkeys, or lack of motivation to exhibit this behaviour? To discriminate these possibilities, we trained monkeys to make synchronized eye movements to a visual metronome. We found that monkeys could generate predictive saccades synchronized to periodic visual stimuli when an immediate reward was given for every predictive movement. This behaviour generalized to novel tempi, and the monkeys could maintain the tempo internally. Furthermore, monkeys could flexibly switch from predictive to reactive saccades when a reward was given for each reactive response. In contrast, when humans were asked to make a sequence of reactive saccades to a visual metronome, they often unintentionally generated predictive movements. These results suggest that even vocal non-learners may have the capacity for predictive and tempo-flexible synchronization to a beat, but that only certain vocal learning species are intrinsically motivated to do it.

  1. Immunotoxicological Evaluation of Genetically Modified Rice Expressing Cry1Ab/Ac Protein (TT51-1) by a 6-Month Feeding Study on Cynomolgus Monkeys

    OpenAIRE

    Tan, Xiaoyan; Zhou, Xiaobing; Tang, Yao; Lv, Jianjun; Zhang, Lin; Sun, Li; Yang, Yanwei; Miao, Yufa; Jiang, Hua; Chen, Gaofeng; Huang, Zhiying; Wang, Xue

    2016-01-01

    The present study was performed to evaluate the food safety of TT51-1, a new type of genetically modified rice that expresses the Cry1Ab/Ac protein (Bt toxin) and is highly resistant to most lepidopteran pests. Sixteen male and 16 female cynomolgus monkeys were randomly divided into four groups: conventional rice (non-genetically modified rice, non-GM rice), positive control, 17.5% genetically modified rice (GM rice) and 70% GM rice. Monkeys in the non-GM rice, positive control, and GM rice g...

  2. Discovery of a Cynomolgus Monkey Family With Retinitis Pigmentosa.

    Science.gov (United States)

    Ikeda, Yasuhiro; Nishiguchi, Koji M; Miya, Fuyuki; Shimozawa, Nobuhiro; Funatsu, Jun; Nakatake, Shunji; Fujiwara, Kohta; Tachibana, Takashi; Murakami, Yusuke; Hisatomi, Toshio; Yoshida, Shigeo; Yasutomi, Yasuhiro; Tsunoda, Tatsuhiko; Nakazawa, Toru; Ishibashi, Tatsuro; Sonoda, Koh-Hei

    2018-02-01

    To accelerate the development of new therapies, an inherited retinal degeneration model in a nonhuman primate would be useful to confirm the efficacy in preclinical studies. In this study, we describe the discovery of retinitis pigmentosa in a cynomolgus monkey (Macaca fascicularis) pedigree. First, screening with fundus photography was performed on 1443 monkeys at the Tsukuba Primate Research Center. Ophthalmic examinations, such as indirect ophthalmoscopy, ERGs using RETeval, and optic coherent tomography (OCT) measurement, were then performed to confirm diagnosis. Retinal degeneration with cystoid macular edema was observed in both eyes of one 14-year-old female monkey. In her examinations, the full-field ERGs were nonrecordable and the outer layer of the retina in the parafoveal area was not visible on OCT imaging. Moreover, less frequent pigmentary retinal anomalies also were observed in her 3-year-old nephew. His full-field ERGs were almost nonrecordable and the outer layer was not visible in the peripheral retina. His father was her cousin (the son of her mother's older brother) and his mother was her younger half-sibling sister with a different father. The hereditary nature is highly probable (autosomal recessive inheritance suspected). However, whole-exome analysis performed identified no pathogenic mutations in these monkeys.

  3. Neural Monkey: An Open-source Tool for Sequence Learning

    Directory of Open Access Journals (Sweden)

    Helcl Jindřich

    2017-04-01

    Full Text Available In this paper, we announce the development of Neural Monkey – an open-source neural machine translation (NMT and general sequence-to-sequence learning system built over the TensorFlow machine learning library. The system provides a high-level API tailored for fast prototyping of complex architectures with multiple sequence encoders and decoders. Models’ overall architecture is specified in easy-to-read configuration files. The long-term goal of the Neural Monkey project is to create and maintain a growing collection of implementations of recently proposed components or methods, and therefore it is designed to be easily extensible. Trained models can be deployed either for batch data processing or as a web service. In the presented paper, we describe the design of the system and introduce the reader to running experiments using Neural Monkey.

  4. Brain-muscle-computer interface: mobile-phone prototype development and testing.

    Science.gov (United States)

    Vernon, Scott; Joshi, Sanjay S

    2011-07-01

    We report prototype development and testing of a new mobile-phone-based brain-muscle-computer interface for severely paralyzed persons, based on previous results from our group showing that humans may actively create specified power levels in two separate frequency bands of a single surface electromyography (sEMG) signal. EMG activity on the surface of a single face muscle site (auricularis superior) is recorded with a standard electrode. This analog electrical signal is imported into an Android-based mobile phone and digitized via an internal A/D converter. The digital signal is split, and then simultaneously filtered with two band-pass filters to extract total power within two separate frequency bands. The user-modulated power in each frequency band serves as two separate control channels for machine control. After signal processing, the Android phone sends commands to external devices via a Bluetooth interface. Users are trained to use the device via visually based operant conditioning, with simple cursor-to-target activities on the phone screen. The mobile-phone prototype interface is formally evaluated on a single advanced Spinal Muscle Atrophy subject, who has successfully used the interface in his home in evaluation trials and for remote control of a television. Development of this new device will not only guide future interface design for community use, but will also serve as an information technology bridge for in situ data collection to quantify human sEMG manipulation abilities for a relevant population.

