Genetic polymorphisms in the serotonin, dopamine and opioid pathways influence social attention in rhesus macaques (Macaca mulatta).

Behaviour has a significant heritable component; however, unpicking the variants of interest in the neural circuits and molecular pathways that underpin these has proven difficult. Here, we present a comprehensive analysis of the relationship between known and new candidate genes from identified pathways and key behaviours for survival in 109 adult rhesus macaques (Macaca mulatta). Eight genes involved in emotion were analysed for variation at a total of nine loci. Genetic data were then correlated with cognitive and observational measures of behaviour associated with wellbeing and survival using MCMC-based Bayesian GLMM in R, to account for relatedness within the macaque population. For four loci the variants genotyped were length polymorphisms (SLC6A4 5-hydroxytryptamine transporter length-polymorphic repeat (5-HTTLPR), SLC6A4 STin polymorphism, Tryptophan 5-hydroxylase 2 (TPH2) and Monoamine oxidase A (MAOA)) whilst for the other five (5-hydroxytryptamine receptor 2A (HTR2A), Dopamine Receptor D4 (DRD4), Oxytocin receptor (OXTR), Arginine vasopressin receptor 1A (AVPR1a), Opioid receptor mu(µ) 1 (OPRM1)) SNPs were analysed. STin genotype, DRD4 haplotype and OXTR haplotype were significantly associated with the cognitive and observational measures of behaviour associated with wellbeing and survival. Genotype for 5-HTTLPR, STin and AVPR1a, and haplotype for HTR2A, DRD4 and OXTR were significantly associated with the duration of behaviours including fear and anxiety. Understanding the biological underpinnings of individual variation in negative emotion (e.g., fear and anxiety), together with their impact on social behaviour (e.g., social attention including vigilance for threat) has application for managing primate populations in the wild and captivity, as well as potential translational application for understanding of the genetic basis of emotions in humans.

Factors Associated with Injury Rate and Pregnancy Success in Rhesus Macaques.

Fight injuries are a major welfare concern in group-housed rhesus macaques. This is particularly a problem in breeding groups. We investigated which factors might affect the injury rate in group-housed macaques and also looked at how the same factors might affect productivity. We analysed 10 years of health records at a breeding colony in which monkeys were kept in small breeding groups consisting of a single adult male and 2−13 females and their offspring or single-sex juvenile groups. We found that females over the age of 2.5 years in breeding groups were the most likely to be injured. We focused on these females and used generalised mixed-effect models to examine which factors affected the injury rate and their productivity (probability of getting pregnant). The biggest risk factor for injury was the introduction of a new adult male to a breeding group. However, this also produced a large increase in the proportion of females that became pregnant, suggesting that there may be a trade-off between the risk of injury and the productivity. We also found that females in large groups with a young breeding male had a very high risk of injury. We recommend keeping young breeding males (<7 years) in smaller groups.

Automated face recognition of rhesus macaques.

BACKGROUND: Rhesus macaques are widely used in biomedical research. Automated behavior monitoring can be useful in various fields (including neuroscience), as well as having applications to animal welfare but current technology lags behind that developed for other species. One difficulty facing developers is the reliable identification of individual macaques within a group especially as pair- and group-housing of macaques becomes standard. Current published methods require either implantation or wearing of a tracking device. NEW METHOD: I present face recognition, in combination with face detection, as a method to non-invasively identify individual rhesus macaques in videos. The face recognition method utilizes local-binary patterns in combination with a local discriminant classification algorithm. RESULTS: A classification accuracy of between 90 and 96% was achieved for four different groups. Group size, number of training images and challenging image conditions such as high contrast all had an impact on classification accuracy. I demonstrate that these methods can be applied in real time using standard affordable hardware and a potential application to studies of social structure. COMPARISON WITH EXISTING METHOD(S): Face recognition methods have been reported for humans and other primate species such as chimpanzees but not rhesus macaques. The classification accuracy with this method is comparable to that for chimpanzees. Face recognition has the advantage over other methods for identifying rhesus macaques such as tags and collars of being non-invasive. CONCLUSIONS: This is the first reported method for face recognition of rhesus macaques, has high classification accuracy and can be implemented in real time.

