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Rationale: Glucagon-like peptide-1 (GLP-1) receptor agonists reduce alcohol consumption in rodents and non-human primates. Semaglutide is a new long-acting GLP-1 receptor agonist, widely used in the clinic against type 2 diabetes and obesity. It is also reported to reduce alcohol intake in rodents., Objectives: This study investigates the possible inhibitory effect of semaglutide on alcohol intake in alcohol-preferring African green monkeys., Methods: We performed a vehicle-controlled study on male monkeys that had demonstrated a preference for alcohol. In the monkeys selected for voluntary alcohol drinking, alcohol consumption was measured for ten days at baseline (Monday to Friday for two weeks). During this period, the monkeys had access to alcohol 4 h per day and free access to water 24 h per day. After two weeks of baseline measurements, the monkeys were randomized to semaglutide or vehicle. Each group consisted of ten monkeys, and the two groups were balanced with respect to baseline alcohol intake. Following the baseline period, the monkeys were treated with escalating doses of semaglutide (up to 0.05 mg/kg) or vehicle subcutaneously twice weekly for two weeks during which period alcohol was not available. After uptitration, the monkeys had access to alcohol 4 h daily for 20 days (Monday to Friday for 4 weeks), and alcohol consumption was measured. During this alcohol exposure period, treatment with semaglutide (0.05 mg/kg twice weekly) or vehicle continued for three weeks followed by a one-week washout period., Results: Compared to the vehicle, semaglutide significantly reduced alcohol intake. There were no signs of emetic events or changes in water intake., Conclusions: These data demonstrate for the first time the potent effect of semaglutide in reducing voluntary alcohol intake in non-human primates and further substantiate the need for clinical trials investigating the effect of semaglutide in patients with alcohol-use disorder., (© 2024. The Author(s).)

The probabilistic topography and inter-individual variability of the pituitary gland (PG) remain undetermined. The absence of a standardized reference atlas hinders research on PG volumetrics. In this study, we aimed at creating maximum probability maps for the anterior and posterior PG in young female adults. We manually delineated the anterior and posterior parts of the pituitary glands in 26 healthy subjects using high-resolution MRI T1 images. A three-step procedure and a cost function-masking approach were employed to optimize spatial normalization for the PG. We generated probabilistic atlases and maximum probability maps, which were subsequently coregistered back to the subjects' space and compared to manual delineations. Manual measurements led to a total pituitary volume of 705 ± 88 mm³, with the anterior and posterior volumes measuring 614 ± 82 mm³ and 91 ± 20 mm³, respectively. The mean relative volume difference between manual and atlas-based estimations was 1.3%. The global pituitary atlas exhibited an 80% (± 9%) overlap for the DICE index and 67% (± 11%) for the Jaccard index. Similarly, these values were 77% (± 13%) and 64% (± 14%) for the anterior pituitary atlas and 62% (± 21%) and 47% (± 17%) for the posterior PG atlas, respectively. We observed a substantial concordance and a significant correlation between the volume estimations of the manual and atlas-based methods for the global pituitary and anterior volumes. The maximum probability maps of the anterior and posterior PG lay the groundwork for automatic atlas-based segmentation methods and the standardized analysis of large PG datasets., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Patients with Anorexia Nervosa (AN) and athletes share intense physical activity and pituitary hormonal disturbances related to absolute (AN) or relative (athletes) undernutrition. Pituitary gland (PG) structure evaluations in those conditions are scarce, and did not differentiate anterior from posterior lobe. We evaluated the structure-function relationship of anterior and posterior PG in AN and athletes, and potential reversibility of this alteration in a group of weight-recovered patients (AN&#95;Rec). Manual delineation of anterior (AP) and posterior (PP) PG was performed on T1-weighted MR images in 17 women with AN, 15 women with AN&#95;Rec, 18 athletes women and 25 female controls. Anthropometric, hormonal, and psychometric parameters were explored and correlated with PG volumes. AP volume (APV) was lower in AN (448 ± 82 mm 3 ), AN&#95;Rec (505 ± 59 mm 3 ), and athletes (540 ± 101 mm 3 ) vs. Controls (615 ± 61 mm 3 , p < 0.00001, p < 0.00001 and p = 0.02, respectively); and smaller in AN vs. AN&#95;Rec (p = 0.007). PP volume did not show any differences between the groups. APV was positively correlated with weight (R = 0.36, p = 0.011) in AN, and luteinizing hormone (R = 0.35, p = 0.014) in total group. In AN, mean growth hormone (GH) was negatively correlated with global pituitary volume (R = 0.31, p = 0.031) and APV (R = 0.29, p = 0.037). Absolute and relative undernutrition led to a decreased anterior pituitary gland volume, which was reversible with weight gain, correlated with low bodyweight, and blockade of gonadal hypothalamic-pituitary axis. Intriguing inverse correlation between anterior pituitary gland volume and GH plasma level could suggests a low storage capacity of anterior pituitary gland and increased reactivity to low insulin-like growth factor type 1., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In recent decades, numerous structural brain imaging studies investigated purported morphometric changes in early (EB) and late onset blindness (LB). The results of these studies have not yielded very consistent results, neither with respect to the type, nor to the anatomical locations of the brain morphometric alterations. To better characterize the effects of blindness on brain morphometry, we performed a systematic review and an Anatomical-Likelihood-Estimation (ALE) coordinate-based-meta-analysis of 65 eligible studies on brain structural changes in EB and LB, including 890 EB, 466 LB and 1257 sighted controls. Results revealed atrophic changes throughout the whole extent of the retino-geniculo-striate system in both EB and LB, whereas changes in areas beyond the occipital lobe occurred in EB only. We discuss the nature of some of the contradictory findings with respect to the used brain imaging methodologies and characteristics of the blind populations such as the onset, duration and cause of blindness. Future studies should aim for much larger sample sizes, eventually by merging data from different brain imaging centers using the same imaging sequences, opt for multimodal structural brain imaging, and go beyond a purely structural approach by combining functional with structural connectivity network analyses., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

