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There is ample evidence that the occipital cortex of congenitally blind individuals processes nonvisual information. It remains a debate whether the cross-modal activation of the occipital cortex is mediated through the modulation of preexisting corticocortical projections or the reorganisation of thalamocortical connectivity. Current knowledge on this topic largely stems from anatomical studies in animal models. The aim of this study was to test whether purported changes in thalamocortical connectivity in blindness can be revealed by tractography based on diffusion-weighted magnetic resonance imaging. To assess the thalamocortical network, we used a clustering method based on the thalamic white matter projections towards predefined cortical regions. Five thalamic clusters were obtained in each group representing their cortical projections. Although we did not find differences in the thalamocortical network between congenitally blind individuals, late blind individuals, and normal sighted controls, diffusion tensor imaging (DTI) indices revealed significant microstructural changes within thalamic clusters of both blind groups. Furthermore, we find a significant decrease in fractional anisotropy (FA) in occipital and temporal thalamocortical projections in both blind groups that were not captured at the network level. This suggests that plastic microstructural changes have taken place, but not in a degree to be reflected in the tractography-based thalamocortical network. [ABSTRACT FROM AUTHOR]

Background: We have recently shown that visual deprivation from birth exacerbates responses to painful thermal stimuli. However, the mechanisms underlying pain hypersensitivity in congenital blindness are unclear.Methods: To study the contribution of Aδ- and C-fibres in pain perception, we measured thresholds and response times to selective C- and Aδ-fibre activation in congenitally blind, late blind and normally sighted participants. Ultrafast constant-temperature heat pulses were delivered to the hand with a CO2 laser using an interleaved adaptive double staircase procedure. Participants were instructed to respond as quickly as possible when detecting a laser-induced sensation. We used a 650 ms cut-off criterion to distinguish fast Aδ- from slow C-fibre-mediated sensations.Results: Congenitally blind participants showed significantly faster reaction times to C- but not to Aδ-fibre-mediated sensations. In contrast, thresholds for Aδ- and C-fibre stimulation did not differ between groups. Late blind individuals did not differ from sighted controls in any aspect. A follow-up experiment using only suprathreshold stimuli for Aδ- and C-fibre activation confirmed these findings and further showed that congenitally blind individuals detected significantly more C-fibre-mediated stimuli than sighted controls. A decomposition analysis of the reaction times indicated that the faster response times in the congenitally blind are due to more efficient central processing of C-fibre-mediated sensations.Conclusion: The increased sensitivity to painful thermal stimulation in congenital blindness may be due to more efficient central processing of C-fibre-mediated input, which may help to avoid impending dangerous encounters with stimuli that threaten the bodily integrity. WHAT DOES THIS STUDY ADD?: Hypersensitivity to heat pain in congenital blindness is associated with faster responses to C-fibre activation, likely caused by more efficient central processing of C-fibre-mediated input. [ABSTRACT FROM AUTHOR]

Abstract: The endocannabinoid (eCB) system is thought to participate in developmental processes in the CNS. The rodent retina represents a valuable model to study CNS development because it contains well-identified cell types with established developmental timelines. The distribution of cannabinoid receptor type 1 (CB1R) was recently revealed in the developing retina; however, the expression patterns of other elements of this system remain unknown. In this study, we investigated the expression pattern of the degradative enzyme fatty acid amide hydrolase (FAAH), a key regulator of the eCB system, in the rat retina during postnatal development. To identify the cells expressing the enzyme, co-stainings were carried out for FAAH and retinal cell type markers. FAAH was expressed at postnatal day (P) 1 in ganglion and cholinergic amacrine cells. In the course of development, it appeared in cones, horizontal, and bipolar cells. For most cell types (horizontal, cholinergic amacrine cells, and cone bipolar cells), FAAH was transiently expressed, suggesting an important redistribution of the enzyme during postnatal development and thus a potential role of the eCB system in developmental processes. Our results also indicated that, in the adult retina, FAAH is expressed in cones, rod bipolar cells, and some retinal ganglion cells. The presence of FAAH in adult animals supports the hypothesis that the eCB system is involved in retinal functions. Overall these results indicate that, as shown in other structures of the brain, the eCB system could play an instrumental role in the development and function of the retina. [Copyright &y& Elsevier]

