Simple visual stimuli are sufficient to drive responses in action observation and execution neurons in macaque ventral premotor cortex.

Neurons responding during action execution and action observation were discovered in the ventral premotor cortex 3 decades ago. However, the visual features that drive the responses of action observation/execution neurons (AOENs) have not been revealed at present. We investigated the neural responses of AOENs in ventral premotor area F5c of 4 macaques during the observation of action videos and crucial control stimuli. The large majority of AOENs showed highly phasic responses during the action videos, with a preference for the moment that the hand made contact with the object. They also responded to an abstract shape moving towards but not interacting with an object, even when the shape moved on a scrambled background, implying that most AOENs in F5c do not require the perception of causality or a meaningful action. Additionally, the majority of AOENs responded to static frames of the videos. Our findings show that very elementary stimuli, even without a grasping context, are sufficient to drive responses in F5c AOENs.

Diversity and community structure of anaerobic gut fungi in the rumen of wild and domesticated herbivores.

The rumen houses a diverse community that plays a major role in the digestion process in ruminants. Anaerobic gut fungi (AGF) are key contributors to plant digestion in the rumen. Here, we present a global amplicon-based survey of the rumen AGF mycobiome by examining 206 samples from 15 animal species, 15 countries, and 6 continents. The rumen AGF mycobiome was highly diverse, with 81 out of 88 currently recognized AGF genera or candidate genera identified. However, only six genera (Neocallimastix, Orpinomyces, Caecomyces, Cyllamyces, NY9, and Piromyces) were present at >4% relative abundance. AGF diversity was higher in members of the families Antilocapridae and Cervidae compared to Bovidae. Community structure analysis identified a pattern of phylosymbiosis, where host family (10% of total variance) and species (13.5%) partially explained the rumen mycobiome composition. As well, diet composition (9%-19%), domestication (11.14%), and biogeography (14.1%) also partially explained AGF community structure; although sampling limitation, geographic range restrictions, and direct association between different factors hindered accurate elucidation of the relative contribution of each factor. Pairwise comparison of rumen and fecal samples obtained from the same subject (n = 13) demonstrated greater diversity and inter-sample variability in rumen versus fecal samples. The genera Neocallimastix and Orpinomyces were present in higher abundance in rumen samples, while Cyllamyces and Caecomyces were enriched in fecal samples. Comparative analysis of global rumen and feces data sets revealed a similar pattern. Our results provide a global view of AGF community in the rumen and identify patterns of AGF variability between rumen and feces in herbivores Gastrointestinal (GI) tract.IMPORTANCERuminants are highly successful and economically important mammalian suborder. Ruminants are herbivores that digest plant material with the aid of microorganisms residing in their GI tract. In ruminants, the rumen compartment represents the most important location where microbially mediated plant digestion occurs, and is known to house a bewildering array of microbial diversity. An important component of the rumen microbiome is the anaerobic gut fungi (AGF), members of the phylum Neocallimastigomycota. So far, studies examining AGF diversity have mostly employed fecal samples, and little is currently known regarding the identity of AGF residing in the rumen compartment, factors that impact the observed patterns of diversity and community structure of AGF in the rumen, and how AGF communities in the rumen compare to AGF communities in feces. Here, we examined the rumen AGF diversity using an amplicon-based survey targeting a wide range of wild and domesticated ruminants (n = 206, 15 different animal species) obtained from 15 different countries. Our results demonstrate that while highly diverse, no new AGF genera were identified in the rumen mycobiome samples examined. Our analysis also indicate that animal host phylogeny, diet, biogeography, and domestication status could play a role in shaping AGF community structure. Finally, we demonstrate that a greater level of diversity and higher inter-sample variability was observed in rumen compared to fecal samples, with two genera (Neocallimastix and Orpinomyces) present in higher abundance in rumen samples, and two others (Cyllamyces and Caecomyces) enriched in fecal samples. Our results provide a global view of the identity, diversity, and community structure of AGF in ruminants, elucidate factors impacting diversity and community structure of the rumen mycobiome, and identify patterns of AGF community variability between the rumen and feces in the herbivorous GI tract.

Active and Passive Cycling Decrease Subthalamic ß Oscillations in Parkinson's Disease.

BACKGROUND: Preserved cycling capabilities in patients with Parkinson's disease, especially in those with freezing of gait are still poorly understood. Previous research with invasive local field potential recordings in the subthalamic nucleus has shown that cycling causes a stronger suppression of ß oscillations compared to walking, which facilitates motor continuation. METHODS: We recorded local field potentials from 12 patients with Parkinson's disease (six without freezing of gait, six with freezing of gait) who were bilaterally implanted with deep brain stimulation electrodes in the subthalamic nucleus. We investigated ß (13-30 Hz) and high γ (60-100 Hz) power during both active and passive cycling with different cadences and compared patients with and without freezing of gait. The passive cycling experiment, where a motor provided a fixed cadence, allowed us to study the effect of isolated sensory inputs without physical exercise. RESULTS: We found similarly strong suppression of pathological ß activity for both active and passive cycling. In contrast, there was stronger high γ band activity for active cycling. Notably, the effects of active and passive cycling were all independent of cadence. Finally, ß suppression was stronger for patients with freezing of gait, especially during passive cycling. CONCLUSIONS: Our results provide evidence for a link between proprioceptive input during cycling and ß suppression. These findings support the role of continuous external sensory input and proprioceptive feedback during rhythmic passive cycling movements and suggest that systematic passive mobilization might hold therapeutic potential. © 2023 International Parkinson and Movement Disorder Society.