Corticospinal Inputs to Primate Motoneurons Innervating the Forelimb from Two Divisions of Primary Motor Cortex and Area 3a.

Previous anatomical work in primates has suggested that only corticospinal axons originating in caudal primary motor cortex ("new M1") and area 3a make monosynaptic cortico-motoneuronal connections with limb motoneurons. By contrast, the more rostral "old M1" is proposed to control motoneurons disynaptically via spinal interneurons. In six macaque monkeys, we examined the effects from focal stimulation within old and new M1 and area 3a on 135 antidromically identified motoneurons projecting to the upper limb. EPSPs with segmental latency shorter than 1.2 ms were classified as definitively monosynaptic; these were seen only after stimulation within new M1 or at the new M1/3a border (incidence 6.6% and 1.3%, respectively; total n = 27). However, most responses had longer latencies. Using measures of the response facilitation after a second stimulus compared with the first, and the reduction in response latency after a third stimulus compared with the first, we classified these late responses as likely mediated by either long-latency monosynaptic (n = 108) or non-monosynaptic linkages (n = 108). Both old and new M1 generated putative long-latency monosynaptic and non-monosynaptic effects; the majority of responses from area 3a were non-monosynaptic. Both types of responses from new M1 had significantly greater amplitude than those from old M1. We suggest that slowly conducting corticospinal fibers from old M1 generate weak late monosynaptic effects in motoneurons. These may represent a stage in control of primate motoneurons by the cortex intermediate between disynaptic output via an interposed interneuron seen in nonprimates and the fast direct monosynaptic connections present in new M1. SIGNIFICANCE STATEMENT: The corticospinal tract in Old World primates makes monosynaptic connections to motoneurons; previous anatomical work suggests that these connections come only from corticospinal tract (CST) neurons in the subdivision of primary motor cortex within the central sulcus ("new M1") and area 3a. Here, we show using electrophysiology that cortico-motoneuronal connections from fast conducting CST fibers are indeed made exclusively from new M1 and its border with 3a. However, we also show that all parts of M1 and 3a have cortico-motoneuronal connections over more slowly conducting CST axons, as well as exert disynaptic effects on motoneurons via interposed interneurons. Differences between old and new M1 are thus more subtle than previously thought.

Information theoretic analysis of proprioceptive encoding during finger flexion in the monkey sensorimotor system.

There is considerable debate over whether the brain codes information using neural firing rate or the fine-grained structure of spike timing. We investigated this issue in spike discharge recorded from single units in the sensorimotor cortex, deep cerebellar nuclei, and dorsal root ganglia in macaque monkeys trained to perform a finger flexion task. The task required flexion to four different displacements against two opposing torques; the eight possible conditions were randomly interleaved. We used information theory to assess coding of task condition in spike rate, discharge irregularity, and spectral power in the 15- to 25-Hz band during the period of steady holding. All three measures coded task information in all areas tested. Information coding was most often independent between irregularity and 15-25 Hz power (60% of units), moderately redundant between spike rate and irregularity (56% of units redundant), and highly redundant between spike rate and power (93%). Most simultaneously recorded unit pairs coded using the same measure independently (86%). Knowledge of two measures often provided extra information about task, compared with knowledge of only one alone. We conclude that sensorimotor systems use both rate and temporal codes to represent information about a finger movement task. As well as offering insights into neural coding, this work suggests that incorporating spike irregularity into algorithms used for brain-machine interfaces could improve decoding accuracy.

Coding of digit displacement by cell spiking and network oscillations in the monkey sensorimotor cortex.

