In vivo proton magnetic resonance spectroscopy of alcohol in rhesus monkey brain

Brain alcohol was measured in rhesus monkeys (Macaca mulatta) by proton magnetic resonance spectroscopy (MRS) following acute nasogastric alcohol administration (0.8 g/kg). Monkeys were anesthetized with ketamine and xylazine. A 1.5 T whole body imager and a 3-inch surface coil were used to acquire TE 30 and 270 ms spectra from a 7.5 cc voxel localized with a stimulated echo (STEAM) sequence. Venous blood samples were collected during spectral acquisitions for gas chromatographic determination of temporally concordant blood alcohol levels (BALs). Acute alcohol administration did not alter the resonance areas of N-acetylaspartate/N-acetyl containing compounds (NAA), choline containing compounds, or total creatine. The NAA resonance was used as an internal standard to calculate approximate brain alcohol concentrations, which averaged 27 ± 3% and 27 ± 8% of temporally concordant BALs (T₂-corrected TE 30 and TE 270 ms spectra, respectively). In addition to reconfirming results from prior studies finding incomplete detection of brain alcohol with MRS, these results demonstrate the feasibility of measuring brain alcohol in anesthetized nonhuman primates to examine relationships between alcohol exposure history and MRS-visibility of brain alcohol.     

Rhesus macaques spontaneously perceive formants in conspecific vocalizations

We provide a direct demonstration that nonhuman primates spontaneously perceive changes in formant frequencies in their own species-typical vocalizations, without training or reinforcement. Formants are vocal tract resonances leading to distinctive spectral prominences in the vocal signal, and provide the acoustic determinant of many key phonetic distinctions in human languages. We developed algorithms for manipulating formants in rhesus macaque calls. Using the resulting computer-manipulated calls in a habituation/dishabituation paradigm, with blind video scoring, we show that rhesus macaques spontaneously respond to a change in formant frequencies within the normal macaque vocal range. Lack of dishabituation to a "synthetic replica" signal demonstrates that dishabituation was not due to an artificial quality of synthetic calls, but to the formant shift itself. These results indicate that formant perception, a significant component of human voice and speech perception, is a perceptual ability shared with other primates.     

A practical approach to in vivo high-resolution diffusion tensor imaging of rhesus monkeys on a 3-T human scanner

The nonhuman primate brain study provides important supplemental means for human brain exploration since the two species share close anatomical and functional similarities. MR diffusion tensor imaging (DTI) in human brain has revealed exquisite details of brain structures especially in the brain white matter. However, most previous monkey brain DTI results lack the spatial resolution in comparison to the conventional tracing and postmortem imaging methods, especially when it is acquired in commonly available human MRI scanners of field strength of 3 T or lower. To meet the increasing demands for nonhuman primate DTI studies, we proposed an in vivo high-resolution monkey DTI acquisition protocol that is practically feasible and combined it with an improved postprocessing procedure for a 3-T human scanner. The acquisition protocol, susceptibility distortion correction method with phase reversal acquisition, and postprocessing steps were proved to be effective in our study of rhesus monkeys. Results from diffusion tensor estimations and fiber tractography at 1 x 1 x 1 mm(3) resolution were found to be comparable to previous ex vivo DTI studies with much longer acquisition times. Effects of image resolution were evaluated and it was confirmed that the partial volume effect due to the larger voxel size in low-resolution data biased the diffusion tensor estimation and produced erroneous fiber tractography. Our results suggest that in vivo high-resolution monkey brain DTI can be achieved within practical time, which allows accurate diffusion tensor estimation and fiber tractography in monkey brains, so that the complex anatomical structures within many small but important anatomic structures can be delineated.     

