Comparison of the predictive power of two models of cortico-cortical connections in primates: the distance rule model and the structural model.

Synaptic tract-tracing studies in macaques have provided a wealth of data about cortico-cortical connections that have been used to identify regularities and propose models and theories to explain cortical connectivity. The two most relevant of these models are the distance rule model (DRM) and the structural model (SM). They relate the strength and laminar pattern of cortico-cortical connections to two different factors: Euclidean distance (according to the DRM) and cortical type distance (according to the SM). If both predictive factors were correlated, the DRM and the SM would be compatible, but quite often, two cortical areas of similar cortical type are far apart from each other. In the present article, we have performed a conceptual analysis of the DRM and the SM to obtain predictions from each of the two models about strength and laminar pattern of cortico-cortical connections. We then tested the predictive power of each model with analyses of several cortico-cortical connectivity databases to check which of them provide the most accurate predictions. We conclude that the DRM and the SM capture the decrease in connection strength with increasing Euclidean and cortical type distances, respectively; but, for laminar pattern, type distance is a better predictor than Euclidean distance.

Cytology, architecture, development, and connections of the primate striatum: Hints for human pathology.

Degeneration of neurons and circuits across the striatum shows stereotyped time-course and spatial topography patterns that are distinct for Huntington's disease, Parkinson's disease, or the Tauopathies. These patterns of neurodegeneration in humans have not yet been systematically related to developmental, connectional, cellular, and chemical factors studied in human and non-human primates, that may underlie potential differences in selective vulnerability across striatal sectors. Relating primate anatomy to human pathology could provide new venues for identifying molecular, cellular, and connectional factors linked to the degeneration of striatal neurons and circuits. This review describes and summarizes several developmental, cellular, structural, and connectional features of the primate striatum in relation to patterns of neurodegeneration in the striatum of humans and of non-human primate models. We review (1) the types of neurons in the primate striatum, (2) the cyto-, myelo-, and chemoarchitecture of the primate striatum, (3) the developmental origin of the striatum in light of modern patterning studies, (4) the organization of corticostriatal projections in relation to cortical types, and (5) the topography and time-course of neuron loss, glial reaction, and protein aggregation induced by neurodegenerative diseases in humans and in non-human primate models across striatal sectors and their corresponding cortical areas. We summarize current knowledge about key aspects of primate striatal anatomy and human pathology and indicate knowledge gaps that should be addressed in future studies. We aim to identify factors for selective vulnerability to neurodegeneration of striatal neurons and circuits and obtain hints that could help elucidate striatal pathology in humans.

Evolution, development, and organization of the cortical connectome.

Hypotheses and theoretical frameworks are needed to organize and interpret the wealth of data on the organization of cortical networks in humans and animals in the light of development, evolution, and selective vulnerability to pathology. Goulas and colleagues compared several hypotheses of cortical network organization in 4 mammalian species and conclude that (1) the laminar pattern of cortico-cortical connections is better predicted by the Structural Model, which relates cytoarchitectonic differences of cortical areas to their interconnectedness, and (2) the existence of cortico-cortical connections is related to cytoarchitectonic differences and the physical distance between cortical areas. The predictions of the Structural Model can be applied to the human cortex, in which invasive studies are precluded. Goulas and colleagues advance interesting questions regarding the emergence of cortical structure and networks in development and evolution. Validated theories of cortical structure, development, and function can guide studies of cortical networks likely affected in neurodevelopmental disorders.

Serial Prefrontal Pathways Are Positioned to Balance Cognition and Emotion in Primates.