  5. Monkey liver cytochrome P450 2C19 is involved in R- and S-warfarin 7-hydroxylation.

    Science.gov (United States)

    Hosoi, Yoshio; Uno, Yasuhiro; Murayama, Norie; Fujino, Hideki; Shukuya, Mitsunori; Iwasaki, Kazuhide; Shimizu, Makiko; Utoh, Masahiro; Yamazaki, Hiroshi

    2012-12-15

    Cynomolgus monkeys are widely used as primate models in preclinical studies. However, some differences are occasionally seen between monkeys and humans in the activities of cytochrome P450 enzymes. R- and S-warfarin are model substrates for stereoselective oxidation in humans. In this current research, the activities of monkey liver microsomes and 14 recombinantly expressed monkey cytochrome P450 enzymes were analyzed with respect to R- and S-warfarin 6- and 7-hydroxylation. Monkey liver microsomes efficiently mediated both R- and S-warfarin 7-hydroxylation, in contrast to human liver microsomes, which preferentially catalyzed S-warfarin 7-hydroxylation. R-Warfarin 7-hydroxylation activities in monkey liver microsomes were not inhibited by α-naphthoflavone or ketoconazole, and were roughly correlated with P450 2C19 levels and flurbiprofen 4-hydroxylation activities in microsomes from 20 monkey livers. In contrast, S-warfarin 7-hydroxylation activities were not correlated with the four marker drug oxidation activities used. Among the 14 recombinantly expressed monkey P450 enzymes tested, P450 2C19 had the highest activities for R- and S-warfarin 7-hydroxylations. Monkey P450 3A4 and 3A5 slowly mediated R- and S-warfarin 6-hydroxylations. Kinetic analysis revealed that monkey P450 2C19 had high V(max) and low K(m) values for R-warfarin 7-hydroxylation, comparable to those for monkey liver microsomes. Monkey P450 2C19 also mediated S-warfarin 7-hydroxylation with V(max) and V(max)/K(m) values comparable to those for recombinant human P450 2C9. R-warfarin could dock favorably into monkey P450 2C19 modeled. These results collectively suggest high activities for monkey liver P450 2C19 toward R- and S-warfarin 6- and 7-hydroxylation in contrast to the saturation kinetics of human P450 2C9-mediated S-warfarin 7-hydroxylation. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. In vivo evaluation of carbon-11-labelled non-sarcosine-based glycine transporter 1 inhibitors in mice and conscious monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Toyohara, Jun [Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan 260-8670 (Japan); Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan 173-0022 (Japan); Ishiwata, Kiichi; Sakata, Muneyuki [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan 173-0022 (Japan); Wu, Jin [Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan 260-8670 (Japan); Nishiyama, Shingo; Tsukada, Hideo [Central Research Laboratory, Hamamatsu Photonics K.K., Shizuoka, Japan 434-8601 (Japan); Hashimoto, Kenji, E-mail: hashimoto@faculty.chiba-u.j [Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan 260-8670 (Japan)

    2011-05-15

    Introduction: Glycine transporter 1 (GlyT-1) is an attractive target in positron emission tomography (PET) studies. Here, we report the in vivo evaluation of three carbon-11-labelled non-sarcosine-type GlyT-1 inhibitors - [{sup 11}C]SA1, [{sup 11}C]SA2 and [{sup 11}C]SA3 - as novel PET tracers for GlyT-1. Methods: The regional brain distributions of the three compounds in mice were studied at baseline and under receptor-blockade conditions with co-injection of carrier loading or pretreatment with an excess of selective GlyT-1 inhibitors (ALX-5407 and SSR504734). Metabolic stability was investigated by radio high-performance liquid chromatography. Dynamic PET scans in conscious monkeys were performed with/without selective GlyT-1 inhibitors. Results: The IC{sub 50} values of SA1, SA2 and SA3 were 9.0, 6400 and 39.7 nM, respectively. The regional brain uptakes of [{sup 11}C]SA1 and [{sup 11}C]SA3 in mice were heterogeneous and consistent with the known distribution of GlyT-1. [{sup 11}C]SA2 showed low and homogeneous uptake in the brain. Most radioactivity in the brain was detected in unchanged form, although peripherally these compounds were degraded. Carrier loading decreased the uptake of [{sup 11}C]SA1 in GlyT-1-rich regions. However, similar reductions were not observed with [{sup 11}C]SA3. Pretreatment with ALX-5407 decreased the uptake of [{sup 11}C]SA1 in GlyT-1-rich regions. In the monkey at baseline, regional brain uptake of [{sup 11}C]SA1 was heterogeneous and consistent with the known GlyT-1 distribution. Pretreatment with selective GlyT-1 inhibitors significantly decreased the distribution volume ratio of [{sup 11}C] SA1 in GlyT-1-rich regions. Conclusions: [{sup 11}C]SA1 has the most suitable profile among the three carbon-11-labelled GlyT-1 inhibitors. Lead optimization of [{sup 11}C]SA1 structure will be required to achieve in vivo selective GlyT-1 imaging.

  7. Observability and Controllability of Networks: Symmetry in Representations of Brains and Controllers for Epidemics

    Science.gov (United States)

    Schiff, Steven

    Observability and controllability are essential concepts to the design of predictive observer models and feedback controllers of networked systems. We present a numerical and group representational framework, to quantify the observability and controllability of nonlinear networks with explicit symmetries that shows the connection between symmetries and nonlinear measures of observability and controllability. In addition to the topology of brain networks, we have advanced our ability to represent network nodes within the brain using conservation principles and more accurate biophysics that unifies the dynamics of spikes, seizures, and spreading depression. Lastly, we show how symmetries in controller design can be applied to infectious disease epidemics. NIH Grants 1R01EB014641, 1DP1HD086071.

  8. Patient's breath controls comfort devices

    Science.gov (United States)

    Schrader, M.; Carpenter, B.; Nichols, C. D.

    1972-01-01

    Patient assist system for totally disabled persons was developed which permits a person, so paralyzed as to be unable to move, to activate by breathing, a call system to summon assistance, turn the page of a book, ajust his bed, or do any one of a number of other things. System consists of patient assist control and breath actuated switch.