Acoustic features of male baboon loud calls: influences of context, age, and individuality

The acoustic structure of loud calls ("wahoos") recorded from free-ranging male baboons (Papio cynocephalus ursinus) in the Moremi Game Reserve, Botswana, was examined for differences between and within contexts, using calls given in response to predators (alarm wahoos), during male contests (contest wahoos), and when a male had become separated from the group (contact wahoos). Calls were recorded from adolescent, subadult, and adult males. In addition, male alarm calls were compared with those recorded from females. Despite their superficial acoustic similarity, the analysis revealed a number of significant differences between alarm, contest, and contact wahoos. Contest wahoos are given at a much higher rate, exhibit lower frequency characteristics, have a longer "hoo" duration, and a relatively louder "hoo" portion than alarm wahoos. Contact wahoos are acoustically similar to contest wahoos, but are given at a much lower rate. Both alarm and contest wahoos also exhibit significant differences among individuals. Some of the acoustic features that vary in relation to age and sex presumably reflect differences in body size, whereas others are possibly related to male stamina and endurance. The finding that calls serving markedly different functions constitute variants of the same general call type suggests that the vocal production in nonhuman primates is evolutionarily constrained.     

Quantitative ferumoxytol-enhanced MRI in pregnancy: A feasibility study in the nonhuman primate

ObjectivesTo assess the feasibility of ferumoxytol-enhanced MRI in pregnancy with a nonhuman primate model.Materials and methodsIn this prospective study, eleven pregnant rhesus macaques at day 98 ± 5 of gestation were divided into three groups, untreated control (UC) (n = 3), saline control (SC) (n = 4) and interleukin 1 beta (IL-1β) treated (IT) (n = 4), which were administered with either saline or IL-1β into the amniotic fluid. All animals were imaged at multiple time points before and after ferumoxytol administration (4 mg/kg). Longitudinal R2* and susceptibility of tissues were obtained using region-of-interest analysis and the longitudinal changes were assessed using linear mixed models and Student's t-test.ResultsIn fetuses, a slope of 0.3 s⁻¹/day (P = 0.008), 0.00 ppm/day (P = 0.699) and − 0.2 s⁻¹/day (P = 0.023) was observed in liver R2*, liver susceptibility, and lung R2*, respectively. In placentas, R2* and susceptibility increased immediately after ferumoxytol administration (P < 0.001) and decreased to baseline within two days. The mean change from baseline showed no significant difference between the SC group and the IT group at all scan time points. In maternal livers, R2* increased immediately after ferumoxytol administration, further increased at one-day, and then decreased but remained elevated (P < 0.001). The mean change from baseline showed no significant difference between the SC group and the IT group at all scan time points.ConclusionsThis work demonstrates the feasibility of quantitative ferumoxytol-enhanced MRI to measure dynamics of ferumoxytol delivery and washout in the placenta. Stable MRI measurements indicated no evidence of iron deposition in fetal tissues of nonhuman primates after maternal ferumoxytol exposure.     

To the application of the emission Mössbauer and positron annihilation spectroscopies for detection of carcinogens

Being the main cause of cancer, almost all chemical carcinogens are strong electrophiles, that is, they have a high affinity for the electron. We have shown that positron annihilation lifetime spectroscopy (PALS) is able to detect chemical carcinogens by their inhibition of positronium (Ps) formation in liquid media. Electrophilic carcinogens intercept thermalized track electrons, which are precursors of Ps, and as a result, when they are present Ps atom does not practically form. Available biophysical data seemingly indicate that frozen solutions model better an intracellular medium than the liquid ones. So it is reasonable to use emission Mössbauer spectroscopy (EMS) to detect chemical carcinogens, measuring the yield of ⁵⁷Fe²⁺ions formed in reactions of Auger electrons and other secondary electrons they produced with ⁵⁷Fe³⁺. These reactions are similar to the Ps formation process in the terminal part the positron track: e⁺+ e^? =>Ps. So EMS and PALS are complementary methods for detection of carcinogenic compounds.     

Fractional amplitude of low-frequency fluctuation changes in monkeys with spinal cord injury: A resting-state fMRI study

Purpose

Although functional magnetic resonance imaging (fMRI) has revealed that spinal cord injury (SCI) causes anomalous changes in task-induced brain activation, its effect during the resting state remains unclear. The aim of this study is to explore the changes of the brain resting-state function in non-human primates with unilateral SCI.

