A quantitative morphometric comparative analysis of the primate temporal lobe

Given their importance in language comprehension, the human temporal lobes and/or some of their component structures might be expected to be larger than allometric predictions for a nonhuman anthropoid brain of human size. Whole brain, T1-weighted MRI scans were collected from 44 living anthropoid primates spanning 11 species. Easyvision software (Philips Medical Systems, The Netherlands) was used to measure the volume of the entire brain, the temporal lobes, the superior temporal gyri, and the temporal lobe white matter. The surface areas of both the entire temporal lobe and the superior temporal gyrus were also measured, as was temporal cortical gyrification.Allometric regressions of temporal lobe structures on brain volume consistently showed apes and monkeys to scale along different trajectories, with the monkeys typically lying at a higher elevation than the apes. Within the temporal lobe, overall volume, surface area, and white matter volume were significantly larger in humans than predicted by the ape regression lines. The largest departure from allometry in humans was for the temporal lobe white matter volume which, in addition to being significantly larger than predicted for brain size, was also significantly larger than predicted for temporal lobe volume. Among the nonhuman primate sample, Cebus have small temporal lobes for their brain size, and Macaca and Papio have large superior temporal gyri for their brain size. The observed departures from allometry might reflect neurobiological adaptations supporting species-specific communication in both humans and old world monkeys.     

Backward signal from medial temporal lobe in neural circuit reorganization of primate inferotemporal cortex

Neuropsychological theories proposed a critical role of the interaction between the medial temporal lobe and neocortex in the formation of long-term memory for facts and events, which has often been tested by learning of a series of paired words or figures in humans. We identify neural mechanisms of this long-term memory formation process by single-unit recording and molecular biological methods in an animal model of visual pair-association task in monkeys. In our previous studies, we found a group of neurons that manifested selective responses to both of the paired associates (pair-coding neuron) in the anterior inferior temporal (IT) cortex. It provides strong evidence that single IT neurons acquire the response-selectivity through associative learning, and suggests that the reorganized neural circuits for the pair-coding neurons serve as the memory engram of the pair-association learning. In this article, we investigated further mechanisms of the neural circuit reorganization. First, we tested the role of the backward connections from the medial temporal lobe to IT cortex. lbotenic acid was injected unilaterally into the entorhinal and perirhinal cortex which provided massive backward projections ipsilaterally to IT cortex. We found that the limbic lesion disrupted the associative code of the IT neurons between the paired associates, without impairing the visual response to each stimulus. Second, we ask why the limbic-neocortical interactions are so important. We hypothesize that limbic neurons would undergo rapid modification of synaptic connectivity and provide backward signals that guide reorganization of neocortical neural circuits. We then investigated the molecular basis of such rapid synaptic modifiability by detecting the expression of immediate-early genes. We found strong expression of zif268 during the learning of a new set of paired associates, most intensively in area 36 of the perirhinal cortex. All these results with visual pair-association task support our hypothesis, and demonstrate that the ‘consolidation’ process, which was first proposed on the basis of clinico-psychological evidence, can now be examined in the primate with neurophysiolocical and molecular biological approaches.     

Anatomical brain asymmetries in New World and Old World monkeys: stages of temporal lobe development in primate evolution

Relatively large (n = 20-30) samples of formalin-fixed brain specimens from five Old and New World monkey species were examined in a study measuring anatomical temporal-lobe asymmetries. Linear measurements of the length of the Sylvian fissure were taken on each cerebral hemisphere to evaluate lateral differences related to development of auditory association cortex. The results indicate significantly greater Sylvian fissure length on the left hemisphere than on the right hemisphere in four of these species. Measurements of a different parameter on Saimiri sciureus brain specimens (length of anterior portion of the Sylvian fissure) also suggested temporal-lobe asymmetry favoring the left hemisphere. Other measurements (length of the Sylvian fissure lying posterior to the central sulcus, and dorso-ventral position of the Sylvian point) in Macaca mulatta and M. fascicularis did not reveal significant right/left-hemisphere differences. Sylvian-fissure length determined from photographs of M. mulatta hemispheres in contrast to results of direct measurements did not yield significant right/left-hemisphere asymmetry. We mention possible reasons why previous anatomical studies of brains from monkeys did not discern temporal-lobe asymmetry, and we also discuss whether or not certain of these asymmetries in monkeys foreshadowed the evolution of language-processing areas of the cerebral cortex in hominids.     