  9. Brain-Computer Interfaces With Multi-Sensory Feedback for Stroke Rehabilitation: A Case Study.

    Science.gov (United States)

    Irimia, Danut C; Cho, Woosang; Ortner, Rupert; Allison, Brendan Z; Ignat, Bogdan E; Edlinger, Guenter; Guger, Christoph

    2017-11-01

    Conventional therapies do not provide paralyzed patients with closed-loop sensorimotor integration for motor rehabilitation. This work presents the recoveriX system, a hardware and software platform that combines a motor imagery (MI)-based brain-computer interface (BCI), functional electrical stimulation (FES), and visual feedback technologies for a complete sensorimotor closed-loop therapy system for poststroke rehabilitation. The proposed system was tested on two chronic stroke patients in a clinical environment. The patients were instructed to imagine the movement of either the left or right hand in random order. During these two MI tasks, two types of feedback were provided: a bar extending to the left or right side of a monitor as visual feedback and passive hand opening stimulated from FES as proprioceptive feedback. Both types of feedback relied on the BCI classification result achieved using common spatial patterns and a linear discriminant analysis classifier. After 10 sessions of recoveriX training, one patient partially regained control of wrist extension in her paretic wrist and the other patient increased the range of middle finger movement by 1 cm. A controlled group study is planned with a new version of the recoveriX system, which will have several improvements. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  10. Comparison of oxime reactivation and aging of nerve agent-inhibited monkey and human acetylcholinesterases.

    Science.gov (United States)

    Luo, Chunyuan; Tong, Min; Maxwell, Donald M; Saxena, Ashima

    2008-09-25

    Non-human primates are valuable animal models that are used for the evaluation of nerve agent toxicity as well as antidotes and results from animal experiments are extrapolated to humans. It has been demonstrated that the efficacy of an oxime primarily depends on its ability to reactivate nerve agent-inhibited acetylcholinesterase (AChE). If the in vitro oxime reactivation of nerve agent-inhibited animal AChE is similar to that of human AChE, it is likely that the results of an in vivo animal study will reliably extrapolate to humans. Therefore, the goal of this study was to compare the aging and reactivation of human and different monkey (Rhesus, Cynomolgus, and African Green) AChEs inhibited by GF, GD, and VR. The oximes examined include the traditional oxime 2-PAM, two H-oximes HI-6 and HLo-7, and the new candidate oxime MMB4. Results indicate that oxime reactivation of all three monkey AChEs was very similar to human AChE. The maximum difference in the second-order reactivation rate constant between human and three monkey AChEs or between AChEs from different monkey species was 5-fold. Aging rate constants of GF-, GD-, and VR-inhibited monkey AChEs were very similar to human AChE except for GF-inhibited monkey AChEs, which aged 2-3 times faster than the human enzyme. The results of this study suggest that all three monkey species are suitable animal models for nerve agent antidote evaluation since monkey AChEs possess similar biochemical/pharmacological properties to human AChE.

  11. Formal monkey linguistics : The debate

    NARCIS (Netherlands)

    Schlenker, Philippe; Chemla, Emmanuel; Schel, Anne M.|info:eu-repo/dai/nl/413333450; Fuller, James; Gautier, Jean Pierre; Kuhn, Jeremy; Veselinović, Dunja; Arnold, Kate; Cäsar, Cristiane; Keenan, Sumir; Lemasson, Alban; Ouattara, Karim; Ryder, Robin; Zuberbühler, Klaus

    2016-01-01

    We explain why general techniques from formal linguistics can and should be applied to the analysis of monkey communication - in the areas of syntax and especially semantics. An informed look at our recent proposals shows that such techniques needn't rely excessively on categories of human language:

  12. Reward-based hypertension control by a synthetic brain-dopamine interface.

    Science.gov (United States)

    Rössger, Katrin; Charpin-El Hamri, Ghislaine; Fussenegger, Martin

    2013-11-05

    Synthetic biology has significantly advanced the design of synthetic trigger-controlled devices that can reprogram mammalian cells to interface with complex metabolic activities. In the brain, the neurotransmitter dopamine coordinates communication with target neurons via a set of dopamine receptors that control behavior associated with reward-driven learning. This dopamine transmission has recently been suggested to increase central sympathetic outflow, resulting in plasma dopamine levels that correlate with corresponding brain activities. By functionally rewiring the human dopamine receptor D1 (DRD1) via the second messenger cyclic adenosine monophosphate (cAMP) to synthetic promoters containing cAMP response element-binding protein 1(CREB1)-specific cAMP-responsive operator modules, we have designed a synthetic dopamine-sensitive transcription controller that reversibly fine-tunes specific target gene expression at physiologically relevant brain-derived plasma dopamine levels. Following implantation of circuit-transgenic human cell lines insulated by semipermeable immunoprotective microcontainers into mice, the designer device interfaced with dopamine-specific brain activities and produced a systemic expression response when the animal's reward system was stimulated by food, sexual arousal, or addictive drugs. Reward-triggered brain activities were able to remotely program peripheral therapeutic implants to produce sufficient amounts of the atrial natriuretic peptide, which reduced the blood pressure of hypertensive mice to the normal physiologic range. Seamless control of therapeutic transgenes by subconscious behavior may provide opportunities for treatment strategies of the future.

  13. Estrogen regulation of microcephaly genes and evolution of brain sexual dimorphism in primates.

    Science.gov (United States)

    Shi, Lei; Lin, Qiang; Su, Bing

    2015-06-30

    Sexual dimorphism in brain size is common among primates, including humans, apes and some Old World monkeys. In these species, the brain size of males is generally larger than that of females. Curiously, this dimorphism has persisted over the course of primate evolution and human origin, but there is no explanation for the underlying genetic controls that have maintained this disparity in brain size. In the present study, we tested the effect of the female hormone (estradiol) on seven genes known to be related to brain size in both humans and nonhuman primates, and we identified half estrogen responsive elements (half EREs) in the promoter regions of four genes (MCPH1, ASPM, CDK5RAP2 and WDR62). Likewise, at sequence level, it appears that these half EREs are generally conserved across primates. Later testing via a reporter gene assay and cell-based endogenous expression measurement revealed that estradiol could significantly suppress the expression of the four affected genes involved in brain size. More intriguingly, when the half EREs were deleted from the promoters, the suppression effect disappeared, suggesting that the half EREs mediate the regulation of estradiol on the brain size genes. We next replicated these experiments using promoter sequences from chimpanzees and rhesus macaques, and observed a similar suppressive effect of estradiol on gene expression, suggesting that this mechanism is conserved among primate species that exhibit brain size dimorphism. Brain size dimorphism among certain primates, including humans, is likely regulated by estrogen through its sex-dependent suppression of brain size genes during development.