For blind individuals, tactile maps are useful tools to form cognitive maps through touch. However, they still experience challenges in cognitive map formation and independent navigation. Three-dimensional (3D) tactile information is thus increasingly being considered to convey enriched spatial information, but it remains unclear if it can facilitate cognitive map formation compared to traditional two-dimensional (2D) tactile information. Consequently, the present study investigated the impact of the type of sensory input (tactile 2D vs. tactile 3D vs. a visual control condition) on cognitive map formation. To do so, early blind (EB, n = 13), late blind (LB, n = 12), and sighted control (SC, n = 14) participants were tasked to learn the layouts of mazes produced with different sensory information (tactile 2D vs. tactile 3D vs. visual control) and to infer routes from memory. Results show that EB manifested stronger cognitive map formation with 3D mazes, LB performed equally well with 2D and 3D tactile mazes, and SC manifested equivalent cognitive map formation with visual and 3D tactile mazes but were negatively impacted by 2D tactile mazes. 3D tactile maps therefore have the potential to improve spatial learning for EB and newly blind individuals through a reduction of cognitive overload. Installation of 3D tactile maps in public spaces should be considered to promote universal accessibility and reduce blind individuals' wayfinding deficits related to the inaccessibility of spatial information through non-visual means., (© 2023. The Author(s).)

