Interaction of the dorsolateral prefrontal cortex with the precuneal medial parietal cortex for the monitoring of information in working memory in the macaque monkey.

The executive control process of monitoring information in working memory depends on the mid-dorsolateral prefrontal cortical region (cytoarchitectonic areas 46 and 9/46) in interaction with the hippocampal memory system. Anatomical studies demonstrated strong connectivity between the mid-dorsolateral prefrontal cortex and the medial parietal area PGm that lies on the precuneus. Area PGm is also strongly connected with the attentional system on the lateral inferior parietal lobule (area PG) and the limbic retrosplenial/posterior cingulate region that interacts with the hippocampal memory system. Thus, in terms of anatomical connectivity, area PGm appears to be a critical node for the integration of executive control processing from the prefrontal cortex with the online attentional and memory related processing. This hypothesis was tested in macaque monkeys with the crossed unilateral lesion methodology. A unilateral lesion in the mid-dorsolateral prefrontal cortex was combined with a unilateral lesion in area PGm in the opposite hemisphere. The results demonstrated an impairment on the externally ordered working memory task that assesses the monitoring of information in working memory. Thus, the medial parietal area PGm is a critical node in mediating the functional interaction between the prefrontal region for the executive control process of monitoring information and the memory system.

Optimal blocking of the cerebral cortex for cytoarchitectonic examination: a neuronavigation-based approach.

Certain sulci of the human cerebral cortex hold consistent relationships to cytoarchitectonic areas (e.g. the primary motor cortical area 4 and the somatosensory cortical area 3 occupy the anterior and posterior banks of the central sulcus, respectively). Recent research has improved knowledge of the cortical sulci and their variability across individuals. However, other than the so-called primary sulci, understanding of the precise relationships cortical folds hold with many cytoarchitectonic areas remains elusive. To examine these relationships, the cortex must be blocked, sectioned, and histologically processed in a manner that allows the cytoarchitectonic layers to be clearly observed. The optimal strategy to view the cytoarchitecture is to block and section the cortex perpendicular to the sulcal orientation. Most cytoarchitectonic investigations of the cortex, however, have been conducted on specimens cut along a single axis (e.g. the coronal plane), which distorts the appearance of the cytoarchitectonic layers within parts of the cortical ribbon not sectioned optimally. Thus, to understand further the relationships between sulci and cytoarchitectonic areas, the cortex should be sectioned optimally to the sulci of interest. A novel approach for blocking the cortex optimally using structural magnetic resonance imaging (MRI) and surgical neuronavigation tools is presented here.

Chimpanzee histology and functional brain imaging show that the paracingulate sulcus is not human-specific.

The paracingulate sulcus -PCGS- has been considered for a long time to be specific to the human brain. Its presence/absence has been discussed in relation to interindividual variability of personality traits and cognitive abilities. Recently, a putative PCGS has been observed in chimpanzee brains. To demonstrate that this newly discovered sulcus is the homologue of the PCGS in the human brain, we analyzed cytoarchitectonic and resting-state functional magnetic resonance imaging data in chimpanzee brains which did or did not display a PCGS. The results show that the organization of the mid-cingulate cortex of the chimpanzee brain is comparable to that of the human brain, both cytoarchitectonically and in terms of functional connectivity with the lateral frontal cortex. These results demonstrate that the PCGS is not human-specific but is a shared feature of the primate brain since at least the last common ancestor to humans and great apes ~6 mya.

Frameless Stereotactic Targeting of the Cerebellar Dentate Nucleus in Nonhuman Primates: Translatable Model for the Surgical Delivery of Gene Therapy.

BACKGROUND: Stereotactic targeting techniques in nonhuman primate (NHP) models are often utilized in the preclinical investigation of new drug therapies with the goal of demonstrating accurate and reliable delivery of a therapy to the target tissue. However, targeting certain neuroanatomical structures can be challenging. The deep cerebellar nuclei, specifically the dentate nucleus, are potential stereotactic targets for the treatment of certain ataxias. Currently, there are no detailed techniques describing frameless targeting of these structures in a NHP model. A well-defined, accurate, and reliable stereotactic surgical approach to the dentate in these animal models is critical to prove the feasibility and safety of drug delivery in order to develop clinical protocols. METHODS: Frameless stereotactic neuronavigation was employed to target the bilateral dentate nuclei of the cerebellum in four healthy juvenile Cynomolgus monkeys via a suboccipital, transcerebellar approach. The precision and accuracy of the targeting were evaluated radiologically and histologically. RESULTS: Using the described surgical methodology, we were successful in hitting the target deep cerebellar nuclei seven out of eight times. CONCLUSION: Frameless stereotactic targeting of the cerebellar dentate nuclei in NHPs for future investigational drug delivery is feasible, safe, and accurate as described by this report. Potential areas for improving the technique are discussed.

Quantitative analysis of the myelin g-ratio from electron microscopy images of the macaque corpus callosum.

We provide a detailed morphometric analysis of eight transmission electron micrographs (TEMs) obtained from the corpus callosum of one cynomolgus macaque. The raw TEM images are included in the article, along with the distributions of the axon caliber and the myelin g-ratio in each image. The distributions are analyzed to determine the relationship between axon caliber and g-ratio, and compared against the aggregate metrics (myelin volume fraction, fiber volume fraction, and the aggregate g-ratio), as defined in the accompanying research article entitled 'In vivo histology of the myelin g-ratio with magnetic resonance imaging' (Stikov et al., NeuroImage, 2015).

In vivo histology of the myelin g-ratio with magnetic resonance imaging.

The myelin g-ratio, defined as the ratio between the inner and the outer diameter of the myelin sheath, is a fundamental property of white matter that can be computed from a simple formula relating the myelin volume fraction to the fiber volume fraction or the axon volume fraction. In this paper, a unique combination of magnetization transfer, diffusion imaging and histology is presented, providing a novel method for in vivo magnetic resonance imaging of the axon volume fraction and the myelin g-ratio. Our method was demonstrated in the corpus callosum of one cynomolgus macaque, and applied to obtain full-brain g-ratio maps in one healthy human subject and one multiple sclerosis patient. In the macaque, the g-ratio was relatively constant across the corpus callosum, as measured by both MRI and electron microscopy. In the human subjects, the g-ratio in multiple sclerosis lesions was higher than in normal appearing white matter, which was in turn higher than in healthy white matter. Measuring the g-ratio brings us one step closer to fully characterizing white matter non-invasively, making it possible to perform in vivo histology of the human brain during development, aging, disease and treatment.