  14. Theory of feedback controlled brain stimulations for Parkinson's disease

    Science.gov (United States)

    Sanzeni, A.; Celani, A.; Tiana, G.; Vergassola, M.

    2016-01-01

    Limb tremor and other debilitating symptoms caused by the neurodegenerative Parkinson's disease are currently treated by administering drugs and by fixed-frequency deep brain stimulation. The latter interferes directly with the brain dynamics by delivering electrical impulses to neurons in the subthalamic nucleus. While deep brain stimulation has shown therapeutic benefits in many instances, its mechanism is still unclear. Since its understanding could lead to improved protocols of stimulation and feedback control, we have studied a mathematical model of the many-body neural network dynamics controlling the dynamics of the basal ganglia. On the basis of the results obtained from the model, we propose a new procedure of active stimulation, that depends on the feedback of the network and that respects the constraints imposed by existing technology. We show by numerical simulations that the new protocol outperforms the standard ones for deep brain stimulation and we suggest future experiments that could further improve the feedback procedure.

  15. Towards Effective Non-Invasive Brain-Computer Interfaces Dedicated to Gait Rehabilitation Systems

    Directory of Open Access Journals (Sweden)

    Thierry Castermans

    2013-12-01

    Full Text Available In the last few years, significant progress has been made in the field of walk rehabilitation. Motor cortex signals in bipedal monkeys have been interpreted to predict walk kinematics. Epidural electrical stimulation in rats and in one young paraplegic has been realized to partially restore motor control after spinal cord injury. However, these experimental trials are far from being applicable to all patients suffering from motor impairments. Therefore, it is thought that more simple rehabilitation systems are desirable in the meanwhile. The goal of this review is to describe and summarize the progress made in the development of non-invasive brain-computer interfaces dedicated to motor rehabilitation systems. In the first part, the main principles of human locomotion control are presented. The paper then focuses on the mechanisms of supra-spinal centers active during gait, including results from electroencephalography, functional brain imaging technologies [near-infrared spectroscopy (NIRS, functional magnetic resonance imaging (fMRI, positron-emission tomography (PET, single-photon emission-computed tomography (SPECT] and invasive studies. The first brain-computer interface (BCI applications to gait rehabilitation are then presented, with a discussion about the different strategies developed in the field. The challenges to raise for future systems are identified and discussed. Finally, we present some proposals to address these challenges, in order to contribute to the improvement of BCI for gait rehabilitation.

  16. Plasmodium simium/Plasmodium vivax infections in southern brown howler monkeys from the Atlantic Forest

    Directory of Open Access Journals (Sweden)

    Daniela Camargos Costa

    2014-08-01

    Full Text Available Blood infection by the simian parasite, Plasmodium simium, was identified in captive (n = 45, 4.4% and in wild Alouatta clamitans monkeys (n = 20, 35% from the Atlantic Forest of southern Brazil. A single malaria infection was symptomatic and the monkey presented clinical and haematological alterations. A high frequency of Plasmodium vivax-specific antibodies was detected among these monkeys, with 87% of the monkeys testing positive against P. vivax antigens. These findings highlight the possibility of malaria as a zoonosis in the remaining Atlantic Forest and its impact on the epidemiology of the disease.

  17. Effects of ionizing radiation on male germ cells of crab-eating monkey

    International Nuclear Information System (INIS)

    Okamoto, Masanori; Kitazuma, Masayuki; Tobari, Izuo

    1989-01-01

    Effects of ionizing radiation on sperm concentration, testicular volume, and sperm shape of the crab-eating monkey were studied by using acute and low dose-rate gamma-ray and X-ray. The animals were acutely irradiated with 0.25-3.00 Gy with Cs-137 gamma-ray at a dose-rate of 0.25 Gy/min. Sperm concentrations were decreased with time after irradiation in a dose-dependent fashion. The time required for the lowest concentration of sperm depended on radiation doses. A linear dose-response relationship was seen for sperm concentrations. In comparing the present results in monkeys to previous results in mice and golden hamsters, the sensitivity of spermatogenic cells in killing effect of gamma ray varied in the following order: monkeys>hamsters>mice. The present monkeys were also subjected to whole-body irradiation with 0.3-1.5 Gy of Cs-137 gamma-ray at 1.8 x 10 -5 Gy/min, for the purpose of estimating low-dose rate irradiation on sperm concentrations, testicular volume and sperm shape. Noticeable changes in either sperm concentration or testicular volume did not occur by irradiation of 0.3 Gy. Sperm concentrations were markedly changed with 1.0 Gy. Changes in sperm concentrations and testicular volume after X-ray irradiation at the dose-rate of 0.32 Gy/min showed that killing effects of X-ray are apparently higher than those of gamma-ray. When the incidence of abnormal head shapes of sperm was examined in monkeys with chronic gamma-ray irradiation, the highest incidence of abnormality was 1.5-1.8% at 0.25-0.50 Gy. The incidence of sperm abnormality in monkeys was comparable to that in hamsters; however, it was markedly higher in mice than monkeys. (Namekawa, K)

  18. Flexible brain network reconfiguration supporting inhibitory control.

    Science.gov (United States)

    Spielberg, Jeffrey M; Miller, Gregory A; Heller, Wendy; Banich, Marie T

    2015-08-11

    The ability to inhibit distracting stimuli from interfering with goal-directed behavior is crucial for success in most spheres of life. Despite an abundance of studies examining regional brain activation, knowledge of the brain networks involved in inhibitory control remains quite limited. To address this critical gap, we applied graph theory tools to functional magnetic resonance imaging data collected while a large sample of adults (n = 101) performed a color-word Stroop task. Higher demand for inhibitory control was associated with restructuring of the global network into a configuration that was more optimized for specialized processing (functional segregation), more efficient at communicating the output of such processing across the network (functional integration), and more resilient to potential interruption (resilience). In addition, there were regional changes with right inferior frontal sulcus and right anterior insula occupying more central positions as network hubs, and dorsal anterior cingulate cortex becoming more tightly coupled with its regional subnetwork. Given the crucial role of inhibitory control in goal-directed behavior, present findings identifying functional network organization supporting inhibitory control have the potential to provide additional insights into how inhibitory control may break down in a wide variety of individuals with neurological or psychiatric difficulties.