Among the deficits in visual processing that accompany healthy aging, the earliest originate in the retina. Moreover, sex-related differences in retinal function have been increasingly recognized. To better understand the dynamics of the retinal aging trajectory, we used the light-adapted flicker electroretinogram (ERG) to functionally assess the state of the neuroretina in a large cohort of age- and sex-matched vervet monkeys ( N = 35), aged 9 to 28 years old, with no signs of obvious ocular pathology. We primarily isolated the cone-bipolar axis by stimulating the retina with a standard intensity light flash (2.57 cd/s/m 2 ) at eight different frequencies, ranging from 5 to 40 Hz. Sex-specific changes in the voltage and temporal characteristics of the flicker waveform were found in older individuals (21-28 years-old, N = 16), when compared to younger monkeys (9-20 years-old, N = 19), across all stimulus frequencies tested. Specifically, significantly prolonged implicit times were observed in older monkeys ( p < 0.05), but a significant reduction of the amplitude of the response was only found in old male monkeys ( p < 0.05). These changes might reflect ongoing degenerative processes targeting the retinal circuitry and the cone subsystem in particular. Altogether, our findings corroborate the existing literature in humans and other species, where aging detrimentally affects photopic retinal responses, and draw attention to the potential contribution of different hormonal environments.

Fetal alcohol spectrum disorder (FASD) is a chronic debilitating condition resulting in behavioral and intellectual impairments and is considered the most prevalent form of preventable mental retardation in the industrialized world. We previously reported that 2-year-old offspring of vervet monkey ( Chlorocebus sabeus ) dams drinking, on average, 2.3 ± 0.49 g ethanol per Kg maternal body weight 4 days per week during the last third of pregnancy had significantly lower numbers of CA1 (-51.6%), CA2 (-51.2%) and CA3 (-42.8%) hippocampal neurons, as compared to age-matched sucrose controls. Fetal alcohol-exposed (FAE) offspring also showed significantly lower volumes for these structures at 2 years of age. In the present study, we examined these same parameters in 12 FAE offspring with a similar average but a larger range of ethanol exposures (1.01-2.98 g/Kg/day; total ethanol exposure 24-158 g/Kg). Design-based stereology was performed on cresyl violet-stained and doublecortin (DCX)-immunostained sections of the hippocampus. We report here significant neuronal deficits in the hippocampus with a significant negative correlation between daily dose and neuronal population in CA1 ( r 2 = 0.486), CA2 ( r 2 = 0.492), and CA3 ( r 2 = 0.469). There were also significant correlations between DCX population in the dentate gyrus and daily dose ( r 2 = 0.560). Both correlations were consistent with linear dose-response models. This study illustrates that neuroanatomical sequelae of fetal ethanol exposure are dose-responsive and suggests that there may be a threshold for this effect.

Deductive reasoning and working memory are integral parts of executive functioning and are important skills for blind people in everyday life. Despite the importance of these skills, the influence of visual experience on reasoning and working memory skills, as well as on the relationship between these, is unknown. In this study, fifteen participants with congenital blindness (CB), fifteen with late blindness (LB), fifteen sighted blindfolded controls (SbfC), and fifteen sighted participants performed two tasks of deductive reasoning and two of working memory. We found that while the CB and LB participants did not differ in their deductive reasoning abilities, the CB group performed worse than the sighted controls, and the LB group performed better than the SbfC group. Those with CB outperformed all the other groups in both of the working memory tests. Working memory is associated with deductive reasoning in all three visually impaired groups, but not in the sighted group. These findings suggest that deductive reasoning is not a uniform skill, and that it is associated with visual impairment onset, the level of reasoning difficulty, and the degree of working memory load.