Endocrine abnormalities in human temporal lobe epilepsy

Patients with temporal lobe epilepsy secrete ACTH at higher rates and in greater amounts than normal subjects. Temporal lobectomy restores ACTH secretion to normal amounts and rates. The ACTH secretion in temporal lobe epilepsy is independent of anticonvulsant drug effect and seizure frequency. Electrical stimulation of medial temporal lobe structures in patients with temporal lobe epilepsy affected ACTH secretion in a manner consistent with the hypothesis that ACTH secretion is regulated by tonic inhibition. A defect in the excitatory and/or inhibitory components of this regulatory process appears to exist in temporal lobe epilepsy.     

Shaping of object representations in the human medial temporal lobe based on temporal regularities

Regularities are gradually represented in cortex after extensive experience [1], and yet they can influence behavior after minimal exposure [2, 3]. What kind of representations support such rapid statistical learning? The medial temporal lobe (MTL) can represent information from even a single experience [4], making it a good candidate system for assisting in initial learning about regularities. We combined anatomical segmentation of the MTL, high-resolution fMRI, and multivariate pattern analysis to identify representations of objects in cortical and hippocampal areas of human MTL, assessing how these representations were shaped by exposure to regularities. Subjects viewed a continuous visual stream containing hidden temporal relationships-pairs of objects that reliably appeared nearby in time. We compared the pattern of blood oxygen level-dependent activity evoked by each object before and after this exposure, and found that perirhinal cortex, parahippocampal cortex, subiculum, CA1, and CA2/CA3/dentate gyrus (CA2/3/DG) encoded regularities by increasing the representational similarity of their constituent objects. Most regions exhibited bidirectional associative shaping, whereas CA2/3/DG represented regularities in a forward-looking predictive manner. These findings suggest that object representations in MTL come to mirror the temporal structure of the environment, supporting rapid and incidental statistical learning.     

Midbrain activity shapes high-level visual properties in the primate temporal cortex

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Information flow and temporal coding in primate pattern vision

We perform time-resolved calculations of the information transmitted about visual patterns by neurons in primary visual and inferior temporal cortices. All measurable information is carried in an effective time-varying firing rate, obtained by averaging the neuronal response with a resolution no finer than about 25 ms in primary visual cortex and around twice that in inferior temporal cortex. We found no better way for a neuron receiving these messages to decode them than simply to count spikes for this long. Most of the information tends to be concentrated in one or, more often, two brief packets, one at the very beginning of the response and the other typically 100 ms later. The first packet is the most informative part of the message, but the second one generally contains new information. A small but significant part of the total information in the message accumulates gradually over the entire course of the response. These findings impose strong constraints on the codes used by these neurons.     

Interstitial cells in the primate gastrointestinal tract

Kit immunohistochemistry and confocal reconstructions have provided detailed 3-dimensional images of ICC networks throughout the gastrointestinal (GI) tract. Morphological criteria have been used to establish that different classes of ICC exist within the GI tract and physiological studies have shown that these classes have distinct physiological roles in GI motility. Structural studies have focused predominately on rodent models and less information is available on whether similar classes of ICC exist within the GI tracts of humans or non-human primates. Using Kit immunohistochemistry and confocal imaging, we examined the 3-dimensional structure of ICC throughout the GI tract of cynomolgus monkeys. Whole or flat mounts and cryostat sections were used to examine ICC networks in the lower esophageal sphincter (LES), stomach, small intestine and colon. Anti-histamine antibodies were used to distinguish ICC from mast cells in the lamina propria. Kit labeling identified complex networks of ICC populations throughout the non-human primate GI tract that have structural characteristics similar to that described for ICC populations in rodent models. ICC-MY formed anastomosing networks in the myenteric plexus region. ICC-IM were interposed between smooth muscle cells in the stomach and colon and were concentrated within the deep muscular plexus (ICC-DMP) of the intestine. ICC-SEP were found in septal regions of the antrum that separated circular muscle bundles. Spindle-shaped histamine⁺ mast cells were found in the lamina propria throughout the GI tract. Since similar sub-populations of ICC exist within the GI tract of primates and rodents and the use of rodents to study the functional roles of different classes of ICC is warranted.     

