A somato-cognitive action network alternates with effector regions in motor cortex.

Motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down the precentral gyrus from foot to face representations1,2, despite evidence for concentric functional zones3 and maps of complex actions4. Here, using precision functional magnetic resonance imaging (fMRI) methods, we find that the classic homunculus is interrupted by regions with distinct connectivity, structure and function, alternating with effector-specific (foot, hand and mouth) areas. These inter-effector regions exhibit decreased cortical thickness and strong functional connectivity to each other, as well as to the cingulo-opercular network (CON), critical for action5 and physiological control6, arousal7, errors8 and pain9. This interdigitation of action control-linked and motor effector regions was verified in the three largest fMRI datasets. Macaque and pediatric (newborn, infant and child) precision fMRI suggested cross-species homologues and developmental precursors of the inter-effector system. A battery of motor and action fMRI tasks documented concentric effector somatotopies, separated by the CON-linked inter-effector regions. The inter-effectors lacked movement specificity and co-activated during action planning (coordination of hands and feet) and axial body movement (such as of the abdomen or eyebrows). These results, together with previous studies demonstrating stimulation-evoked complex actions4 and connectivity to internal organs10 such as the adrenal medulla, suggest that M1 is punctuated by a system for whole-body action planning, the somato-cognitive action network (SCAN). In M1, two parallel systems intertwine, forming an integrate-isolate pattern: effector-specific regions (foot, hand and mouth) for isolating fine motor control and the SCAN for integrating goals, physiology and body movement.

Longitudinal connections and the organization of the temporal cortex in macaques, great apes, and humans.

The temporal association cortex is considered a primate specialization and is involved in complex behaviors, with some, such as language, particularly characteristic of humans. The emergence of these behaviors has been linked to major differences in temporal lobe white matter in humans compared with monkeys. It is unknown, however, how the organization of the temporal lobe differs across several anthropoid primates. Therefore, we systematically compared the organization of the major temporal lobe white matter tracts in the human, gorilla, and chimpanzee great apes and in the macaque monkey. We show that humans and great apes, in particular the chimpanzee, exhibit an expanded and more complex occipital-temporal white matter system; additionally, in humans, the invasion of dorsal tracts into the temporal lobe provides a further specialization. We demonstrate the reorganization of different tracts along the primate evolutionary tree, including distinctive connectivity of human temporal gray matter.

Organization of parietoprefrontal and temporoprefrontal networks in the macaque.

The connectivity among architectonically defined areas of the frontal, parietal, and temporal cortex of the macaque has been extensively mapped through tract-tracing methods. To investigate the statistical organization underlying this connectivity, and identify its underlying architecture, we performed a hierarchical cluster analysis on 69 cortical areas based on their anatomically defined inputs. We identified 10 frontal, four parietal, and five temporal hierarchically related sets of areas (clusters), defined by unique sets of inputs and typically composed of anatomically contiguous areas. Across the cortex, clusters that share functional properties were linked by dominant information processing circuits in a topographically organized manner that reflects the organization of the main fiber bundles in the cortex. This led to a dorsal-ventral subdivision of the frontal cortex, where dorsal and ventral clusters showed privileged connectivity with parietal and temporal areas, respectively. Ventrally, temporofrontal circuits encode information to discriminate objects in the environment, their value, emotional properties, and functions such as memory and spatial navigation. Dorsal parietofrontal circuits encode information for selecting, generating, and monitoring appropriate actions based on visual-spatial and somatosensory information. This organization may reflect evolutionary antecedents, in which the vertebrate pallium, which is the ancestral cortex, was defined by a ventral and lateral olfactory region and a medial hippocampal region.NEW & NOTEWORTHY The study of cortical connectivity is crucial for understanding brain function and disease. We show that temporofrontal and parietofrontal networks in the macaque can be described in terms of circuits among clusters of areas that share similar inputs and functional properties. The resulting overall architecture described a dual subdivision of the frontal cortex, consistent with the main cortical fiber bundles and an evolutionary trend that underlies the organization of the cortex in the macaque.

Differences among the forelimb arteries in groups of primates and a mathematical model explanation.

