A new open, high-resolution, multishell, diffusion-weighted imaging dataset of the living squirrel monkey.

Although very well adapted to brain study, Magnetic Resonance Imaging (MRI) remains limited by the facilities and capabilities required to acquire data, especially for non-human primates. Addressing the data gaps resulting from these limitations requires making data more accessible and open. In contempt of the regular use of Saimiri sciureus in neuroscience research, in vivo diffusion has yet to be openly available for this species. Here we built and made openly available a unique new resource consisting of a high-resolution, multishell diffusion-weighted dataset in the anesthetized Saimiri sciureus. The data were acquired on 11 individuals with an 11.7 T MRI scanner (isotropic resolution of 400 µm3). This paper presents an overview of our dataset and illustrates some of its possible use through example analyses. To assess the quality of our data, we analyzed long-range connections (whole-brain tractography), microstructure (Neurite Orientation Dispersion and Density Imaging), and axon diameter in the corpus callosum (ActiveAx). Constituting an essential new resource for primate evolution studies, all data are openly available.

Covariations between pupil diameter and supplementary eye field activity suggest a role in cognitive effort implementation.

In both human and nonhuman primates (NHP), the medial prefrontal region, defined as the supplementary eye field (SEF), can indirectly influence behavior selection through modulation of the primary selection process in the oculomotor structures. To perform this oculomotor control, SEF integrates multiple cognitive signals such as attention, memory, reward, and error. As changes in pupil responses can assess these cognitive efforts, a better understanding of the precise dynamics by which pupil diameter and medial prefrontal cortex activity interact requires thorough investigations before, during, and after changes in pupil diameter. We tested whether SEF activity is related to pupil dynamics during a mixed pro/antisaccade oculomotor task in 2 macaque monkeys. We used functional ultrasound (fUS) imaging to examine temporal changes in brain activity at the 0.1-s time scale and 0.1-mm spatial resolution concerning behavioral performance and pupil dynamics. By combining the pupil signals and real-time imaging of NHP during cognitive tasks, we were able to infer localized cerebral blood volume (CBV) responses within a restricted part of the dorsomedial prefrontal cortex, referred to as the SEF, an area in which antisaccade preparation activity is also recorded. Inversely, SEF neurovascular activity measured by fUS imaging was found to be a robust predictor of specific variations in pupil diameter over short and long-time scales. Furthermore, we directly manipulated pupil diameter and CBV in the SEF using reward modulations. These results bring a novel understanding of the physiological links between pupil and SEF, but it also raises questions about the role of anterior cingulate cortex (ACC), as CBV variations in the ACC seems to be negligible compared to CBV variations in the SEF.

Using the Blind Spot to Investigate Trans-Saccadic Perception.

We introduce a blind spot method to create image changes contingent on eye movements. One challenge of eye movement research is triggering display changes contingent on gaze. The eye-tracking system must capture the image of the eye, discover and track the pupil and corneal reflections to estimate the gaze position, and then transfer this data to the computer that updates the display. All of these steps introduce delays that are often difficult to predict. To avoid these issues, we describe a simple blind spot method to generate gaze contingent display manipulations without any eye-tracking system and/or display controls.

The squirrel monkey model in clinical neuroscience.

Clinical neuroscience research relying on animal models brought valuable translational insights into the function and pathologies of the human brain. The anatomical, physiological, and behavioural similarities between humans and mammals have prompted researchers to study cerebral mechanisms at different levels to develop and test new treatments. The vast majority of biomedical research uses rodent models, which are easily manipulable and have a broadly resembling organisation to the human nervous system but cannot satisfactorily mimic some disorders. For these disorders, macaque monkeys have been used as they have a more comparable central nervous system. Still, this research has been hampered by limitations, including high costs and reduced samples. This review argues that a squirrel monkey model might bridge the gap by complementing translational research from rodents, macaque, and humans. With the advent of promising new methods such as ultrasound imaging, tool miniaturisation, and a shift towards open science, the squirrel monkey model represents a window of opportunity that will potentially fuel new translational discoveries in the diagnosis and treatment of brain pathologies.

Daily Torpor and Sleep in a Non-human Primate, the Gray Mouse Lemur (Microcebus murinus).

Daily torpor is an energy-saving process that evolved as an extension of non-rapid eye movement (NREM) sleep mechanisms. In many heterothermic species there is a relation between torpor expression and the repartition of the different behavioral states of sleep. Despite the presence of sleep during this period of hypothermia, torpor induces an accumulation of sleep debt which results in a rebound of sleep in mammals. We aimed to investigate the expression of sleep-wake rhythms and delta waves during daily torpor at various ambient temperatures in a non-human primate model, the gray mouse lemur (Microcebus murinus). Cortical activity was measured with telemetric electroencephalography (EEG) recordings in the prefrontal cortex (PFC) during the torpor episode and the next 24 h following hypothermia. Gray mouse lemurs were divided into two groups: the first group was subjected to normal ambient temperatures (25°C) whereas the second group was placed at lower ambient temperatures (10°C). Contrary to normal ambient temperatures, sleep-wake rhythms were maintained during torpor until body temperature (Tb) of the animals reached 21°C. Below this temperature, NREM and REM sleep strongly decreased or were absent whereas the EEG became isoelectric. The different states of sleep were proportional to Tbmin during prior torpor in contrast to active phases. Delta waves increased after torpor but low Tb did not induce greater delta power compared to higher temperatures. Our results showed that Tb was a determining factor for the quality and quantity of sleep. Low Tb might be inconsistent with the recovery function of sleep. Heterothermy caused a sleep debt thus there was a rebound of sleep at the beginning of euthermia to compensate for the lack of sleep.

Effects of n-3 polyunsaturated fatty acid supplementation on cognitive functions, electrocortical activity and neurogenesis in a non-human primate, the grey mouse lemur (Microcebus murinus).

Among environmental factors that may affect on brain function, some nutrients and particularly n-3 polyunsaturated fatty acids (n-3 PUFA) are required for optimal brain development. Their effects on cognitive functions, however, are still unclear, and studies in humans and rodents have yielded contradictory results. We used a non-human primate model, the grey mouse lemur, phylogenetically close to human. The aim of this study was to demonstrate the impact of n-3 PUFA supplementation on cognitive functions, neuronal activity and neurogenesis. Two groups of animals whose diet was supplemented with either fish oil (rich in n-3 PUFA) or olive oil as a control. These two groups were subjected to a visual discrimination task and to a test of anxiety in the open-field. In parallel, cortical activity was measured with telemetric ECoG recordings. Finally, adult neurogenesis was investigated ex vivo by means of immunohistochemistry. Animals supplemented with fish oil exhibited better visual discrimination performance and tended to have lower anxiety levels. Furthermore, supplementation increased the power of alpha, beta and gamma frequency bands in the EEG, which are related to various aspects of memory and decision-making. This study also provides the first evidence of the existence of adult neurogenesis process in a prosimian primate. Notably, lemurs supplemented with n-3 PUFAs for 21 months exhibited a higher number of newly born neurons in brain areas related to memory and emotions, compared to control animals. Altogether, these results point to long-term positive effects of dietary n-3 PUFAs on various functions of the primate brain. Further studies will be needed to determine a formal causal link between behavioral improvement and creation of new neurons.