The brain operates through the synaptic interaction of distant neurons within flexible, often heterogeneous, distributed systems. Histological studies have detailed the connections between distant neurons, but their functional characterization deserves further exploration. Studies performed on the corpus callosum in animals and humans are unique in that they capitalize on results obtained from several neuroscience disciplines. Such data inspire a new interpretation of the function of callosal connections and delineate a novel road map, thus paving the way toward a general theory of cortico-cortical connectivity. Here we suggest that callosal axons can drive their post-synaptic targets preferentially when coupled to other inputs endowing the cortical network with a high degree of conditionality. This might depend on several factors, such as their pattern of convergence-divergence, the excitatory and inhibitory operation mode, the range of conduction velocities, the variety of homotopic and heterotopic projections and, finally, the state-dependency of their firing. We propose that, in addition to direct stimulation of post-synaptic targets, callosal axons often play a conditional driving or modulatory role, which depends on task contingencies, as documented by several recent studies., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The endocannabinoid (eCB) system has been found in all visual parts of the central ner-vous system and plays a role in the processing of visual information in many species, including monkeys and humans. Using anatomical methods, cannabinoid receptors are present in the monkey retina, particularly in the vertical glutamatergic pathway, and also in the horizontal GABAergic pathway. Modulating the eCB system regulates normal retinal function as demonstrated by electrophysiological recordings. The characterization of the expression patterns of all types of cannabinoid receptors in the retina is progressing, and further research is needed to elucidate their exact role in processing visual information. Typical cannabinoid receptors include G-protein coupled receptor CB1R and CB2R, and atypical cannabinoid receptors include the G-protein coupled receptor 55 (GPR55) and the ion channel transient receptor potential vanilloid 1 (TRPV1). This review focuses on the expression and localization studies carried out in monkeys, but some data on other animal species and humans will also be reported. Furthermore, the role of the endogenous cannabinoid receptors in retinal function will also be presented using intraocular injections of known modulators (agonists and antagonists) on electroretinographic patterns in monkeys. The effects of the natural bioactive lipid lysophosphatidylglucoside and synthetic FAAH inhibitor URB597 on retinal function, will also be described. Finally, the potential of typical and atypical cannabinoid receptor acti-vity regulation in retinal diseases, such as age-related macular degeneration, diabetic retinopathy, glaucoma, and retinitis pigmentosa will be briefly explored.

Recent studies using full-field electroretinography (ffERG) that triggers a non-specific mass response generated by several retinal sources have attributed an important role for cannabinoid receptors in mediating vision in primates. Specific cone-mediated responses evoked through the photopic flicker ERG appear to be a better way to validate the assumption that endogenous cannabinoids modulate the cone pathway, since FAAH is mainly expressed in the vervet monkey cone photoreceptors. The aim of this study is two-fold: (1) to use the photopic flicker ERG to target the cone pathway specifically, and (2) use URB597 as a selective inhibitor of the endocannabinoid degrading enzyme Fatty Acid Amide Hydrolase (FAAH) to enhance the levels of fatty acid amides, particularly anandamide. We recorded ERGs under four different flicker frequencies (15, 20, 25, and 30 Hz) in light-adapted conditions after intravitreal injections of URB597. Our results show that intravitreal injections of URB597, compared to the vehicle DMSO, increased significantly ffERG amplitudes at 30 Hz, a frequency that solely recruits cone activity. However, at 15 Hz, a frequency that activates both rods and cones, no significant difference was found in the ERG response amplitude. Additionally, we found no differences in implicit times after URB597 injections compared to DMSO vehicle. These results support the role of molecules degraded by FAAH in cone-mediated vision in non-human primates.

The expression of the endocannabinoid (eCB) system, including cannabinoid receptor type 1 (CB1R) and the cannabinoid synthesizing (NAPE-PLD) and degrading (FAAH) enzymes, has been well-characterized in the retina of rodents and monkeys. More recently, the presence of CB1R was localized throughout the dorsal lateral geniculate nucleus of the thalamus of vervet monkeys. Given that the retina projects also to the pulvinar either via a direct projection or via the superior colliculus, it was reasonable to assume that this system would be present therein. The visual pulvinar, namely the inferior pulvinar (PI) region, was delineated with calbindin immunohistochemical staining. Using Western blots and immunofluorescence, we demonstrated that CB1R, NAPE-PLD and FAAH are expressed in the PI of the vervet monkey. Throughout the PI, CB1R was mainly colocalized with VGLUT2-positive axon terminals in the vicinity of calbindin and parvalbumin-positive neurons. NAPE-PLD and FAAH rather colocalized with calbindin over the somatodendritic compartment of PI neurons. Our results suggest that visual information coming from the retina and entering the PI is modulated by the eCB system on its way to the dorsal visual stream. These results provide insights for understanding the role of eCBs in the modulation of visual thalamic inputs and, hence, visual perception.