The delicate balance among primate prefrontal networks is necessary for homeostasis and behavioral flexibility. Dorsolateral prefrontal cortex (dlPFC) is associated with cognition, while the most ventromedial subgenual cingulate area 25 (A25) is associated with emotion and emotional expression. Yet A25 is weakly connected with dlPFC, and it is unknown how the two regions communicate. In rhesus monkeys of both sexes, we investigated how these functionally distinct areas may interact through pregenual anterior cingulate area 32 (A32), which is strongly connected with both. We found that dlPFC innervated the deep layers of A32, while A32 innervated all layers of A25, mostly targeting spines of excitatory neurons. Approximately 20% of A32 terminations formed synapses on inhibitory neurons in A25, notably the powerful parvalbumin inhibitory neurons in the deep layers, and the disinhibitory calretinin neurons in the superficial layers. By innervating distinct inhibitory microenvironments in laminar compartments, A32 is positioned to tune activity in columns of A25. The circuitry of the sequential pathway indicates that when dlPFC is engaged, A32 can dampen A25 output through the parvalbumin inhibitory microsystem in the deep layers of A25. A32 thus may flexibly recruit or reduce activity in A25 to maintain emotional equilibrium, a process that is disrupted in depression. Moreover, pyramidal neurons in A25 had a heightened density of NMDARs, which are the targets of novel rapid-acting antidepressants. Pharmacologic antagonism of NMDARs in patients with depression may reduce excitability in A25, mimicking the effects of the neurotypical serial pathway identified here.SIGNIFICANCE STATEMENT The anterior cingulate is a critical hub in prefrontal networks through connections with functionally distinct areas. Dorsolateral and polar prefrontal areas that are associated with complex cognition are connected with the anterior cingulate in a pattern that allows them to indirectly control downstream activity from the anterior cingulate to the subgenual cingulate, which is associated with heightened activity and negative affect in depression. This set of pathways provides a circuit mechanism for emotional regulation, with the anterior cingulate playing a balancing role for integration of cognitive and emotional processes. Disruption of these pathways may perturb network function and the ability to regulate cognitive and affective processes based on context.

Parallel trends in cortical gray and white matter architecture and connections in primates allow fine study of pathways in humans and reveal network disruptions in autism.

Noninvasive imaging and tractography methods have yielded information on broad communication networks but lack resolution to delineate intralaminar cortical and subcortical pathways in humans. An important unanswered question is whether we can use the wealth of precise information on pathways from monkeys to understand connections in humans. We addressed this question within a theoretical framework of systematic cortical variation and used identical high-resolution methods to compare the architecture of cortical gray matter and the white matter beneath, which gives rise to short- and long-distance pathways in humans and rhesus monkeys. We used the prefrontal cortex as a model system because of its key role in attention, emotions, and executive function, which are processes often affected in brain diseases. We found striking parallels and consistent trends in the gray and white matter architecture in humans and monkeys and between the architecture and actual connections mapped with neural tracers in rhesus monkeys and, by extension, in humans. Using the novel architectonic portrait as a base, we found significant changes in pathways between nearby prefrontal and distant areas in autism. Our findings reveal that a theoretical framework allows study of normal neural communication in humans at high resolution and specific disruptions in diverse psychiatric and neurodegenerative diseases.

Changes in thalamic dopamine innervation in a progressive Parkinson's disease model in monkeys.

BACKGROUND: Dopamine loss beyond the mesostriatal system might be relevant in pathogenic mechanisms and some clinical manifestations in PD. The primate thalamus is densely and heterogeneously innervated with dopaminergic axons, most of which express the dopamine transporter, as does the nigrostriatal system. We hypothesized that dopamine depletion may be present in the thalamus of the parkinsonian brain and set out to ascertain possible regional differences. METHODS: The toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine was administered to adult macaque monkeys using a slow intoxication protocol. The treated macaques were classified into 2 groups according to their motor status: nonsymptomatic and parkinsonian. Dopamine innervation was studied with immunohistochemistry for the dopamine transporter. Topographic maps of the dopamine transporter-immunoreactive axon distribution were generated and the total length and length density of these axons stereologically estimated using a 3-dimensional fractionator. RESULTS: Parkinsonian macaques exhibited lower dopamine transporter-immunoreactive axon length density than controls in mediodorsal and centromedian-parafascicular nuclei. Dopamine denervation in the mediodorsal nucleus was already noticeable in nonsymptomatic macaques and was even greater in parkinsonian macaques. Reticular nucleus dopamine transporter-immunoreactive axon length density presented an inverse pattern, increasing progressively to the maximum density seen in parkinsonian macaques. No changes were observed in ventral thalamic nuclei. Dopamine transporter-immunoreactive axon maps supported the quantitative findings. CONCLUSIONS: Changes in the dopamine innervation of various thalamic nuclei are heterogeneous and start in the premotor parkinsonian stage. These changes may be involved in some poorly understood nonmotor manifestations of PD. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Pathway mechanism for excitatory and inhibitory control in working memory.