  19. Can human eyes prevent perceptual narrowing for monkey faces in human infants?

    Science.gov (United States)

    Damon, Fabrice; Bayet, Laurie; Quinn, Paul C; Hillairet de Boisferon, Anne; Méary, David; Dupierrix, Eve; Lee, Kang; Pascalis, Olivier

    2015-07-01

    Perceptual narrowing has been observed in human infants for monkey faces: 6-month-olds can discriminate between them, whereas older infants from 9 months of age display difficulty discriminating between them. The difficulty infants from 9 months have processing monkey faces has not been clearly identified. It could be due to the structural characteristics of monkey faces, particularly the key facial features that differ from human faces. The current study aimed to investigate whether the information conveyed by the eyes is of importance. We examined whether the presence of Caucasian human eyes in monkey faces allows recognition to be maintained in 6-month-olds and facilitates recognition in 9- and 12-month-olds. Our results revealed that the presence of human eyes in monkey faces maintains recognition for those faces at 6 months of age and partially facilitates recognition of those faces at 9 months of age, but not at 12 months of age. The findings are interpreted in the context of perceptual narrowing and suggest that the attenuation of processing of other-species faces is not reversed by the presence of human eyes. © 2015 Wiley Periodicals, Inc.

  20. Selection and Pairing of ’Normal’ Rhesus Monkeys (Macaca mulatta) for Research.

    Science.gov (United States)

    1978-11-08

    week intervals. Fecal bacteriological cultures did not detect any Salmonella or Shigella car- riers in the population. The male monkeys ranged in age...1Special Roert 78-6 LVEL•$ SELECTION AND PAIRING OF "NORMAL" RHESUS MONKEYS (Macaca mulatto) FOR RESEARC Matthew J. Kessler, James L. Kupper, James D...public release; distribution unlimited. SELECTION AND PAIRING OF "NORMAL" RHESUS MONKEYS (Macaca mulatta) FOR RESEARCH Matthew J. Kessler, James L

  1. An optical brain computer interface for environmental control.

    Science.gov (United States)

    Ayaz, Hasan; Shewokis, Patricia A; Bunce, Scott; Onaral, Banu

    2011-01-01

    A brain computer interface (BCI) is a system that translates neurophysiological signals detected from the brain to supply input to a computer or to control a device. Volitional control of neural activity and its real-time detection through neuroimaging modalities are key constituents of BCI systems. The purpose of this study was to develop and test a new BCI design that utilizes intention-related cognitive activity within the dorsolateral prefrontal cortex using functional near infrared (fNIR) spectroscopy. fNIR is a noninvasive, safe, portable and affordable optical technique with which to monitor hemodynamic changes, in the brain's cerebral cortex. Because of its portability and ease of use, fNIR is amenable to deployment in ecologically valid natural working environments. We integrated a control paradigm in a computerized 3D virtual environment to augment interactivity. Ten healthy participants volunteered for a two day study in which they navigated a virtual environment with keyboard inputs, but were required to use the fNIR-BCI for interaction with virtual objects. Results showed that participants consistently utilized the fNIR-BCI with an overall success rate of 84% and volitionally increased their cerebral oxygenation level to trigger actions within the virtual environment.

  2. Alkylmercurial encephalopathy in the monkey (Saimiri sciureus and Macaca Arctoides); a histopathologic and autoradiographic study

    Energy Technology Data Exchange (ETDEWEB)

    Garman, R H; Weiss, B; Evans, H L

    1975-01-01

    Histopathologic and autoradiographic studies were performed on monkeys of the genera Saimiri and Macaca after acute and chronic oral exposure to several dosage regimens of methylmercuric chloride (MeHg). Neuropathologic changes were primarily cortical, although subcortical lesions also were observed. Autoradiographic localization of /sup 203/Hg was greatest within glial cells (particularly Nissl-plump astrocytes, subependymal glia and Bergmann's glia) and mast cells. High levels of label within normal appearing large neurons (particularly those within Gasserian and dorsal root ganglia) indicate a lower susceptibility of these neurons to the toxic effects of MeHg. Blood and brain levels of mercury correlated well with the degree of neuropathologic change, but individual variations in susceptibility to intoxication also existed. (auth)

  3. Can monkeys make investments based on maximized pay-off?

    Directory of Open Access Journals (Sweden)

    Sophie Steelandt

    2011-03-01

    Full Text Available Animals can maximize benefits but it is not known if they adjust their investment according to expected pay-offs. We investigated whether monkeys can use different investment strategies in an exchange task. We tested eight capuchin monkeys (Cebus apella and thirteen macaques (Macaca fascicularis, Macaca tonkeana in an experiment where they could adapt their investment to the food amounts proposed by two different experimenters. One, the doubling partner, returned a reward that was twice the amount given by the subject, whereas the other, the fixed partner, always returned a constant amount regardless of the amount given. To maximize pay-offs, subjects should invest a maximal amount with the first partner and a minimal amount with the second. When tested with the fixed partner only, one third of monkeys learned to remove a maximal amount of food for immediate consumption before investing a minimal one. With both partners, most subjects failed to maximize pay-offs by using different decision rules with each partner' quality. A single Tonkean macaque succeeded in investing a maximal amount to one experimenter and a minimal amount to the other. The fact that only one of over 21 subjects learned to maximize benefits in adapting investment according to experimenters' quality indicates that such a task is difficult for monkeys, albeit not impossible.

  4. Mast cell density in isolated monkey lungs on exposure to cigarette smoke.

    OpenAIRE

    Walter, A; Walter, S

    1982-01-01

    The density and percentage of degranulated cells of the mast cell population were studied in the isolated lungs of 25 monkeys (Macaca radiata radiata) before and after acute exposure to cigarette smoke. In each animal one lung was used as the test lung while the other lung was used as its control. In the control lungs the total mean mast cell count was 9.5/mm2 and the proportion of degranulated cells was 9.7%. In the lungs exposed to smoke the total counts were lower (7.3/mm2) and the percent...