Neuroimaging with functional MRI (fMRI) identifies activated and deactivated brain regions in task-based paradigms. These patterns of (de)activation are altered in diseases, motivating research to understand their underlying biochemical/biophysical mechanisms. Essentially, it remains unknown how aerobic metabolism of glucose to lactate (aerobic glycolysis) and excitatory-inhibitory balance of glutamatergic and GABAergic neuronal activities vary in these areas. In healthy volunteers, we investigated metabolic distinctions of activating visual cortex (VC, a task-positive area) using a visual task and deactivating posterior cingulate cortex (PCC, a task-negative area) using a cognitive task. We used fMRI-guided J-edited functional MRS (fMRS) to measure lactate, glutamate plus glutamine (Glx) and γ-aminobutyric acid (GABA), as indicators of aerobic glycolysis and excitatory-inhibitory balance, respectively. Both lactate and Glx increased upon activating VC, but did not change upon deactivating PCC. Basal GABA was negatively correlated with BOLD responses in both brain areas, but during functional tasks GABA decreased in VC upon activation and GABA increased in PCC upon deactivation, suggesting BOLD responses in relation to baseline are impacted oppositely by task-induced inhibition. In summary, opposite relations between BOLD response and GABAergic inhibition, and increases in aerobic glycolysis and glutamatergic activity distinguish the BOLD response in (de)activated areas.

Vision loss has dramatic repercussions on the quality of life of affected people, particularly with respect to their orientation and mobility. Many devices are available to help blind people to navigate in their environment. The EyeCane is a recently developed electronic travel aid (ETA) that is inexpensive and easy to use, allowing for the detection of obstacles lying ahead within a 2 m range. The goal of this study was to investigate the potential of the EyeCane as a primary aid for spatial navigation. Three groups of participants were recruited: early blind, late blind, and sighted. They were first trained with the EyeCane and then tested in a life-size obstacle course with four obstacles types: cube, door, post, and step. Subjects were requested to cross the corridor while detecting, identifying, and avoiding the obstacles. Each participant had to perform 12 runs with 12 different obstacles configurations. All participants were able to learn quickly to use the EyeCane and successfully complete all trials. Amongst the various obstacles, the step appeared to prove the hardest to detect and resulted in more collisions. Although the EyeCane was effective for detecting obstacles lying ahead, its downward sensor did not reliably detect those on the ground, rendering downward obstacles more hazardous for navigation.

Blind individuals often report difficulties to navigate and to detect objects placed outside their peri-personal space. Although classical sensory substitution devices could be helpful in this respect, these devices often give a complex signal which requires intensive training to analyze. New devices that provide a less complex output signal are therefore needed. Here, we evaluate a smartphone-based sensory substitution device that offers navigation guidance based on strictly spatial cues in the form of horizontally spatialized sounds. The system uses multiple sensors to either detect obstacles at a distance directly in front of the user or to create a 3D map of the environment (detection and avoidance mode, respectively), and informs the user with auditory feedback. We tested 12 early blind, 11 late blind and 24 blindfolded-sighted participants for their ability to detect obstacles and to navigate in an obstacle course. The three groups did not differ in the number of objects detected and avoided. However, early blind and late blind participants were faster than their sighted counterparts to navigate through the obstacle course. These results are consistent with previous research on sensory substitution showing that vision can be replaced by other senses to improve performance in a wide variety of tasks in blind individuals. This study offers new evidence that sensory substitution devices based on horizontally spatialized sounds can be used as a navigation tool with a minimal amount of training., Competing Interests: The authors have declared that no competing interests exist.