Humans engage in many daily activities that rely on working memory, the ability to hold and sequence information temporarily to accomplish a task. We focus on the process of working memory, based on circuit mechanisms for attending to relevant signals and suppressing irrelevant stimuli. We discuss that connections critically depend on the systematic variation in laminar structure across all cortical systems. Laminar structure is used to group areas into types regardless of their placement in the cortex, ranging from low-type agranular areas that lack layer IV to high-type areas that have six well-delineated layers. Connections vary in laminar distribution and strength based on the difference in type between linked areas, according to the "structural model" (Barbas H, Rempel-Clower N. Cereb Cortex 7: 635-646, 1997). The many possible pathways thus vary systematically by laminar distribution and strength, and they interface with excitatory neurons to select relevant stimuli and with functionally distinct inhibitory neurons that suppress activity at the site of termination. Using prefrontal pathways, we discuss how systematic architectonic variation gives rise to diverse pathways that can be recruited, along with amygdalar and hippocampal pathways that provide sensory, affective, and contextual information. The prefrontal cortex is also connected with thalamic nuclei that receive the output of the basal ganglia and cerebellum, which may facilitate fast sequencing of information. The complement of connections and their interface with distinct inhibitory neurons allows dynamic recruitment of areas and shifts in cortical rhythms to meet rapidly changing demands of sequential components of working memory tasks.

Area 4 has layer IV in adult primates.

There are opposing views about the status of layer IV in the primary motor cortex (area 4). Cajal described a layer IV in area 4 of adult humans. In contrast, Brodmann found layer IV in developmental but not in adult primates and called area 4 'agranular'. We addressed this issue in rhesus monkeys using the neural marker SMI-32, which labels neurons in lower layer III and upper layer V, but not in layer IV. SMI-32 delineated a central unlabeled cortical stripe in area 4 that corresponds to layer IV, which was populated with small interneurons also found in layer IV in 'granular' areas (such as area 46). We distinguished layer IV interneurons from projection neurons in the layers above and below using cellular criteria. The commonly used term 'agranular' for area 4 is also used for the phylogenetically ancient limbic cortices, confusing areas that differ markedly in laminar structure. This issue pertains to the systematic variation in the architecture across cortices, traced from limbic cortices through areas with increasingly more elaborate laminar structure. The principle of systematic variation can be used to predict laminar patterns of connections across cortical systems. This principle places area 4 and agranular anterior cingulate cortices at opposite poles of the graded laminar differentiation of motor cortices. The status of layer IV in area 4 thus pertains to core organisational features of the cortex, its connections and evolution.

Hyperphosphorylated tau in Alzheimer's disease disseminates along pathways predicted by the Structural Model for Cortico-cortical Connections.