  5. Digital gene atlas of neonate common marmoset brain.

    Science.gov (United States)

    Shimogori, Tomomi; Abe, Ayumi; Go, Yasuhiro; Hashikawa, Tsutomu; Kishi, Noriyuki; Kikuchi, Satomi S; Kita, Yoshiaki; Niimi, Kimie; Nishibe, Hirozumi; Okuno, Misako; Saga, Kanako; Sakurai, Miyano; Sato, Masae; Serizawa, Tsuna; Suzuki, Sachie; Takahashi, Eiki; Tanaka, Mami; Tatsumoto, Shoji; Toki, Mitsuhiro; U, Mami; Wang, Yan; Windak, Karl J; Yamagishi, Haruhiko; Yamashita, Keiko; Yoda, Tomoko; Yoshida, Aya C; Yoshida, Chihiro; Yoshimoto, Takuro; Okano, Hideyuki

    2018-03-01

    Interest in the common marmoset (Callithrix jacchus) as a primate model animal has grown recently, in part due to the successful demonstration of transgenic marmosets. However, there is some debate as to the suitability of marmosets, compared to more widely used animal models, such as the macaque monkey and mouse. Especially, the usage of marmoset for animal models of human cognition and mental disorders, is still yet to be fully explored. To examine the prospects of the marmoset model for neuroscience research, the Marmoset Gene Atlas (https://gene-atlas.bminds.brain.riken.jp/) provides a whole brain gene expression atlas in the common marmoset. We employ in situ hybridization (ISH) to systematically analyze gene expression in neonate marmoset brains, which allows us to compare expression with other model animals such as mouse. We anticipate that these data will provide sufficient information to develop tools that enable us to reveal marmoset brain structure, function, cellular and molecular organization for primate brain research. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  6. Proximal and Distal Predictors of the Spider Monkey's Stress Levels in Fragmented Landscapes.

    Directory of Open Access Journals (Sweden)

    José D Ordóñez-Gómez

    Full Text Available The rapid loss, fragmentation and degradation of tropical forests threaten the survival of many animal species. However, the way in which these phenomena affect animal health has been poorly explored, thus limiting the design of appropriate conservation strategies. To address this, here we identified using linear mixed models the effect of proximal (diet, activity pattern, hunting and logging and distal (sum of the basal areas of fruiting-tree species [SBAFS], landscape forest cover and degree of forest fragmentation variables over fecal glucocorticoid metabolite (fGCM levels-hormones associated with animal health and fitness-of six groups of spider monkeys (Ateles geoffroyi inhabiting six landscapes with different spatial structures in Mexico. Proximal variables showed a stronger predictive power over fGCMs than distal. In this sense, increases in travel time, the occurrence of hunting, and reductions in rest time and fruit consumption resulted in higher fGCM levels. Regarding distal variables, increases in SBAFS were negatively related to fGCM levels, thus suggesting that food scarcity increases stress hormone levels. Nevertheless, contrary to theoretical expectations, spider monkeys living in smaller tracts of forest spent less time travelling, but the same time feeding on fruit as those in more forested areas. The lower net energy return associated with this combination of factors would explain why, contrary to theoretical expectations, increased forest cover was associated with increased levels of fGCMs in these groups. Our study shows that, at least in the short term, spider monkeys in fragmented landscapes do not always present higher levels of stress hormones compared to those inhabiting continuous forest, and the importance of preserving fruit sources and controlling hunting for reducing the levels of stress hormones in free ranging spider monkeys.

  7. jMonkeyEngine 3.0 cookbook

    CERN Document Server

    Edén, Rickard

    2014-01-01

    If you are a jMonkey developer or a Java developer who is interested to delve further into the game making process to expand your skillset and create more technical games, then this book is perfect for you.

  8. Control of a mobile robot through brain computer interface

    Directory of Open Access Journals (Sweden)

    Robinson Jimenez Moreno

    2015-07-01

    Full Text Available This paper poses a control interface to command the movement of a mobile robot according to signals captured from the user's brain. These signals are acquired and interpreted by Emotiv EPOC device, a 14-electrode type sensor which captures electroencephalographic (EEG signals with high resolution, which, in turn, are sent to a computer for processing. One brain-computer interface (BCI was developed based on the Emotiv software and SDK in order to command the mobile robot from a distance. Functionality tests are performed with the sensor to discriminate shift intentions of a user group, as well as with a fuzzy controller to hold the direction in case of concentration loss. As conclusion, it was possible to obtain an efficient system for robot movements by brain commands.

  9. Synthesis and Monkey-PET Study of (R)- and (S)-18F-Labeled 2-Arylbenzoheterocyclic Derivatives as Amyloid Probes with Distinctive in Vivo Kinetics.

    Science.gov (United States)

    Yang, Yanping; Wang, Xuedan; Yang, Hui; Fu, Hualong; Zhang, Jinming; Zhang, Xiaojun; Dai, Jiapei; Zhang, Zhiyong; Lin, Chunping; Guo, Yuzhi; Cui, Mengchao

    2016-11-07

    This study describes an effective strategy to improve pharmacokinetics of Aβ imaging agents, offering a novel class of (R)- and (S)- 18 F-labeled 2-arylbenzoheterocyclic derivatives which bear an additional chiral hydroxyl group on the side chain. These ligands displayed binding abilities toward Aβ aggregates with K i values ranging from 3.2 to 195.6 nM. Chirality-related discrepancy was observed in biodistribution, and (S)-2-phenylbenzoxazole enantiomers exhibited vastly improved brain clearance with washout ratios higher than 20. Notably, (S)-[ 18 F]28 possessed high binding potency (K i = 7.6 nM) and exceptional brain kinetics (9.46% ID/g at 2 min, brain 2min /brain 60min = 27.8) that is superior to well-established [ 18 F]AV45. The excellent pharmacokinetics and low nonspecific binding of (S)-[ 18 F]28 were testified by dynamic PET/CT scans in monkey brains. In addition, (S)-[ 18 F]28 clearly labeled Aβ plaques both in vitro and ex vivo. These results might qualify (S)-[ 18 F]28 to detect Aβ plaques with high signal-to-noise ratio.