The loss or absence of vision is probably one of the most incapacitating events that can befall a human being. The importance of vision for humans is also reflected in brain anatomy as approximately one third of the human brain is devoted to vision. It is therefore unsurprising that throughout history many attempts have been undertaken to develop devices aiming at substituting for a missing visual capacity. In this review, we present two concepts that have been prevalent over the last two decades. The first concept is sensory substitution, which refers to the use of another sensory modality to perform a task that is normally primarily sub-served by the lost sense. The second concept is cross-modal plasticity, which occurs when loss of input in one sensory modality leads to reorganization in brain representation of other sensory modalities. Both phenomena are training-dependent. We also briefly describe the history of blindness from ancient times to modernity, and then proceed to address the means that have been used to help blind individuals, with an emphasis on modern technologies, invasive (various type of surgical implants) and non-invasive devices. With the advent of brain imaging, it has become possible to peer into the neural substrates of sensory substitution and highlight the magnitude of the plastic processes that lead to a rewired brain. Finally, we will address the important question of the value and practicality of the available technologies and future directions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ptito, Bleau, Djerourou, Paré, Schneider and Chebat.)

Vision loss early in life has dramatic consequences on the organization of the visual system and hence on structural plasticity of its remnant components. Most of the studies on the anatomical changes in the brain following visual deprivation have focused on the re-organization of the visual cortex and its afferent and efferent projections. In this study, we performed a quantitative analysis of the volume and size of the optic chiasm, optic nerve, optic tract and the lateral geniculate nucleus (LGN), the retino recipient thalamic nucleus. Analysis was carried out on structural T1-weighted MRIs from 22 congenitally blind (CB), 14 late blind (LB) and 29 age -and sex-matched sighted control (SC) subjects. We manually segmented the optic nerve, optic chiasm and optic tract, while LGN volumes were extracted using in-house software. We also measured voxel intensity of optic nerve, optic chiasm and optic tract. Mean volumes of the optic nerve, optic tract and optic chiasm were reduced by 50 to 60% in both CB and LB participants. No significant differences were found between the congenitally and late-onset blind participants for any of the measures. Our data further revealed reduced white matter voxel intensities in optic nerve, optic chiasm and optic tract in blind compared to sighted participants, suggesting decreased myelin content in the atrophied white matter. The LGN was reduced by 50% and 44% in CB and LB, respectively. In LB, optic nerve volume correlated negatively with the blindness duration index; no such correlation was found for optic chiasm, optic tract and LGN. The observation that despite the absence of visual input about half of the subcortical retinofugal projections are structurally preserved raises the question of their functional role. One possibility is that the surviving fibers play a role in the maintenance of circadian rhythms in the blind through the intrinsically photosensitive melanopsin-containing retinal ganglion cells., (Copyright © 2021. Published by Elsevier Inc.)

Axonal conduction velocity, which ensures efficient function of the brain network, is related to axon diameter. Noninvasive, in vivo axon diameter estimates can be made with diffusion magnetic resonance imaging, but the technique requires three-dimensional (3D) validation. Here, high-resolution, 3D synchrotron X-ray nano-holotomography images of white matter samples from the corpus callosum of a monkey brain reveal that blood vessels, cells, and vacuoles affect axonal diameter and trajectory. Within single axons, we find that the variation in diameter and conduction velocity correlates with the mean diameter, contesting the value of precise diameter determination in larger axons. These complex 3D axon morphologies drive previously reported 2D trends in axon diameter and g -ratio. Furthermore, we find that these morphologies bias the estimates of axon diameter with diffusion magnetic resonance imaging and, ultimately, impact the investigation and formulation of the axon structure-function relationship., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

In congenital blindness (CB), tactile, and auditory information can be reinterpreted by the brain to compensate for visual information through mechanisms of brain plasticity triggered by training. Visual deprivation does not cause a cognitive spatial deficit since blind people are able to acquire spatial knowledge about the environment. However, this spatial competence takes longer to achieve but is eventually reached through training-induced plasticity. Congenitally blind individuals can further improve their spatial skills with the extensive use of sensory substitution devices (SSDs), either visual-to-tactile or visual-to-auditory. Using a combination of functional and anatomical neuroimaging techniques, our recent work has demonstrated the impact of spatial training with both visual to tactile and visual to auditory SSDs on brain plasticity, cortical processing, and the achievement of certain forms of spatial competence. The comparison of performances between CB and sighted people using several different sensory substitution devices in perceptual and sensory-motor tasks uncovered the striking ability of the brain to rewire itself during perceptual learning and to interpret novel sensory information even during adulthood. We discuss here the implications of these findings for helping blind people in navigation tasks and to increase their accessibility to both real and virtual environments., (Copyright © 2020 Chebat, Schneider and Ptito.)