Laboratory animal models of temporal lobe epilepsy

Temporal lobe epilepsy is a common human disease that is difficult to treat. The pathogenesis of temporal lobe epilepsy, which holds many unresolved questions, and opportunities for creating more effective treatments and preventative strategies are reviewed herein. Laboratory animal models are essential to meet these challenges. How models are created, how they compare with each other and with the disease in human patients, and how they advance our understanding of temporal lobe epilepsy are described.     

Diversity and temporal dynamics of primate milk microbiomes

Milk is inhabited by a community of bacteria and is one of the first postnatal sources of microbial exposure for mammalian young. Bacteria in breast milk may enhance immune development, improve intestinal health, and stimulate the gut‐brain axis for infants. Variation in milk microbiome structure (e.g., operational taxonomic unit [OTU] diversity, community composition) may lead to different infant developmental outcomes. Milk microbiome structure may depend on evolutionary processes acting at the host species level and ecological processes occurring over lactation time, among others. We quantified milk microbiomes using 16S rRNA high‐throughput sequencing for nine primate species and for six primate mothers sampled over lactation. Our data set included humans (Homo sapiens, Philippines and USA) and eight nonhuman primate species living in captivity (bonobo [Pan paniscus], chimpanzee [Pan troglodytes], western lowland gorilla [Gorilla gorilla gorilla], Bornean orangutan [Pongo pygmaeus], Sumatran orangutan [Pongo abelii], rhesus macaque [Macaca mulatta], owl monkey [Aotus nancymaae]) and in the wild (mantled howler monkey [Alouatta palliata]). For a subset of the data, we paired microbiome data with nutrient and hormone assay results to quantify the effect of milk chemistry on milk microbiomes. We detected a core primate milk microbiome of seven bacterial OTUs indicating a robust relationship between these bacteria and primate species. Milk microbiomes differed among primate species with rhesus macaques, humans and mantled howler monkeys having notably distinct milk microbiomes. Gross energy in milk from protein and fat explained some of the variations in microbiome composition among species. Microbiome composition changed in a predictable manner for three primate mothers over lactation time, suggesting that different bacterial communities may be selected for as the infant ages. Our results contribute to understanding ecological and evolutionary relationships between bacteria and primate hosts, which can have applied benefits for humans and endangered primates in our care.     

Ganglioside changes associated with temporal lobe epilepsy in the human hippocampus

To understand better the molecular and cellular events associated with status epilepticus, a multifaceted analysis has begun on hippocampal tissues therapeutically removed from patients with temporal lobe epilepsy. In this first study, quantitative changes in major ganglioside species are reported, as well as the immunocytochemical localization on the ganglioside GD3 in epileptic human hippocampus. Although significant variations were found between patients, the pattern of change was consistent when compared to normal values obtained from an autopsied specimen and the literature. Total ganglioside content was reduced in epileptic hippocampi, which was attributable, in part, to pyramidal cell loss found in CA1 and CA3. In each case, the percentage of ganglioside GD3 was increased significantly, while ganglioside GD1a decreased. The former change is probably associated with reactive astrocytosis and the latter with loss of neuronal dendrites. Immunocytochemical localization revealed GD3 in the stratum radiatum and the subgranular layer of the dentate gyrus. In these areas, GD3 was present in punctate structures and astrocytes. These findings indicate that GD3 increases in selected areas of the sclerotic hippocampus and is presumably related to localized accumulation of reactive glial cells. Since gangliosides have a high affinity for calcium and localized increase in extracellular calcium could disrupt normal neuronal function, the localized increase in GD3 may not only denote reactive glial cells but may contribute directly to the altered, hyperexcitable condition of epilepsy.     

Immunoproteasome expression is induced in mesial temporal lobe epilepsy

Immunoproteasome has been associated to neurodegenerative and autoimmune diseases as a marker and regulator of inflammatory mechanisms. Its expression in the brain may occur upon neuroinflammation in different cell types and affect a variety of homeostatic and inflammatory pathways including the oxidized protein clearance and the self-antigen presentation. In the present study we investigated the immunoproteasome expression in hippocampi and cortex of patients affected by different histopathological forms of pharmaco-resistent mesial temporal lobe epilepsy. We identified a pathology-specific pattern of immunoproteasome expression, which could provide insight into the complex neuroinflammatory pathogenic components of this disease.