  10. Monkey liver cytochrome P450 2C9 is involved in caffeine 7-N-demethylation to form theophylline.

    Science.gov (United States)

    Utoh, Masahiro; Murayama, Norie; Uno, Yasuhiro; Onose, Yui; Hosaka, Shinya; Fujino, Hideki; Shimizu, Makiko; Iwasaki, Kazuhide; Yamazaki, Hiroshi

    2013-12-01

    Caffeine (1,3,7-trimethylxanthine) is a phenotyping substrate for human cytochrome P450 1A2. 3-N-Demethylation of caffeine is the main human metabolic pathway, whereas monkeys extensively mediate the 7-N-demethylation of caffeine to form pharmacological active theophylline. Roles of monkey P450 enzymes in theophylline formation from caffeine were investigated using individual monkey liver microsomes and 14 recombinantly expressed monkey P450 enzymes, and the results were compared with those for human P450 enzymes. Caffeine 7-N-demethylation activity in microsomes from 20 monkey livers was not strongly inhibited by α-naphthoflavone, quinidine or ketoconazole, and was roughly correlated with diclofenac 4'-hydroxylation activities. Monkey P450 2C9 had the highest activity for caffeine 7-N-demethylation. Kinetic analysis revealed that monkey P450 2C9 had a high Vmax/Km value for caffeine 7-N-demethylation, comparable to low Km value for monkey liver microsomes. Caffeine could dock favorably with monkey P450 2C9 modeled for 7-N-demethylation and with human P450 1A2 for 3-N-demethylation. The primary metabolite theophylline was oxidized to 8-hydroxytheophylline in similar ways by liver microsomes and by recombinant P450s in both humans and monkeys. These results collectively suggest a high activity for monkey liver P450 2C9 toward caffeine 7-N-demethylation, whereas, in humans, P450 1A2-mediated caffeine 3-N-demethylation is dominant.

  11. Pre-clinical testing of a phased array ultrasound system for MRI-guided noninvasive surgery of the brain--a primate study.

    Science.gov (United States)

    Hynynen, Kullervo; McDannold, Nathan; Clement, Greg; Jolesz, Ferenc A; Zadicario, Eyal; Killiany, Ron; Moore, Tara; Rosen, Douglas

    2006-08-01

    MRI-guided and monitored focused ultrasound thermal surgery of brain through intact skull was tested in three rhesus monkeys. The aim of this study was to determine the amount of skull heating in an animal model with a head shape similar to that of a human. The ultrasound beam was generated by a 512 channel phased array system (Exablate 3000, InSightec, Haifa, Israel) that was integrated within a 1.5-T MR-scanner. The skin was pre-cooled by degassed temperature controlled water circulating between the array surface and the skin. Skull surface temperature was measured with invasive thermocouple probes. The results showed that by applying surface cooling the skin and skull surface can be protected, and that the brain surface temperature becomes the limiting factor. The MRI thermometry was shown to be useful in detecting the tissue temperature distribution next to the bone, and it should be used to monitor the brain surface temperature. The acoustic intensity values during the 20 s sonications were adequate for thermal ablation in the human brain provided that surface cooling is used.

  12. Hemorrhoids: an experimental model in monkeys

    Directory of Open Access Journals (Sweden)

    Plapler Hélio

    2006-01-01

    Full Text Available PURPOSE: Hemorrhoids are a matter of concern due to a painful outcome. We describe a simple, easy and reliable experimental model to produce hemorrhoids in monkeys. METHODS: 14 monkeys (Cebus apella were used. After general anesthesia, hemorrhoids were induced by ligation of the inferior hemorrhoidal vein, which is very alike to humans. The vein was located through a perianal incision, dissected and ligated with a 3-0 vicryl. The skin was sutured with a 4-0 catgut thread. Animals were kept in appropriate cages and evaluated daily. RESULTS: Nine days later there were hemorrhoidal piles in the anus in fifty percent (50% of the animals. Outcome was unremarkable. There was no bleeding and all animals showed no signs of pain or suffering. CONCLUSION: This is an affordable and reliable experimental model to induce hemorrhoids for experimental studies.

  13. Rod photoreceptors express GPR55 in the adult vervet monkey retina

    DEFF Research Database (Denmark)

    Bouskila, Joseph; Javadi, Pasha; Casanova, Christian

    2013-01-01

    . Yet, its formal classification is still a matter of debate. CB1R and CB2R expression patterns are well described for rodent and monkey retinas. In the monkey retina, CB1R has been localized in its neural (cone photoreceptor, horizontal, bipolar, amacrine and ganglion cells) and CB2R in glial...

  14. High-Throughput Method of Whole-Brain Sectioning, Using the Tape-Transfer Technique.

    Science.gov (United States)

    Pinskiy, Vadim; Jones, Jamie; Tolpygo, Alexander S; Franciotti, Neil; Weber, Kevin; Mitra, Partha P

    2015-01-01

    Cryostat sectioning is a popular but labor-intensive method for preparing histological brain sections. We have developed a modification of the commercially available CryoJane tape collection method that significantly improves the ease of collection and the final quality of the tissue sections. The key modification involves an array of UVLEDs to achieve uniform polymerization of the glass slide and robust adhesion between the section and slide. This report presents system components and detailed procedural steps, and provides examples of end results; that is, 20 μm mouse brain sections that have been successfully processed for routine Nissl, myelin staining, DAB histochemistry, and fluorescence. The method is also suitable for larger brains, such as rat and monkey.

  15. Species-specific calls evoke asymmetric activity in the monkey's temporal poles.

    Science.gov (United States)

    Poremba, Amy; Malloy, Megan; Saunders, Richard C; Carson, Richard E; Herscovitch, Peter; Mishkin, Mortimer

    2004-01-29

    It has often been proposed that the vocal calls of monkeys are precursors of human speech, in part because they provide critical information to other members of the species who rely on them for survival and social interactions. Both behavioural and lesion studies suggest that monkeys, like humans, use the auditory system of the left hemisphere preferentially to process vocalizations. To investigate the pattern of neural activity that might underlie this particular form of functional asymmetry in monkeys, we measured local cerebral metabolic activity while the animals listened passively to species-specific calls compared with a variety of other classes of sound. Within the superior temporal gyrus, significantly greater metabolic activity occurred on the left side than on the right, only in the region of the temporal pole and only in response to monkey calls. This functional asymmetry was absent when these regions were separated by forebrain commissurotomy, suggesting that the perception of vocalizations elicits concurrent interhemispheric interactions that focus the auditory processing within a specialized area of one hemisphere.