The ubiquitous distribution of the classic endocannabinoid system (cannabinoid receptors CB1 and CB2) has been demonstrated within the monkey nervous system, including the retina. Transient receptor potential vanilloid type 1 (TRPV1) is a cannabinoid-like non-selective cation channel receptor that is present in the retina and binds to endovannilloids and endocannabinoids, like anandamide, 2-arachidonoylglycerol and N-arachidonoyl dopamine. Retinal expression patterns of TRPV1 are available for rodents and data in higher mammals like humans and monkeys are scarce. We therefore thoroughly examined the expression and localization of TRPV1 in the retina, at various eccentricities, of the vervet (Chlorocebus sabeus) monkey, using Western blots and immunohistochemistry. Our results demonstrate that TRPV1 is found mainly in the outer and inner plexiform layers, and in the retinal ganglion cell (RGC) layer with a higher density in the periphery. Co-immunolabeling of TRPV1 with parvalbumin, a primate horizontal cell marker, revealed a clear overlap of expression throughout the entire cell structure with most prominent staining in the cell body membrane and synaptic terminals. Furthermore, double labeling of TRPV1 and syntaxin was found throughout amacrine cells in the inner plexiform layer. Finally, double staining of TRPV1 and Brn3a allowed us to confirm its previously reported expression in the cell bodies and dendrites of RGCs. The presence of TRPV1 in the horizontal pathway suggests a function of this receptor in lateral inhibition between photoreceptors through the horizontal cells, and between bipolar cells through amacrine cells.

The frontal lobe is central to distinctive aspects of human cognition and behavior. Some comparative studies link this to a larger frontal cortex and even larger frontal white matter in humans compared with other primates, yet others dispute these findings. The discrepancies between studies could be explained by limitations of the methods used to quantify volume differences across species, especially when applied to white matter connections. In this study, we used a novel tractography approach to demonstrate that frontal lobe networks, extending within and beyond the frontal lobes, occupy 66% of total brain white matter in humans and 48% in three monkey species: vervets (Chlorocebus aethiops), rhesus macaque (Macaca mulatta) and cynomolgus macaque (Macaca fascicularis), all male. The simian-human differences in proportional frontal tract volume were significant for projection, commissural, and both intralobar and interlobar association tracts. Among the long association tracts, the greatest difference was found for tracts involved in motor planning, auditory memory, top-down control of sensory information, and visuospatial attention, with no significant differences in frontal limbic tracts important for emotional processing and social behaviour. In addition, we found that a nonfrontal tract, the anterior commissure, had a smaller volume fraction in humans, suggesting that the disproportionally large volume of human frontal lobe connections is accompanied by a reduction in the proportion of some nonfrontal connections. These findings support a hypothesis of an overall rearrangement of brain connections during human evolution. SIGNIFICANCE STATEMENT Tractography is a unique tool to map white matter connections in the brains of different species, including humans. This study shows that humans have a greater proportion of frontal lobe connections compared with monkeys, when normalized by total brain white matter volume. In particular, tracts associated with language and higher cognitive functions are disproportionally larger in humans compared with monkeys, whereas other tracts associated with emotional processing are either the same or disproportionally smaller. This supports the hypothesis that the emergence of higher cognitive functions in humans is associated with increased extended frontal connectivity, allowing human brains more efficient cross talk between frontal and other high-order associative areas of the temporal, parietal, and occipital lobes., (Copyright © 2020 Barrett et al.)