ß-Band oscillations occur in motor and somatosensory cortices and muscle activity. Oscillations appear most strongly after movements, suggesting that they may represent or probe the limb's final sensory state. We tested this idea by training two macaque monkeys to perform a finger flexion to one of four displacements, which was then held for 2 s without visual feedback of absolute displacement. Local field potential (LFP) and single unit spiking were recorded from the rostral and caudal primary motor cortex and parietal areas 3a, 3b, 2, and 5. Information theoretic analysis determined how well unit firing rate or the power of LFP oscillations coded finger displacement. All areas encoded significant information about finger displacement after the movement into target, both in ß-band (∼20 Hz) oscillatory activity and unit firing rate. On average, the information carried by unit firing was greater (0.07 bits) and peaked earlier (0.73 s after peak velocity) than that by LFP ß-oscillations (0.05 bits and 0.95 s). However, there was considerable heterogeneity among units: some cells did not encode maximal information until midway through the holding phase. In 30% of cells, information in rate lagged information in LFP oscillations recorded at the same site. Finger displacement may be represented in the cortex in multiple ways. Coding the digit configuration immediately after a movement probably relies on nonoscillatory feedback, or efference copy. With increasing delay after movement cessation, oscillatory processing may also play a part.

Modulation and transmission of peripheral inputs in monkey cuneate and external cuneate nuclei.

Somatosensory signals undergo substantial modulation in the dorsal column nuclei. We examined transmission of signals from forelimb afferents in primate cuneate and external cuneate nuclei. In anesthetized macaque monkeys, the median, ulnar, deep radial, and superficial radial nerves were electrically stimulated at 1.5-2× motor threshold with independent Poisson trains whereas extracellular recordings were made from 317 cells. Responses to peripheral stimulation included instances of both brief facilitation and long lasting suppression. A high proportion of cells (87%) responded to stimulation of two or more peripheral nerves, suggesting a large amount of convergence. Facilitated cells showed coherence with the peripheral stimulation across a broad frequency range; coherence was especially high in cells that responded with a burst of action potentials. Cells that responded with suppression also showed significant coherence, but this fell rapidly for frequencies above 25 Hz. Similar results were seen in both the main and external cuneate. When stimulation of one nerve was conditioned by a preceding nerve stimulus, the response to the second stimulus was attenuated for around 40 ms. This occurred independently of whether the first stimulus produced an initial facilitation or suppression or whether the same or a different nerve served as a conditioning stimulus. Mechanical stimulation of a receptive field suppressed responses to a second identical mechanical stimulus over a similar timescale. We conclude that the primate cuneate nucleus is capable of transmitting temporal information about stimuli with high fidelity; stimuli interact both temporally and spatially to modulate the onward transmission of information.

Contributions of descending and ascending pathways to corticomuscular coherence in humans.

Corticomuscular coherence in the beta frequency band (15­30 Hz) has been demonstrated in both humans and monkeys, but its origin and functional role are still unclear. Phase­frequency plots produced by traditional coherence analysis are often complex. Some subjects show a clear linear phase­frequency relationship (indicative of a fixed delay) but give shorter delays than expected; others show a constant phase across frequencies. Recent evidence suggests that oscillations may be travelling around a peripheral sensorimotor loop. We recorded sensorimotor EEGs and EMGs from three intrinsic hand muscles in human subjects performing a precision grip task, and applied directed coherence (Granger causality) analysis to explore this system. Directed coherence was significant in both descending (EEG → EMG) and ascending(EMG → EEG) directions at beta frequencies. Average phase delays of 26.4 ms for the EEG → EMG direction and 29.5 ms for the EMG → EEG direction were closer to the expected conduction times for these pathways than the average delays estimated from coherence phase (7.9 ms). Subjects were sub-divided into different groups, based on the sign of the slope of the linear relation between corticomuscular coherence phase and frequency (positive, negative or zero). Analysis separated by these groups suggested that different relative magnitudes of EEG → EMG and EMG → EEG directed coherence might underlie the observed inter-individual differences in coherence phase.These results confirm the complex nature of corticomuscular coherence with contributions from both descending and ascending pathways.