BACKGROUND: Recently, some studies about primates have claimed the importance of the vessels to maintain the muscles working; in fact, the arterial supply could suggest how strenuous the muscular performance is associated to locomotor behavior. The aim of this work was to study the anatomy of the arteries of the forelimbs of different groups of primates to evidence a general arterial model in comparative terms. METHODS: We propose a biophysical explanation for the arterial pattern of the forelimbs of primates' groups. RESULTS: Three pattern of the forelimb arteries in Primates were descript and the differences were explained using mathematical formulas. CONCLUSIONS: The anatomical study about the comparative anatomy of the arteries of the forelimbs of primates provided hypothesis about the three observed models, mainly in relation to brachial artery division and the number of the palmar arches, in mathematical models' terms.

Quantitative assessment of prefrontal cortex in humans relative to nonhuman primates.

Humans have the largest cerebral cortex among primates. The question of whether association cortex, particularly prefrontal cortex (PFC), is disproportionately larger in humans compared with nonhuman primates is controversial: Some studies report that human PFC is relatively larger, whereas others report a more uniform PFC scaling. We address this controversy using MRI-derived cortical surfaces of many individual humans, chimpanzees, and macaques. We present two parcellation-based PFC delineations based on cytoarchitecture and function and show that a previously used morphological surrogate (cortex anterior to the genu of the corpus callosum) substantially underestimates PFC extent, especially in humans. We find that the proportion of cortical gray matter occupied by PFC in humans is up to 1.9-fold greater than in macaques and 1.2-fold greater than in chimpanzees. The disparity is even more prominent for the proportion of subcortical white matter underlying the PFC, which is 2.4-fold greater in humans than in macaques and 1.7-fold greater than in chimpanzees.

A case study in the functional consequences of scaling the sizes of realistic cortical models.

Neuroscience models come in a wide range of scales and specificity, from mean-field rate models to large-scale networks of spiking neurons. There are potential trade-offs between simplicity and realism, versatility and computational speed. This paper is about large-scale cortical network models, and the question we address is one of scalability: would scaling down cell density impact a network's ability to reproduce cortical dynamics and function? We investigated this problem using a previously constructed realistic model of the monkey visual cortex that is true to size. Reducing cell density gradually up to 50-fold, we studied changes in model behavior. Size reduction without parameter adjustment was catastrophic. Surprisingly, relatively minor compensation in synaptic weights guided by a theoretical algorithm restored mean firing rates and basic function such as orientation selectivity to models 10-20 times smaller than the real cortex. Not all was normal in the reduced model cortices: intracellular dynamics acquired a character different from that of real neurons, and while the ability to relay feedforward inputs remained intact, reduced models showed signs of deficiency in functions that required dynamical interaction among cortical neurons. These findings are not confined to models of the visual cortex, and modelers should be aware of potential issues that accompany size reduction. Broader implications of this study include the importance of homeostatic maintenance of firing rates, and the functional consequences of feedforward versus recurrent dynamics, ideas that may shed light on other species and on systems suffering cell loss.

The relative efficacy of the cranium and os coxa for taxonomic assessment in macaques.

OBJECTIVES: The cranium is generally considered more reliable than the postcranium for assessing primate taxonomy, although recent research suggests that pelvic shape may be equally reliable. However, little research has focused on intrageneric taxonomic discrimination. Here, we test the relative taxonomic efficacy of the cranium and os coxa for differentiating two macaque species, with and without considering sexual dimorphism. MATERIALS AND METHODS: Geometric morphometric analyses were performed on cranial and os coxa landmarks for 119 adult Macaca fascicularis, M. mulatta, and Chlorocebus pygerythrus. Among-group shape variation was examined using canonical variates analyses. Cross-validated discriminant function analysis provided rates of correct group classification. Additionally, average morphological distances were compared with neutral genetic distances. RESULTS: Macaque species were clearly differentiated, both cranially and pelvically, when sex was not considered. Males were more often correctly classified based on the os coxa, while female classification rates were high for both morphologies. Female crania and male os coxa were differentiated approximately the same as genetic distance, while male crania were more similar (convergent), and female os coxa were more divergent than expected based on genetic distance. DISCUSSION: The hypothesis that cranial and os coxal shape can be used to discriminate among macaque species was supported. The cranium was better at differentiating females, while the os coxa was better at differentiating male macaques. Hence, there is no a priori reason for preferring the cranium when assessing intragenetic taxonomic relationships, but the effects of high levels of sexual dimorphism must be corrected for to accurately assess taxonomic signatures.