Abstract: In cats, it is generally believed that the visual part of the anterior ectosylvian cortex (AEV) is involved in motion integration. It receives a substantial proportion of its afferents from cortical (e.g. lateral suprasylvian cortex) and sub-cortical (e.g. lateral posterior–pulvinar complex) areas known to participate in complex motion analysis. It has been established that a subset of AEV neurons can code the veridical motion of a moving plaid pattern (pattern-motion selectivity). In our study, we have further investigated the possibility that AEV neurons may play a role in higher-order motion processing by studying their responses to complex stimuli which necessitate higher order spatial and temporal integration. Experiments were performed in anesthetized adult cats. Classical receptive fields were stimulated with (1) complex random-dot kinematograms (RDKs), where the individual elements of the pattern do not provide coherent motion cues; (2) optic flow fields which require global spatial integration. We report that a large proportion of AEV neurons were selective to the direction and speed of RDKs. Close to two-thirds of the cells were selective to the direction of optic flow fields with about equal proportions being selective to contraction and expansion. The complex RDK and optic flow responsive units could not be systematically characterized based on their responses to plaid patterns; they were either pattern- or component-motion selective. These findings support the proposal that AEV is involved in higher-order motion processing. Our data suggest that the AEV may be more involved in the analysis of motion of visual patterns in relation to the animal’s behavior rather than the analysis of the constituents of the patterns. [Copyright &y& Elsevier]

AbstractNumerous functional and hodological studies of the anterior ectosylvian visual area (AEV) of the cerebral cortex of the cat suggest that this area plays an important role in processing information about visual motion. In the present study, in cats with selective conduction block of Y fibres in one optic nerve, we have examined the extent of the excitatory convergence of Y (presumed ‘motion channel') and non‐Y information channels on single neurons in AEV, as well as the contribution of the Y channel to the receptive field properties of AEV neurons. While in normal cats all neurons recorded from AEV were binocular, i.e. could be photically activated via either eye, in cats with selective conduction block of Y fibres in one optic nerve, a significant proportion (about 15%) of AEV cells could be photically activated only via the normal eye. In comparison to those in normal cats, the peak discharge rates of AEV neurons in the Y‐blocked cats were drastically reduced not only when photic stimuli were presented via the Y‐blocked eye, but also when they were presented via the normal eye. Selective block of Y input also resulted in a significant shift in velocity preferences towards the lower velocities. However, the direction selectivity indices of AEV neurons were not affected by selective Y block. Thus: (i) the responses of AEV neurons to a high velocity of motion are dependent on the integrity of the Y input; (ii) the ‘spontaneous' (i.e. not photically evoked) discharges of Y retinal ganglion cells exert a facilitatory influence on the responses of AEV cells to photic stimuli; (iii) although the responses of AEV neurons are dominated by the Y inputs, AEV neurons also receive significant non‐Y excitatory inputs; and (iv) the strong direction selectivity revealed in most AEV neurons does not dependent on the integrity of Y input. [ABSTRACT FROM AUTHOR]

We have shown that congenitally blind individuals are more sensitive to painful heat compared to their sighted counterparts. This hypersensitivity might be at least partly mediated by psychological and cognitive factors, such as pain expectation and anxiety. Here we investigate whether uncertainty about the intensity of a pending painful stimulus affects pain differently in congenitally blind and sighted control subjects. We measured pain and anxiety in a group of 11 congenitally blind and 11 age- and sex-matched normal sighted control participants. Painful stimuli were delivered under two psychological conditions, whereby participants were either certain or uncertain about the intensity of a pending noxious stimuli. Although both blind and sighted participants had increased anxiety ratings in the uncertain condition, pain ratings increased only in the congenitally blind participants. Our data therefore indicate that increased anxiety levels have a stronger influence on the perceived pain intensity in blind individuals, possibly because they allocate greater attention to signals of external threat. [ABSTRACT FROM AUTHOR]