In Alzheimer´s disease (AD), hyperphosphorylated tau spreads along the cerebral cortex in a stereotypical pattern that parallels cognitive deterioration. Tau seems to spread transsynaptically along cortico-cotical pathways that, according to synaptic tract-tracing studies in nonhuman primates, have specific laminar patterns related to the cortical type of the connected areas. This relation is described in the Structural Model. In the present article, we study the laminar distribution of hyperphosphorylated tau, labeled with the antibody AT8, along temporal cortical types in postmortem human brains with different AD stages to test the predictions of the Structural Model. Brains from donors without dementia had scant AT8-immunorreactive (AT8-ir) neurons in allo-, meso-, and isocortical types. In early AD stages, the mesocortical dysgranular type, including part of the transentorhinal cortex, had the highest AT8 immunostaining and AT8-ir neurons density. In advanced AD stages, AT8 immunostaining increased along the isocortical types until reaching the auditory koniocortex. Regarding laminar patterns, in early AD stages there were more AT8-ir neurons in supragranular layers in each de novo involved neocortical type; in advanced AD stages, AT8-ir neurons were equally distributed in supra- and infragranular layers. These AT8-ir laminar patterns are compatible with the predictions of the Structural Model. In summary, we show that hyperphosphorylated tau initially accumulates in allo-, meso-, and isocortical types, offer a proof of concept for the validity of the Structural Model to predict synaptic pathway organization in the human cerebral cortex, and highlight the relevance of nonhuman primate tract-tracing studies to understand human neuropathology.

Cortical circuit principles predict patterns of trauma induced tauopathy in humans.

Connections in the cortex of diverse mammalian species are predicted reliably by the Structural Model for direction of pathways and signal processing (reviewed in 1,2). The model is rooted in the universal principle of cortical systematic variation in laminar structure and has been supported widely for connection patterns in animals but has not yet been tested for humans. Here, in postmortem brains of individuals neuropathologically diagnosed with chronic traumatic encephalopathy (CTE) we studied whether the hyperphosphorylated tau (p-tau) pathology parallels connection sequence in time by circuit mechanisms. CTE is a progressive p-tau pathology that begins focally in perivascular sites in sulcal depths of the neocortex (stages I-II) and later involves the medial temporal lobe (MTL) in stages III-IV. We provide novel quantitative evidence that the p-tau pathology in MTL A28 and nearby sites in CTE stage III closely follows the graded laminar patterns seen in homologous cortico-cortical connections in non-human primates. The Structural Model successfully predicted the laminar distribution of the p-tau neurofibrillary tangles and neurites and their density, based on the relative laminar (dis)similarity between the cortical origin (seed) and each connection site. The findings were validated for generalizability by a computational progression model. By contrast, the early focal perivascular pathology in the sulcal depths followed local columnar connectivity rules. These findings support the general applicability of a theoretical model to unravel the direction and progression of p-tau pathology in human neurodegeneration via a cortico-cortical mechanism. Cortical pathways converging on medial MTL help explain the progressive spread of p-tau pathology from focal cortical sites in early CTE to widespread lateral MTL areas and beyond in later disease stages.

Brainwide mesoscale functional networks revealed by focal infrared neural stimulation of the amygdala.

The primate amygdala serves to evaluate emotional content of sensory inputs and modulate emotional and social behaviors; it modulates cognitive, multisensory and autonomic circuits predominantly via the basal (BA), lateral (LA), and central (CeA) nuclei, respectively. Based on recent electrophysiological evidence suggesting mesoscale (millimeters-scale) nature of intra-amygdala functional organization, we have investigated the connectivity of these nuclei using Infrared Neural Stimulation of single mesoscale sites coupled with mapping in ultrahigh field 7T functional Magnetic Resonance Imaging (INS-fMRI). Stimulation of multiple sites within amygdala of single individuals evoked 'mesoscale functional connectivity maps', allowing comparison of BA, LA and CeA connected brainwide networks. This revealed a mesoscale nature of connected sites, complementary spatial patterns of functional connectivity, and topographic relationships of nucleus-specific connections. Our data reveal a functional architecture of systematically organized brainwide networks mediating sensory, cognitive, and autonomic influences from the amygdala.

Mapping the primate thalamus: historical perspective and modern approaches for defining nuclei.