What makes a long tail short? Testing Allen's rule in the toque macaques of Sri Lanka.

Allen's rule (1877) predicts ecogeographical anatomical variation in appendage proportions as a function of body temperature regulation. This phenomenon has been tested in a variety of animal species. In macaques, relative tail length (RTL) is one of the most frequently measured appendages to test Allen's rule. These studies have relied on museum specimens or the invasive and time-consuming capturing of free-ranging individuals. To augment sample size and lessen these logistical limitations, we designed and validated a novel noninvasive technique using digitalized photographs processed using LibreCAD, an open-source 2D-computer-aided design (CAD) application. This was used to generate pixelated measurements to calculate an RTL equivalent, the Tail to Trunk Index (TTI) = (tail [tail base to anterior tip] pixel count/trunk [neck to tail base] pixel count). The TTI of 259 adult free-ranging toque macaques (Macaca sinica) from 36 locations between 7 and 2,087 m above sea level (m.a.s.l.) was used in the analysis. Samples were collected from all three putative subspecies (M. s. sinica, aurifrons, and opisthomelas), at locations representing all altitudinal climatic zones where they are naturally distributed. These data were used to test whether toque macaque tail length variation across elevation follows Allen's rule, predicting that RTL decreases with increasing elevation and lower temperature. Our results strongly supported this prediction. There was also a statistically significant, negative correlation between elevation and annual average temperature. The best predictor for the TTI index was elevation. Significant subspecies differences in RTL are linked in part to their ecological and altitudinal niche separation, but overall the variation is seen as the species' adaptation to climate. The method developed for the quick morphometric assessment of relative body proportions, applicable for use on unhabituated free-ranging animals, widens the range of materials available for research studying morphological characteristics and their evolution in primates.

Neuron density fundamentally relates to architecture and connectivity of the primate cerebral cortex.

Studies of structural brain connectivity have revealed many intriguing features of complex cortical networks. To advance integrative theories of cortical organization, an understanding is required of how connectivity interrelates with other aspects of brain structure. Recent studies have suggested that interareal connectivity may be related to a variety of macroscopic as well as microscopic architectonic features of cortical areas. However, it is unclear how these features are inter-dependent and which of them most strongly and fundamentally relate to structural corticocortical connectivity. Here, we systematically investigated the relation of a range of microscopic and macroscopic architectonic features of cortical organization, namely layer III pyramidal cell soma cross section, dendritic synapse count, dendritic synapse density and dendritic tree size as well as area neuron density, to multiple properties of cortical connectivity, using a comprehensive, up-to-date structural connectome of the primate brain. Importantly, relationships were investigated by multi-variate analyses to account for the interrelations of features. Of all considered factors, the classical architectonic parameter of neuron density most strongly and consistently related to essential features of cortical connectivity (existence and laminar patterns of projections, area degree), and in conjoint analyses largely abolished effects of cellular morphological features. These results confirm neuron density as a central architectonic indicator of the primate cerebral cortex that is closely related to essential aspects of brain connectivity and is also highly indicative of further features of the architectonic organization of cortical areas, such as the considered cellular morphological measures. Our findings integrate several aspects of cortical micro- and macroscopic organization, with implications for cortical development and function.

Corresponding anatomical and coactivation architecture of the human precuneus showing similar connectivity patterns with macaques.

The precuneus (PCun) is one of the most expanded areas of the association cortex and plays an important role in integrating information from different modalities. However, whether the functional architecture of PCun is shared by humans and macaques is an open question. We used both anatomical connectivity and task-dependent coactivation patterns to parcellate the human PCun and consistently identified three subregions in the human PCun using two independent datasets. Two subregions were located in the dorsal PCun and one subregion was located in the ventral PCun. This parcellation scheme for the PCun was supported by identifying the subregion-specific networks and by functional characterization. Then, the absolute and relative gray matter volume of precuneus in human and macaque was calculated and significantly smaller absolute and relative gray matter volume in macaque was identified. Next, three macaque PCun subregions were defined based on our tractographic atlas. Finally, the whole brain anatomical connectivity patterns and connectivity fingerprints with 17 predefined homologous target brain areas were mapped for each PCun subregion and revealed that the PCun shares similar anatomical connectivity patterns in humans and macaques. The similar anatomical connectivity patterns of PCun were validated by an independent in-house dataset. Our findings demonstrated that anatomical connectivity patterns can reflect the functional architecture of the PCun in humans and that the functional architecture of the PCun is similar in humans and macaques.