  16. Seven years of recording from monkey cortex with a chronically implanted multiple microelectrode

    Directory of Open Access Journals (Sweden)

    Jürgen Krüger

    2010-05-01

    Full Text Available A brush of 64 microwires was chronically implanted in the ventral premotor cortex of a macaque monkey. Contrary to common approaches, the wires were inserted from the white matter side. This approach, by avoiding mechanical pressure on the dura and pia mater during penetration, disturbed only minimally the cortical recording site. With this approach isolated potentials and multiunit activity were recorded for more than seven years in about one third of electrodes. The indirect insertion method also provided an excellent stability within each recording session, and in some cases even allowed recording from the same neurons for several years. Histological examination of the implanted brain region shows only a very marginal damage the recording area. Advantages and problems related to long-term recording are discussed.

  17. Radiation-induced chromosome aberrations in lymphocytes from man and crab-eating monkey

    International Nuclear Information System (INIS)

    Takahashi, E.; Hirai, M.; Tobari, I.; Utsugi, T.; Nakai, S.

    1982-01-01

    To obtain information on the relation between yield of chromosome aberrations and dose at low-dose levels, experiments were conducted with 5, 10, 20, 30 and 50 rad of 137 Cs γ-rays, on lymphocytes from man and crab-eating monkey (Macaca fascicularis). The dose-response relationship for dicentrics was obtained from the combined data of these low-dose experiments with those of our previous ones at high doses (100-400 rad). When the difference between observed yields and those expected from the linear-quadratic model were computed, the dose-response curve had a good fit for man, but not for the monkey. The linear regression lines between 0 and 30 rad were calculated, because the expected values of α/β for man and monkey would be about 100 and 60 rad. The human data gave a satisfactory fit to a linear model, i.e., a linear increase in aberration frequency with dose, whereas this was not so for those of the monkey. Furthermore, there was some suggestive evidence for the existence of a plateau in dicentric yields between 10 and 30 rad for the monkey and between 20 and 30 rad for human lymphocytes, but more data would be needed to verify this suggestion, particularly for human lymphocytes. (orig.)

  18. The Moral Lives of Laboratory Monkeys: Television and the Ethics of Care.

    Science.gov (United States)

    Sharp, Lesley A

    2017-06-01

    Why do lab monkeys watch TV? This essay examines the preponderance of televisions in primate housing units based in academic research laboratories. Within such labs, television and related visual media are glossed as part-and-parcel of welfare or species-specific enrichment practices intended for research monkeys, a logic that is simultaneously historically- and ontologically-based. In many research centers, television figures prominently in the two inseparable domains of a lab monkey's life: as a research tool employed during experiments, and in housing units where captive monkeys are said to enjoy watching TV during "down time." My purpose is not to determine whether monkeys do indeed enjoy, or need, television; rather, I employ visual media as a means to uncover, and decipher, the moral logic of an ethics of care directed specifically at highly sentient creatures who serve as human proxies in a range of experimental contexts. I suggest that this specialized ethics of animal care materializes Mattingly's notion of "moral laboratories" (Mattingly in Moral laboratories: family peril and the struggle for a good life, University of California Press, Berkeley, 2014), where television mediates the troublesome boundary of species difference among the simian and human subjects who cohabit laboratory worlds.

  19. Early Paradoxical Increase of Dopamine: A Neurochemical Study of Olfactory Bulb in Asymptomatic and Symptomatic MPTP Treated Monkeys

    Directory of Open Access Journals (Sweden)

    Christian Pifl

    2017-05-01

    Full Text Available Parkinson’s disease (PD is a neurodegenerative disease with both motor and non-motor manifestations. Hyposmia is one of the early non-motor symptoms, which can precede motor symptoms by several years. The relationship between hyposmia and PD remains elusive. Olfactory bulb (OB pathology shows an increased number of olfactory dopaminergic cells, protein aggregates and dysfunction of neurotransmitter systems. In this study we examined tissue levels of dopamine (DA and serotonin (5-hydroxytryptamine, 5-HT and their metabolites, of noradrenaline (NA and of the amino acid neurotransmitters aspartate, glutamate, taurine and γ-aminobutyric acid in OBs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP treated Macaca fascicularis in different stages, including monkeys who were always asymptomatic, monkeys who recovered from mild parkinsonian signs, and monkeys with stable moderate or severe parkinsonism. DA was increased compared to controls, while neither NA and 5-HT nor the amino acid neurotransmitters were significantly changed. Furthermore, DA increased before stable motor deficits appear with +51% in asymptomatic and +96% in recovered monkeys. Unchanged DA metabolites suggest a special metabolic profile of the newly formed DA neurons. Significant correlation of homovanillic acid (HVA with taurine single values within the four MPTP groups and of aspartate with taurine within the asymptomatic and recovered MPTP groups, but not within the controls suggest interactions in the OB between taurine and the DA system and taurine and the excitatory neurotransmitter triggered by MPTP. This first investigation of OB in various stages after MPTP administration suggests that the DA increase seems to be an early phenomenon, not requiring profound nigrostriatal neurodegeneration or PD symptoms.

  20. Differences in behaviour and physiology between adult surrogate-reared and mother-reared Cynomolgous monkeys (Macaca fascicularis)

    NARCIS (Netherlands)

    Luijk, I.A.F. van; Timmermans, P.J.A.; Sweep, C.G.J.; Willems, J.; Vossen, J.M.H.

    2000-01-01

    Previous studies of the effects of rearing conditions on exploratory behaviour revealed that 80% of monkeys reared in peer groups with surrogate mothers developed neophobia, whereas only 15 % of mother-reared monkeys did. Young surrogate-reared and, especially, isolated rhesus monkeys are known to