The primate thalamus has been subdivided into multiple nuclei and nuclear groups based on cytoarchitectonic, myeloarchitectonic, connectional, histochemical, and genoarchitectonic differences. Regarding parcellation and terminology, two main schools prevailed in the twentieth century: the German and the Anglo-American Schools, which proposed rather different schemes. The German parcellation and terminology has been mostly used for the human thalamus in neurosurgery atlases; the Anglo-American parcellation and terminology is the most used in experimental research on the primate thalamus. In this article, we review the historical development of terminological and parcellation schemes for the primate thalamus over the last 200 years. We trace the technological innovations and conceptual advances in thalamic research that underlie each parcellation, from the use of magnifying lenses to contemporary genoarchitectonic stains during ontogeny. We also discuss the advantages, disadvantages, and practical use of each parcellation.

Homology of neocortical areas in rats and primates based on cortical type analysis: an update of the Hypothesis on the Dual Origin of the Neocortex.

Sixty years ago, Friedrich Sanides traced the origin of the tangential expansion of the primate neocortex to two ancestral anlagen in the allocortex of reptiles and mammals, and proposed the Hypothesis on the Dual Origin of the Neocortex. According to Sanides, paraolfactory and parahippocampal gradients of laminar elaboration expanded in evolution by addition of successive concentric rings of gradually different cortical types inside the allocortical ring. Rodents had fewer rings and primates had more rings in the inner part of the cortex. In the present article, we perform cortical type analysis of the neocortex of adult rats, Rhesus macaques, and humans to propose hypotheses on homology of cortical areas applying the principles of the Hypothesis on the Dual Origin of the Neocortex. We show that areas in the outer rings of the neocortex have comparable laminar elaboration in rats and primates, while most 6-layer eulaminate areas in the innermost rings of primate neocortex lack homologous counterparts in rats. We also represent the topological distribution of cortical types in simplified flat maps of the cerebral cortex of monotremes, rats, and primates. Finally, we propose an elaboration of the Hypothesis on the Dual Origin of the Neocortex in the context of modern studies of pallial patterning that integrates the specification of pallial sectors in development of vertebrate embryos. The updated version of the hypothesis of Sanides provides explanation for the emergence of cortical hierarchies in mammals and will guide future research in the phylogenetic origin of neocortical areas.

Stereotaxic cutting of post-mortem human brains for neuroanatomical studies.

Stereotaxis is widely used in clinical neurosurgery, neuroradiosurgery, and neuroimaging. Yet, maps of brain structures obtained from post-mortem human brains are not usually presented in known stereotaxic coordinates. Post-mortem brain data given in stereotaxic coordinates would facilitate comparisons with in vivo human neuroimages and would also facilitate intra and inter-experiment comparisons. In this article, we present a crafted instrument for stereotaxic cutting of post-mortem human brain hemispheres. The instrument consists of a transparent methacrylate plate facing a mirror, four legs, and lateral regularly spaced columns permitting the insertion of large knives in-between the columns. This instrument can be built in any laboratory to obtain human brain slabs in the stereotaxic space of Talairach and Tournoux. We explain in detail the procedure for stereotaxic cutting of human brain hemispheres in the coronal plane, as well as the basis for calculating stereotaxic coordinates of histological sections obtained following the stereotaxic cutting protocol.

Mapping the primate thalamus: systematic approach to analyze the distribution of subcortical neuromodulatory afferents.

Neuromodulatory afferents to thalamic nuclei are key for information transmission and thus play critical roles in sensory, motor, and limbic processes. Over the course of the last decades, diverse attempts have been made to map and describe subcortical neuromodulatory afferents to the primate thalamus, including axons using acetylcholine, serotonin, dopamine, noradrenaline, adrenaline, and histamine. Our group has been actively involved in this endeavor. The published descriptions on neuromodulatory afferents to the primate thalamus have been made in different laboratories and are not fully comparable due to methodological divergences (for example, fixation procedures, planes of cutting, techniques used to detect the afferents, different criteria for identification of thalamic nuclei…). Such variation affects the results obtained. Therefore, systematic methodological and analytical approaches are much needed. The present article proposes reproducible methodological and terminological frameworks for primate thalamic mapping. We suggest the use of standard stereotaxic planes to produce and present maps of the primate thalamus, as well as the use of the Anglo-American school terminology (vs. the German school terminology) for identification of thalamic nuclei. Finally, a public repository of the data collected under agreed-on frameworks would be a useful tool for looking up and comparing data on the structure and connections of primate thalamic nuclei. Important and agreed-on efforts are required to create, manage, and fund a unified and homogeneous resource of data on the primate thalamus. Likewise, a firm commitment of the institutions to preserve experimental brain material is much needed because neuroscience work with non-human primates is becoming increasingly rare, making earlier material still more valuable.