Muscle Spindle Density of Lateral Rotators of the Thigh in Japanese Macaques and a Gibbon.

We examined the six small lateral rotators of the hip joint, which is one of the most flexible joints and allows kinematically complex motions of the hindlimb, to elucidate the functional differentiation among these muscles and to test the hypothesis that species-specific characteristics in hindlimb use during locomotion are reflected in the muscle spindle density and in other parameters of the deep small hip joint rotators. For these purposes, we estimated the number of muscle spindles of the superior gemellus muscle (SG), inferior gemellus muscle, quadratus femoris muscle, obturator internus muscle (OI), obturator externus muscle, and piriformis muscle in three Japanese macaques and a gibbon, using 30-µm-thick serial sections throughout each muscle length after azan staining. The numbers of muscle spindles per 10,000 muscle fibers were determined to compare inter-muscle variation. The spindle density was highest in the SG and lowest in the OI in the Japanese macaques, suggesting that the SG, which is attached to the tendon of the OI, functions as a kinesiological monitor of the OI. On the other hand, SG the was missing in the gibbon, and the OI in the gibbon contained more spindles than that in the Japanese macaques. This suggests that the SG and the OI fused into one muscle in the gibbon. We postulate that the relative importance of the deep small hip rotator muscles differs between the Japanese macaques and gibbon and that the gibbon's muscles are less differentiated in terms of the spindle density, probably because this brachiating species uses its hindlimbs less frequently.

Critique of Pure Marmoset.

The common marmoset, a New World (platyrrhine) monkey, is currently being fast-tracked as a non-human primate model species, especially for genetic modification but also as a general-purpose model for research on the brain and behavior bearing on the human condition. Compared to the currently dominant primate model, the catarrhine macaque monkey, marmosets are notable for certain evolutionary specializations, including their propensity for twin births, their very small size (a result of phyletic dwarfism), and features related to their small size (rapid development and relatively short lifespan), which result in these animals yielding experimental results more rapidly and at lower cost. Macaques, however, have their own advantages. Importantly, macaques are more closely related to humans (which are also catarrhine primates) than are marmosets, sharing approximately 20 million more years of common descent, and are demonstrably more similar to humans in a variety of genomic, molecular, and neurobiological characteristics. Furthermore, the very specializations of marmosets that make them attractive as experimental subjects, such as their rapid development and short lifespan, are ways in which marmosets differ from humans and in which macaques more closely resemble humans. These facts warrant careful consideration of the trade-offs between convenience and cost, on the one hand, and biological realism, on the other, in choosing between non-human primate models of human biology. Notwithstanding the advantages marmosets offer as models, prudence requires continued commitment to research on macaques and other primate species.

A Study of Selected Physicomechanical and Histological Parameters of Hair Originating from Three Primate Species.

The aim of this study was to determine selected characteristics of hair originating from adult females of three primate species: lar gibbon, crested black macaque and common chimpanzee. The research material consisted of 300 hairs collected from the top of the head. The analysis included the length, diameter, strength, breaking load, elongation and cross-section area of the hairs, and the hair index. Additionally, the scale number per 1 mm of hair length was determined using scanning electron microscope images. Lar gibbon hairs were the thinnest and the longest, while common chimpanzee hairs were the thickest and the shortest, and concurrently the least resistant. Hairs from various primate species differ in terms of their morphological structure and histological features and thus can be used for differentiation and identification of species.

Quantitative Anatomical Evidence for a Dorsoventral and Rostrocaudal Segregation within the Nonhuman Primate Frontal Cortex.

The intrinsic white matter connections of the frontal cortex are highly complex, and the organization of these connections is not fully understood. Quantitative graph-theoretical methods, which are not solely reliant on human observation and interpretation, can be powerful tools for describing the organizing network principles of frontal cortex. Here, we examined the network structure of frontal cortical subregions by applying graph-theoretical community detection analyses to a graph of frontal cortex compiled from over 400+ macaque white-matter tracing studies. We find evidence that the lateral frontal cortex can be partitioned into distinct modules roughly organized along the dorsoventral and rostrocaudal axis.