Materials and methods

Eleven adult female rhesus monkeys were subjected to resting-state fMRI: five with unilateral thoracic SCI and six healthy monkeys, to obtain the fractional amplitude of low-frequency fluctuations (fALFF) of the blood oxygenation level-dependent (BOLD) contrast signal to determine the influence of SCI on the cerebral resting-state function.

Results

The SCI-induced fALFF vary significantly in several encephalic regions, including the left cerebellum, the left thalamus, the right lateral geniculate nucleus, the right superior parietal lobule, and the posterior cingulate gyrus.

Conclusion

Analysis of the resting-state fMRI provides evidence of abnormal spontaneous brain activations in primates with SCI, which may help us understand the pathophysiologic mechanisms underlying the changes in neural plasticity in the central nervous system after SCI.     

Temporal integration in two species of Old World monkeys: blue monkeys (Cercopithecus mitis) and grey-cheeked mangabeys (Cercocebus albigena)

Changes in auditory sensitivity as a function of signal duration were studied in two species of Old World monkeys. Testing was conducted under free-field conditions with pure tones 250, 800, 1600, and 4000 Hz in frequency. Test stimuli ranged in duration from 35-2000 ms. The results showed that the temporal integration functions for the blue monkeys were similar to those reported for rhesus monkeys [T. D. Clack, J. Acoust. Soc. Am. 40, 1140-1146 (1966)], but differed significantly from those for mangabey monkeys and human subjects tested in the same apparatus, by the same procedure. Integration functions for humans and mangabeys did not differ. It was concluded that some taxonomic groups of primates exhibit temporal integration times that are much longer than those characteristic of humans, while others do not, and that interspecific differences in temporal integration are not readily related to species differences in their vocal repertoires.     

Detection and discrimination of synthetic English vowels by Old World monkeys (Cercopithecus, Macaca) and humans

Abilities to detect and discriminate ten synthetic steady-state English vowels were compared in Old World monkeys (Cercopithecus, Macaca) and humans using standard animal psychophysical procedures and positive-reinforcement operant conditioning techniques. Monkeys' detection thresholds were close to humans' for the front vowels /i-I-E-ae-E), but 10-20 dB higher for the back vowels /V-D-C-U-u/. Subjects were subsequently presented with groups of vowels to discriminate. All monkeys experienced difficulty with spectrally similar pairs such as /V-D/, /E-ae/, and /U-u/, but macaques were superior to Cercopithecus monkeys. Humans discriminated all vowels at 100% correct levels, but their increased response latencies reflected spectral similarity and correlated with higher error rates by monkeys. Varying the intensity level of the vowel stimuli had little effect on either monkey or human discrimination, except at the lowest levels tested. These qualitative similarities in monkey and human vowel discrimination suggest that some monkey species may provide useful models of human vowel processing at the sensory level.     

Anti-Nogo-A antibody treatment does not prevent cell body shrinkage in the motor cortex in adult monkeys subjected to unilateral cervical cord lesion

Background

After unilateral cervical cord lesion at the C7/C8 border interrupting the dorsolateral funiculus in adult monkeys, neutralization of Nogo-A using a specific monoclonal antibody promoted sprouting of corticospinal (CS) axons rostral and caudal to the lesion and, in parallel, improved functional recovery. In monkeys lesioned but not treated with the anti-Nogo-A antibody, the CS neurons in the contralesional primary motor cortex (M1) survived to the axotomy, but their soma shrank. Because the anti-Nogo-A treatment induces regeneration and/or sprouting of CS axons, it may improve access to neurotrophic factors. The question therefore arises as to whether anti-Nogo-A treatment prevents the soma shrinkage observed in the contralesional M1?