Cortical type: a conceptual tool for meaningful biological interpretation of high-throughput gene expression data in the human cerebral cortex.

The interpretation of massive high-throughput gene expression data requires computational and biological analyses to identify statistically and biologically significant differences, respectively. There are abundant sources that describe computational tools for statistical analysis of massive gene expression data but few address data analysis for biological significance. In the present article we exemplify the importance of selecting the proper biological context in the human brain for gene expression data analysis and interpretation. For this purpose, we use cortical type as conceptual tool to make predictions about gene expression in areas of the human temporal cortex. We predict that the expression of genes related to glutamatergic transmission would be higher in areas of simpler cortical type, the expression of genes related to GABAergic transmission would be higher in areas of more complex cortical type, and the expression of genes related to epigenetic regulation would be higher in areas of simpler cortical type. Then, we test these predictions with gene expression data from several regions of the human temporal cortex obtained from the Allen Human Brain Atlas. We find that the expression of several genes shows statistically significant differences in agreement with the predicted gradual expression along the laminar complexity gradient of the human cortex, suggesting that simpler cortical types may have greater glutamatergic excitability and epigenetic turnover compared to more complex types; on the other hand, complex cortical types seem to have greater GABAergic inhibitory control compared to simpler types. Our results show that cortical type is a good predictor of synaptic plasticity, epigenetic turnover, and selective vulnerability in human cortical areas. Thus, cortical type can provide a meaningful context for interpreting high-throughput gene expression data in the human cerebral cortex.

A role for intermediate radial glia in the tangential expansion of the mammalian cerebral cortex.

The cerebral cortex of large mammals undergoes massive surface area expansion and folding during development. Specific mechanisms to orchestrate the growth of the cortex in surface area rather than in thickness are likely to exist, but they have not been identified. Analyzing multiple species, we have identified a specialized type of progenitor cell that is exclusive to mammals with a folded cerebral cortex, which we named intermediate radial glia cell (IRGC). IRGCs express Pax6 but not Tbr2, have a radial fiber contacting the pial surface but not the ventricular surface, and are found in both the inner subventricular zone and outer subventricular zone (OSVZ). We find that IRGCs are massively generated in the OSVZ, thus augmenting the numbers of radial fibers. Fanning out of this expanding radial fiber scaffold promotes the tangential dispersion of radially migrating neurons, allowing for the growth in surface area of the cortical sheet. Accordingly, the tangential expansion of particular cortical regions was preceded by high proliferation in the underlying OSVZ, whereas the experimental reduction of IRGCs impaired the tangential dispersion of neurons and resulted in a smaller cortical surface. Thus, the generation of IRGCs plays a key role in the tangential expansion of the mammalian cerebral cortex.

The cortical spectrum: A robust structural continuum in primate cerebral cortex revealed by histological staining and magnetic resonance imaging.