Abstract: In the present study, we tested the hypothesis that the expression of calcium binding proteins (CaBPs), parvalbumin (PV), calretinin (CR) and calbindin (CB), is dependent upon sensory experience as emphasized in visual deprivation and deafferentation studies. The expression of CaBPs was studied in interneurons within the primary and extrastriate visual cortices (V1, V2M, V2L) and auditory cortex (AC) of adult hamsters enucleated at birth. The effects of enucleation were mainly confined to area V1 where there was a significant volume reduction (26%) and changes in the laminar distribution of PV and CB immunoreactive (IR) cells. The density of PV–IR cell bodies was significantly increased in layer IV and reduced in layer V. Moreover, the density of CB–IR neurons was inferior in layer V of V1 in enucleated hamsters (EH) compared to controls. These results suggest that some features of the laminar distribution of specific CaBPs, in primary sensory cortices, are dependent upon or modulated by sensory input. [ABSTRACT FROM AUTHOR]

The endocannabinoid system mainly consists of cannabinoid receptors type 1 (CB1R) and type 2 (CB2R), their endogenous ligands termed endocannabinoids (eCBs), and the enzymes responsible for the synthesis and degradation of eCBs. These cannabinoid receptors have been well characterized in rodent and monkey retinae. Here, we investigated the expression and localization of the eCB system beyond the retina, namely the first thalamic relay, the dorsal lateral geniculate nucleus (dLGN), of vervet monkeys using immunohistochemistry methods. Our results show that CB1R is expressed throughout the dLGN with more prominent labeling in the magnocellular layers. The same pattern is observed for the degradation enzyme, fatty acid amide hydrolase (FAAH). However, the synthesizing enzyme N-acyl-phosphatidylethanolamine phospholipase D (NAPE-PLD) is expressed homogenously throughout the dLGN with no preference for any of the layers. These proteins are weakly expressed in the koniocellular layers. These results suggest that the presence of the eCB system throughout the layers of the dLGN may represent a novel site of neuromodulatory action in normal vision. The larger amount of CB1R in the dLGN magnocellular layers may explain some of the behavioral effects of cannabinoids associated with the integrity of the dorsal visual pathway that plays a role in visual-spatial localization and motion perception. [ABSTRACT FROM AUTHOR]

Abstract: The presence of a widespread endocannabinoid (eCB) system within the nervous system, including the retina, has been demonstrated in recent years. Expression patterns of the cannabinoid receptor type 1 (CB1R) and enzyme fatty acid amide hydrolase (FAAH) are available for rodents, but data for humans and monkeys are scarce. We, therefore, thoroughly examined the distribution pattern of CB1R and FAAH throughout the retina of the vervet monkey (Chlorocebus sabeus) using confocal microscopy. Our results demonstrate that CB1R and FAAH are expressed throughout the retina, from the foveal pit to the far periphery. CB1R and FAAH are present in the photoreceptor, outer plexiform, inner nuclear, inner plexiform, and retinal ganglion cell layers (PRL, OPL, INL, IPL, and RGCL, respectively). More specifically, in PRL, CB1R and FAAH are preferentially expressed in cones of the central retina. In OPL, these two components of the eCB system are concentrated not only in the cone pedicles but also in rod spherules with, however, a less intense staining pattern. Triple-labeling immunofluorescence revealed that both cone and rod bipolar cells express CB1R and FAAH. Heavy staining is detected in RGC somas and axons. Neither CB1R nor FAAH are found in the retinal glia, the Müller cells. These data indicate that the eCB system is present throughout the primate retina and is ideally positioned to modulate central and peripheral retinal functions. [Copyright &y& Elsevier]

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).)