Results

Using the marker SMI-32, a quantitative and qualitative anatomical assessment of the pyramidal neurons in the layer V (thus including the CS cells) in M1 was performed and compared across three groups of animals: intact monkeys (n = 5); monkeys subjected to the cervical cord lesion and treated with a control antibody (n = 4); monkeys with the cervical lesion and treated with anti-Nogo-A antibody (n = 5). SMI-32 positive neurons on the side contralateral to the lesion were generally less well stained than those on the ipsilesional hemisphere, suggesting that they expressed less neurofilaments. Nevertheless, in all three groups of monkeys, the amount of SMI-32 positive neurons in both hemispheres was generally comparable, confirming the notion that most axotomized CS neurons survived. However, shrinkage of CS cell body area was observed in the contralesional hemisphere in the two groups of lesioned monkeys. The cell surface shrinkage was found to be of the same magnitude in the monkeys treated with the anti-Nogo-A antibody as in the control antibody treated monkeys.

Conclusion

The anti-Nogo-A antibody treatment did not preserve the axotomized CS cells from soma shrinkage, indicating that the anti-Nogo-A antibody treatment affects morphologically the axotomized CS neurons mainly at distal levels, especially the axon collateralization in the cervical cord, and little or not at all at the level of their soma.

     

Psychophysical correlates of contralateral efferent suppression. I. The role of the medial olivocochlear system in "central masking" in nonhuman primates

An extensive physiological literature, including experimental and clinical studies in humans, demonstrates that activation of the medial olivocochlear (MOC) efferent system, by either contralateral sound or electrical stimulation, can produce significant alterations in cochlear function and suggests a role for the MOC system in influencing the auditory behavior of binaural hearing. The present data are from psychophysical studies in nonhuman primates which seek to determine if the noted physiological changes in response to contralateral acoustic stimulation have a perceptual counterpart. Four juvenile Japanese macaques were trained to respond to the presence of 1-s sinusoids, presented to the test ear, in an operant reinforcement paradigm. Thresholds were compared for frequencies ranging from 1.0 to 4.0 kHz in quiet, with thresholds measured when continuous, two octave-band noise, centered on the test tone frequency, was presented in the contralateral ear. Contralateral noise was presented at levels of 10-60 dB above detection threshold for the test-tone frequency. While some variability was evident across subjects, both in the frequency distribution and magnitude (as a function of contralateral noise level), all subjects exhibited an increase, or suppression of thresholds in the presence of contralateral noise. On average, thresholds increased systematically with contralateral noise level, to a peak of 7 dB. In one subject, the threshold increase seen with contralateral noise was significantly reduced when the MOC was surgically sectioned on the floor of the IVth ventricle. The characteristics of the measured shifts in behavioral thresholds, in the presence of contralateral noise reported here, are qualitatively and quantitatively similar to both efferent physiological suppression effects and psychophysical central masking threshold shifts which have been reported previously. These data suggest that at least some aspects of "central masking" are efferent-mediated peripheral processes, and that the term "central masking" may be incorrect.     

Prior exposure to an attenuated <Emphasis Type="Italic">Listeria</Emphasis> vaccine does not reduce immunogenicity: pre-clinical assessment of the efficacy of a <Emphasis Type="Italic">Listeria</Emphasis>vaccine in the induction of immune responses against HIV

Background  

We have evaluated an attenuated Listeria monocytogenes (Lm) candidate vaccine vector in nonhuman primates using a delivery regimen relying solely on oral vaccination. We sought to determine the impact of prior Lm vector exposure on the development of new immune responses against HIV antigens.     

Cyto-, myelo- and chemoarchitecture of the prefrontal cortex of the <Emphasis Type="Italic">Cebus</Emphasis> monkey

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.     

Mössbauer studies and magnetic properties of Ln2SrCu2O6 compounds

Mössbauer and magnetic susceptibility measurements were used to study the magnetic properties of Ln_1.9Sr_1.1Cu₂O₆ (Ln=Pr,Nd) and La₂SrCu₂O₆ materials. These compounds were prepared by solid-state reaction and crystallize in a tetragonal structure, space group I4/mmm with two formula units per unit cell. There is only one crystallographic site for Cu atoms, which form a double layer of CuO₅ pyramids. These compounds are not superconducting, but we show, using Mössbauer spectroscopy (MS) on iron doped samples and susceptibility measurements, that the Cu planes order antiferromagnetically. The hyperfine fields on iron nuclei at 4.2 K extend from 472 kOe for La₂SrCu₂O₆ to 501 kOe for Nd_1.9Sr_1.1Cu₂O₆. The ordering temperaturesT _N are: R20, 190, and 250 K for Ln=La, Pr and Nd, respectively.     