High-level characterizations of the primate cerebral cortex sit between two extremes: on one end the cortical mantle is seen as a mosaic of structurally and functionally unique areas, and on the other it is seen as a uniform six-layered structure in which functional differences are defined solely by extrinsic connections. Neither of these extremes captures the crucial neuroanatomical finding: that the cortex exhibits systematic gradations in architectonic structure. These gradations have been shown to predict cortico-cortical connectivity, which in turn suggests powerful ways to ground connectomics in anatomical structure, and by extension cortical function. A challenge to widespread use of this concept is the labor-intensive and invasive nature of histological staining, which is the primary means of recognizing anatomical gradations. Here we show that a novel computational analysis technique can provide a coarse-grained picture of cortical variation. For each of 78 cortical areas spanning the entire cortical mantle of the rhesus macaque, we created a high dimensional set of anatomical features derived from captured images of cortical tissue stained for myelin and SMI-32. The method involved semi-automated de-noising of images, and enabled comparison of brain areas without hand-labeling of features such as layer boundaries. We applied multidimensional scaling (MDS) to the dataset to visualize similarity among cortical areas. This analysis shows a systematic variation between weakly laminated (limbic) cortices and sharply laminated (eulaminate) cortices. We call this smooth continuum the "cortical spectrum". We also show that this spectrum is visible within subsystems of the cortex: the occipital, parietal, temporal, motor, prefrontal, and insular cortices. We compared the MDS-derived spectrum with a spectrum produced using T1- and T2-weighted magnetic resonance imaging (MRI) data derived from macaque, and found close agreement of the two coarse-graining methods. This suggests that T1w/T2w data, routinely obtained in human MRI studies, can serve as an effective proxy for data derived from high-resolution histological methods. More generally, this approach shows that the cortical spectrum is robust to the specific method used to compare cortical areas, and is therefore a powerful tool to understand the principles of organization of the primate cortex.

Palmoplantar nonpustular psoriasiform dermatitis in a rhesus macaque.

A case of psoriasiform dermatitis in an adult male rhesus macaque is reported. Appearing spontaneously, the condition presented the clinical and histopathological features of human palmoplantar nonpustular psoriasis. The animal developed multiple scaly plaques on his palms and soles, as well as nail hyperkeratosis and widening of the nail root. Microscopically, the skin lesions showed epidermal hyperkeratosis with multifocal parakeratosis, neutrophil microabscesses in the stratum corneum, a loss of granule cell layer under the microabscesses, acanthosis, and elongation of the rete ridges; the superficial dermis showed a dense inflammatory infiltrate containing lymphocytes, macrophages and neutrophils, as well as dilated and tortuous blood vessels. The lesions improved for 15 days after intramuscular corticosteroid depot therapy and worsened slightly afterwards. Later, a spontaneous, progressive remission coincided with the beginning of spring and lasted until the end of summer; the skin lesions practically disappeared during this period, and the nails looked nearly normal. During the next autumn and winter only nail hyperkeratosis was present. Serum analyses showed hyperproteinaemia and hyperglobulinaemia during the outbreak phase and normal values during remission. The clinical and histopathological features of this case, as well as its evolution, are compared with the three other reported cases of psoriasiform skin lesions in nonhuman primates. To the authors' knowledge, this is the first report of a definite palmoplantar nonpustular psoriasiform dermatitis in a rhesus macaque.

The Epic of the Thalamus in Anatomical Language.

Understanding the origin of Greek and Latin words used as metaphors to label brain structures gives a unique window into how scientific and medical knowledge was produced, preserved, and transmitted through generations. The history of the term thalamus exemplifies the complex historical process that led to the current anatomical terminology. From its first mention by Galen of Pergamon in the 2nd century A.D. to its definitive and current use by Thomas Willis in 1664, the thalamus had an epical journey through 1500 years across Europe, the Middle East, and the North of Africa. The thalamus was confusingly described by Galen, in the Greek language, as a chamber to the brain ventricles. The term thalamus was transferred from Greek to Syriac through the translations of Galen's books done in Baghdad and also from Syriac to Arabic. Then, it was translated in Europe during the Middle Ages from the Arabic versions of Galen's books to Latin. Later, during the Early Renaissance, it was translated again to Latin directly from the Greek versions of Galen's books. Along this epical journey through languages, the term thalamus switched from referring to a hollow structure connected to brain ventricles to naming a solid structure at the rostral end of the brainstem. Finally, the thalamus was translated from Latin to modern languages, where it is used, until today, to name a nuclear complex of subcortical gray matter in the lateral walls of the third ventricle.