Despite the fact that complete visual deprivation leads to volumetric reductions in brain structures associated with spatial learning, blind individuals are still able to navigate. The neural structures involved in this function are not fully understood. Our study aims to correlate the performance of congenitally blind individuals (CB) and blindfolded sighted controls (SC) in a life-size obstacle-course using a visual-to-tactile sensory substitution device, with the size of brain structures (voxel based morphometry-VBM-) measured through structural magnetic resonance Imaging (MRI). VBM was used to extract grey matter volumes within several a-priori defined brain regions in all participants. Principal component analysis was utilized to group brain regions in factors and orthogonalize brain volumes. Regression analyses were then performed to link learning abilities to these factors. We found that (1) both CB and SC were able to learn to detect and avoid obstacles; (2) their learning rates for obstacle detection and avoidance correlated significantly with the volume of brain structures known to be involved in spatial skills. There is a similar relation between regions of the dorsal stream network and avoidance for both SC and CB whereas for detection, SC rely more on medial temporal lobe structures and CB on sensorimotor areas.

We investigated the effects of blindness on the structural and functional integrity of the corpus callosum and the anterior commissure (AC), which together form the two major components of the commissural pathways. Twelve congenitally blind (CB), 15 late blind (LB; mean onset of blindness of 16.6 ± 8.9 years), and 15 matched normally sighted controls (SC) participated in a multimodal brain imaging study. Magnetic resonance imaging(MRI) data were acquired using a 3T scanner, and included a structural brain scan, resting state functional MRI, and diffusion-weighted imaging. We used tractography to divide the AC into its anterior (aAC) and posterior (pAC) branch. Virtual tract dissection was performed using a deterministic spherical deconvolution tractography algorithm. The corpus callosum was subdivided into five subregions based on the criteria described by Witelson and modified by Bermudez and Zatorre. Our data revealed decreased fractional anisotropy of the pAC in CB and LB compared to SC, together with an increase in the number of streamlines in CB only. In addition, the AC surface area was significantly larger in CB compared to SC and LB, and correlated with the number of streamlines in pAC (rho = 0.55) and tract volume (rho = 0.46). As for the corpus callosum, the splenial part was significantly smaller in CB and LB, and fewer streamlines passed through it. We did not find group differences in functional connectivity of cortical areas connected by fibers crossing any of the five callosal subregions. The present data suggest that the two main components of the commissural system undergo neuroplastic changes, irrespective of the age of onset of blindness, although the alterations observed in the AC are more important in congenital than late-onset blindness., Competing Interests: Declaration of Competing interest None., (Copyright © 2019. Published by Elsevier Inc.)

There is ongoing controversy regarding the role of rapid eye movements (EMs) during rapid eye movement (REM) sleep. One prevailing hypothesis is that EMs during REM sleep are indicative of the presence of visual imagery in dreams. We tested the validity of this hypothesis by measuring EMs in blind subjects and correlating these with visual dream content. Eleven blind subjects, of whom five were congenitally blind (CB) and six late blind (LB), and 11 matched sighted control (SC) subjects participated in this study. All participants underwent full-night polysomnography (PSG) recordings that were staged manually following American Academy of Sleep Medicine (AASM) criteria. Nocturnal EMs were detected automatically using a validated EM detector, and EM activity was represented as "EM coverage" computed as percentage of time with EM in each sleep stage. Frequency of sensory dream elements was measured in dream recall questionnaires over a 30-day period. Both blind groups showed less EM coverage during wakefulness, N1, N2 and REM sleep than did controls. CB and LB subjects did not differ in EM activity. Validation of the detector applied to blind subjects revealed an overall accuracy of 95.6 ± 3.6%. Analysis of dream reports revealed that LB subjects reported significantly more visual dream elements than did CB. Although no specific mechanisms can be revealed in the current study, the quasi absence of nocturnal EMs in LB subjects despite preserved visual dream content does not support the visual scanning of dreams hypothesis. Specifically, results suggest a dissociation between EMs and visual dream content in blind individuals., (© 2019 European Sleep Research Society.)