Corticomuscular coherence between motor cortex, somatosensory areas and forearm muscles in the monkey.

Corticomuscular coherence has previously been reported between primary motor cortex (M1) and contralateral muscles. We examined whether such coherence could also be seen from somatosensory areas. Local field potentials (LFPs) were recorded from primary somatosensory cortex (S1; areas 3a and 2) and posterior parietal cortex (PPC; area 5) simultaneously with M1 LFP and forearm EMG activity in two monkeys during an index finger flexion task. Significant beta-band ( approximately 20 Hz) corticomuscular coherence was found in all areas investigated. Directed coherence (Granger causality) analysis was used to investigate the direction of effects. Surprisingly, the strongest beta-band directed coherence was in the direction from S1/PPC to muscle; it was much weaker in the ascending direction. Examination of the phase of directed coherence provided estimates of the time delay from cortex to muscle. Delays were longer from M1 ( approximately 62 ms for the first dorsal interosseous muscle) than from S1/PPC ( approximately 36 ms). We then looked at coherence and directed coherence between M1 and S1 for clues to this discrepancy. Directed coherence showed large beta-band effects from S1/PPC to M1, with smaller directed coherence in the reverse direction. The directed coherence phase suggested a delay of approximately 40 ms from M1 to S1. Corticomuscular coherence from S1/PPC could involve multiple pathways; the most important is probably common input from M1 to S1/PPC and muscles. If correct, this implies that somatosensory cortex receives oscillatory efference copy information from M1 about the motor command. This could allow sensory inflow to be interpreted in the light of its motor context.

Cells in somatosensory areas show synchrony with beta oscillations in monkey motor cortex.

Oscillatory synchronization between somatosensory and motor cortex has previously been reported using field potential recordings, but interpretation of such results can be confounded by volume conduction. We examined coherence between single-unit discharge in somatosensory/parietal areas and local field potential from the same area as the unit, or from the motor cortex, in two macaque monkeys trained to perform a finger movement task. There were clear coherence peaks at approximately 17.5 Hz for cells in the primary somatosensory cortex (both proprioceptive and cutaneous areas) and posterior parietal cortex (area 5). The size of coherence in all areas was comparable to previous reports analysing motor cortical cells and M1 field potentials. Many coherence phases clustered around -pi/2 radians, indicating zero lag synchronization of parietal cells with M1 oscillatory activity. These results indicate that cells in somatosensory and parietal areas have information about the presence of oscillations in the motor system. Such oscillatory coupling across the central sulcus may play an important role in sensorimotor integration of both proprioceptive and cutaneous signals.

Network oscillations and intrinsic spiking rhythmicity do not covary in monkey sensorimotor areas.

We investigated the relationship between local field potential (LFP) oscillations and intrinsic spiking rhythmicity in the sensorimotor system, because intrinsic rhythmicity has the potential to enhance network oscillations. LFPs and 918 single units were recorded from primary motor cortex (M1), primary somatosensory cortex (S1, areas 3a and 2), posterior parietal cortex (area 5) and the deep cerebellar nuclei (DCN). Some cells were antidromically identified as pyramidal tract neurons (PTNs). In each area the power of approximately 20 Hz LFP oscillations was assessed during periods of steady holding, when such oscillations have previously been shown to be maximal in M1. Oscillations were strongest in area 5 and weakest in the DCN. Using a previously developed method, the postspike distance-to-threshold trajectory was determined from the interspike interval histogram for each cell. Many cells had significant peaks, suggesting an intrinsic tendency towards rhythmic firing. Surprisingly, trajectory peaks were most common for M1 PTNs (115/146 cells) and rarest for area 5 neurons (12/82 cells). The extent of intrinsic spiking rhythmicity is not therefore simply related to the strength of 20 Hz oscillations in the sensorimotor system. These results suggest that intrinsic rhythmicity is not required for the generation and maintenance of oscillatory activity.