Frequency and intensity discrimination in humans and monkeys

Frequency and intensity DLs were compared in humans and monkeys using a repeating standard "yes-no" procedure in which subjects reported frequency increments, frequency decrements, intensity increments, or intensity decrements in an ongoing train of 1.0-kHz tone bursts. There was only one experimental condition (intensity increments) in which monkey DLs (1.5-2.0 dB) overlapped those of humans (1.0-1.8 dB). For discrimination of both increments and decrements in frequency, monkey DLs (16-33 Hz) were approximately seven times larger than those of humans (2.4-4.8 Hz), and for discrimination of intensity decrements, monkey DLs (4.4-7.0 dB) were very unstable and larger than those of humans (1.0-1.8 dB). For intensity increment discrimination, humans and monkeys also exhibited similar DLs as SL was varied. However, for frequency increment discrimination, best DLs for humans occurred at a high (50 dB) SL, whereas best DLs for monkeys occurred at a moderate (30 dB) SL. Results are discussed in terms of various neural mechanisms that might be differentially engaged by humans and monkeys in performing these tasks; for example, different amounts of temporal versus rate coding in frequency discrimination, and different mechanisms for monitoring rate decreases in intensity discrimination. The implications of these data for using monkeys as models of human speech sound discrimination are also discussed.     

NMR Analysis of the Water-Soluble Fraction of Airborne Pollen Particles

The analysis of ambient organic aerosols by nuclear magnetic resonance (NMR) spectroscopy is limited because of the large number of organic compounds present at low concentrations. Here, we demonstrate the integrative analysis of NMR spectra of airborne pollen particles using reference spectra, spectral similarity metrics, principal components analysis (PCA), and a chemical mass balance model to determine the predominant types of organic compounds. Strong associations among glucose, fucose, specific amino acids, and airborne pollen particles were observed by spectral similarity metrics and PCA. Carbohydrates accounted for about 51 % of the airborne pollen particles in the spectrum followed by amino acids (42 %) and other compounds (7 %). Overall, our investigations showed that analysis of NMR spectral data of mixtures of environmental organic compounds with pattern recognition methods may generate information on the chemical characteristics of the mixture.     

Magnetic and151Eu mössbauer studies on EuTGa (T=Pd AND Pt) compounds

The compounds EuPdGa and EuPtGa show lattice volume anomaly indicating the abnormal valence state of Eu. in these compounds. Magnetization studies reveal that these compounds are magnetically ordered with a moment of 7 _B/f.u. at 5K. The Curie temperatures obtained from the low field ac susceptibility measurements are 38K for EuPdGa and 36K for EuPtGa.¹⁵¹Eu Mössbauer studies at 300K gave large negative isomer shifts (relative to SmF₃) and show a hyperfine split pattern at 4.2K in both the compounds. These results suggest that Eu is in a divalent state in EuPdGa and EuPtGa.     

Ferromagnetic ordering in alkali-metal iron antimonides: NaFe4Sb12 and KFe4Sb12

New alkali-metal compounds with the filled-skutterudite structure were synthesized and their chemical and physical properties investigated. X-ray diffraction, microprobe, and chemical analysis established the structure and the composition without defects on the cation site. Magnetization, ac susceptibility, specific heat, resistivity, and NMR or NQR demonstrated NaFe4Sb12 to be ferromagnetic below approximately 85 K and to exhibit an additional magnetic anomaly around 40 K. Band structure calculations find a large density of states at the Fermi energy and a ferromagnetic ground state. Similar behavior was observed for KFe4Sb12.