A population MRI brain template and analysis tools for the macaque.

The use of standard anatomical templates is common in human neuroimaging, as it facilitates data analysis and comparison across subjects and studies. For non-human primates, previous in vivo templates have lacked sufficient contrast to reliably validate known anatomical brain regions and have not provided tools for automated single-subject processing. Here we present the "National Institute of Mental Health Macaque Template", or NMT for short. The NMT is a high-resolution in vivo MRI template of the average macaque brain generated from 31 subjects, as well as a neuroimaging tool for improved data analysis and visualization. From the NMT volume, we generated maps of tissue segmentation and cortical thickness. Surface reconstructions and transformations to previously published digital brain atlases are also provided. We further provide an analysis pipeline using the NMT that automates and standardizes the time-consuming processes of brain extraction, tissue segmentation, and morphometric feature estimation for anatomical scans of individual subjects. The NMT and associated tools thus provide a common platform for precise single-subject data analysis and for characterizations of neuroimaging results across subjects and studies.

Macaque remains from the early Pliocene of the Iberian Peninsula.

Macaques dispersed out of Africa into Eurasia in the framework of a broader intercontinental faunal exchange that coincided in time with the sea level drop associated with the Messinian Salinity Crisis. They are first recorded in Europe (Italy and Spain) by the latest Miocene, being subsequently recorded all over Europe, albeit sparsely, throughout the Pliocene and Pleistocene. These fossil European macaques are attributed to several (sub)species of the extant Barbary macaque (Macaca sylvanus). In Iberia, fossil macaques are best documented by Macaca sylvanus florentina from various Early Pleistocene sites, whereas their published Pliocene record is very scarce. Here we report the oldest post-Messinian occurrence of macaques in the Iberian Peninsula, based on the description and metrical comparisons of two upper teeth (a male canine and a third molar of two different individuals) from the early Pliocene (MN14, 5.0-4.9 Ma) site of Puerto de la Cadena (Murcia, SE Spain). The male C1 is fully comparable in morphology with those of extant and fossil M. sylvanus, and larger than those of Mesopithecus. The M3, in turn, displays the typical papionin morphology that characterizes the dentally-conservative genus Macaca-thereby discounting an alternate assignment to either the extinct colobine monkey Mesopithecus or the more dentally-derived papionin Theropithecus. Dental size and proportions of the M3 further support an attribution to an extinct subspecies of M. sylvanus instead of the larger papionin Paradolichopithecus. Mostly on biochronologic grounds, the two macaque teeth from Puerto de la Cadena are here assigned to Macaca sylvanus cf. prisca, albeit tentatively, given the lack of clear-cut criteria to distinguish this subspecies from the younger Macaca sylvanus florentina. The described material represents the oldest well-dated Pliocene record of macaques in Iberia, predating the record of Paradolichopithecus by almost 1.5 million years.

A multivariate ecogeographic analysis of macaque craniodental variation.

OBJECTIVES: To infer the ecogeographic conditions that underlie the evolutionary diversification of macaques, we investigated the within- and between-species relationships of craniodental dimensions, geography, and environment in extant macaque species. We studied evolutionary processes by contrasting macroevolutionary patterns, phylogeny, and within-species associations. MATERIALS AND METHODS: Sixty-three linear measurements of the permanent dentition and skull along with data about climate, ecology (environment), and spatial geography were collected for 711 specimens of 12 macaque species and analyzed by a multivariate approach. Phylogenetic two-block partial least squares was used to identify patterns of covariance between craniodental and environmental variation. Phylogenetic reduced rank regression was employed to analyze spatial clines in morphological variation. RESULTS: Between-species associations consisted of two distinct multivariate patterns. The first represents overall craniodental size and is negatively associated with temperature and habitat, but positively with latitude. The second pattern shows an antero-posterior tooth size contrast related to diet, rainfall, and habitat productivity. After controlling for phylogeny, however, the latter dimension was diminished. Within-species analyses neither revealed significant association between morphology, environment, and geography, nor evidence of isolation by distance. DISCUSSION: We found evidence for environmental adaptation in macaque body and craniodental size, primarily driven by selection for thermoregulation. This pattern cannot be explained by the within-species pattern, indicating an evolved genetic basis for the between-species relationship. The dietary signal in relative tooth size, by contrast, can largely be explained by phylogeny. This cautions against adaptive interpretations of phenotype-environment associations when phylogeny is not explicitly modelled.

Primatologist: A modular segmentation pipeline for macaque brain morphometry.

Because they bridge the genetic gap between rodents and humans, non-human primates (NHPs) play a major role in therapy development and evaluation for neurological disorders. However, translational research success from NHPs to patients requires an accurate phenotyping of the models. In patients, magnetic resonance imaging (MRI) combined with automated segmentation methods has offered the unique opportunity to assess in vivo brain morphological changes. Meanwhile, specific challenges caused by brain size and high field contrasts make existing algorithms hard to use routinely in NHPs. To tackle this issue, we propose a complete pipeline, Primatologist, for multi-region segmentation. Tissue segmentation is based on a modular statistical model that includes random field regularization, bias correction and denoising and is optimized by expectation-maximization. To deal with the broad variety of structures with different relaxing times at 7 T, images are segmented into 17 anatomical classes, including subcortical regions. Pre-processing steps insure a good initialization of the parameters and thus the robustness of the pipeline. It is validated on 10 T2-weighted MRIs of healthy macaque brains. Classification scores are compared with those of a non-linear atlas registration, and the impact of each module on classification scores is thoroughly evaluated.

Geographic Variation of Absolute and Relative Lower Molar Sizes in the Japanese Macaque (Macaca fuscata: Primates, Mammalia).

We examined geographic variations of absolute and relative lower molar sizes (size proportions among M1, M2, and M3) in the Japanese macaque (Macaca fuscata) using skull specimens obtained from 13 locations. We compared the geographic patterns and climatic factors. The size of M1 significantly and negatively correlated to the annual and coldest month mean temperatures and precipitation for both males and females. The M2/M1 and M3/M1 scores significantly and positively correlated to the annual and coldest month mean temperatures. The geographic pattern in the size of M1 was consistent with Bergmann's rule; however, the sizes of M2 and M3 did not correlate with temperature, and were not consistent with the rule. The geographic pattern in relative molar sizes (M2/M1 and M3/M1 scores) indicated that populations living in colder climates possess a larger M1 in relation to M2 and M3. Therefore, the correlations of M1, M2/M1, and M3/M1 scores to temperature involve an increase in the size of M1 in a colder climate. In macaques, the functions of the different molars (M1, M2, and M3) do not differ (they all exhibit grinding function, unlike differentiation between carnassial and other molars in Carnivora), whereas the timing of molar eruption does. In other words, at young ages (1.5-3.5 years), M1 erupts and is in occlusion, whereas M2 and M3 do not erupt and are not used for mastication. Therefore, the geographic pattern in the relative molar sizes may be attributed to increasing survivability in harsh winter climates by increasing occlusal surface in younger animals.

Midsagittal Brain Variation among Non-Human Primates: Insights into Evolutionary Expansion of the Human Precuneus.

The precuneus is a major element of the superior parietal lobule, positioned on the medial side of the hemisphere and reaching the dorsal surface of the brain. It is a crucial functional region for visuospatial integration, visual imagery, and body coordination. Previously, we argued that the precuneus expanded in recent human evolution, based on a combination of paleontological, comparative, and intraspecific evidence from fossil and modern human endocasts as well as from human and chimpanzee brains. The longitudinal proportions of this region are a major source of anatomical variation among adult humans and, being much larger in Homo sapiens, is the main characteristic differentiating human midsagittal brain morphology from that of our closest living primate relative, the chimpanzee. In the current shape analysis, we examine precuneus variation in non-human primates through landmark-based models, to evaluate the general pattern of variability in non-human primates, and to test whether precuneus proportions are influenced by allometric effects of brain size. Results show that precuneus proportions do not covary with brain size, and that the main difference between monkeys and apes involves a vertical expansion of the frontal and occipital regions in apes. Such differences might reflect differences in brain proportions or differences in cranial architecture. In this sample, precuneus variation is apparently not influenced by phylogenetic or allometric factors, but does vary consistently within species, at least in chimpanzees and macaques. This result further supports the hypothesis that precuneus expansion in modern humans is not merely a consequence of increasing brain size or of allometric scaling, but rather represents a species-specific morphological change in our lineage.