Effect of buffer pH on methane production and fermentation characteristics of three forages tested in vitro.

BACKGROUND: Low rumen pH is proposed to be a major mechanism for low methane (CH4) emissions from sheep fed forage rape. However, it is difficult to separate this from other in vivo factors, such as rumen passage rate. The objective of this study was to determine the effect of pH alone on CH4 production in vitro using different pH buffers. Ryegrass, white clover and forage rape were incubated in vitro using three different incubation buffers with starting pH values of 5.5, 6.2 and 6.8. RESULTS: Decreasing pH reduced overall in vitro CH4 emission relative to fermented hexoses (CH4/FHex) by up to 54% and overall fermentation by 40%. pH also changed fermentation profiles where the acetate + butyrate to propionate + valerate ratio decreased when pH decreased. Within the three forages, forage rape led to the lowest CH4/FHex, but only in pH 5.5 and 6.2 buffer, and this was enhanced when the pH fell below 6. CONCLUSION: Reducing pH in vitro decreased CH4 production and overall fermentation across all forages. The lower pH reached by forage rape compared to ryegrass and white clover appears to drive the lower CH4 production relative to the extent of fermentation from forage rape compared to the other forages. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Large-scale analysis of sheep rumen metagenome profiles captured by reduced representation sequencing reveals individual profiles are influenced by the environment and genetics of the host.

BACKGROUND: Producing animal protein while reducing the animal's impact on the environment, e.g., through improved feed efficiency and lowered methane emissions, has gained interest in recent years. Genetic selection is one possible path to reduce the environmental impact of livestock production, but these traits are difficult and expensive to measure on many animals. The rumen microbiome may serve as a proxy for these traits due to its role in feed digestion. Restriction enzyme-reduced representation sequencing (RE-RRS) is a high-throughput and cost-effective approach to rumen metagenome profiling, but the systematic (e.g., sequencing) and biological factors influencing the resulting reference based (RB) and reference free (RF) profiles need to be explored before widespread industry adoption is possible. RESULTS: Metagenome profiles were generated by RE-RRS of 4,479 rumen samples collected from 1,708 sheep, and assigned to eight groups based on diet, age, time off feed, and country (New Zealand or Australia) at the time of sample collection. Systematic effects were found to have minimal influence on metagenome profiles. Diet was a major driver of differences between samples, followed by time off feed, then age of the sheep. The RF approach resulted in more reads being assigned per sample and afforded greater resolution when distinguishing between groups than the RB approach. Normalizing relative abundances within the sampling Cohort abolished structures related to age, diet, and time off feed, allowing a clear signal based on methane emissions to be elucidated. Genus-level abundances of rumen microbes showed low-to-moderate heritability and repeatability and were consistent between diets. CONCLUSIONS: Variation in rumen metagenomic profiles was influenced by diet, age, time off feed and genetics. Not accounting for environmental factors may limit the ability to associate the profile with traits of interest. However, these differences can be accounted for by adjusting for Cohort effects, revealing robust biological signals. The abundances of some genera were consistently heritable and repeatable across different environments, suggesting that metagenomic profiles could be used to predict an individual's future performance, or performance of its offspring, in a range of environments. These results highlight the potential of using rumen metagenomic profiles for selection purposes in a practical, agricultural setting.

Visual guidance in control of grasping.

Humans and other primates possess a unique capacity to grasp and manipulate objects skillfully, a facility pervasive in everyday life that has undoubtedly contributed to the success of our species. When we reach and grasp an object, various cortical areas in the parietal and frontal lobes work together effortlessly to analyze object shape and position, transform this visual information into useful motor commands, and implement these motor representations to preshape the hand before contact with the object is made. In recent years, a growing number of studies have investigated the neural circuits underlying object grasping in both the visual and motor systems of the macaque monkey. The accumulated knowledge not only helps researchers understand how object grasping is implemented in the primate brain but may also contribute to the development of novel neural interfaces and neuroprosthetics.

Rumen Lachnospiraceae isolate NK3A20 exhibits metabolic flexibility in response to substrate and coculture with a methanogen.

Hydrogen (H2) is the primary electron donor for methane formation in ruminants, but the H2-producing organisms involved are largely uncharacterized. This work integrated studies of microbial physiology and genomics to characterize rumen bacterial isolate NK3A20 of the family Lachnospiraceae. Isolate NK3A20 was the first recognized isolate of the NK3A20 group, which is among the ten most abundant bacterial genera in 16S rRNA gene surveys of rumen microbiota. NK3A20 produced acetate, butyrate, H2, and formate from glucose. The end product ratios varied when grown with different substrates and at different H2 partial pressures. NK3A20 produced butyrate as a major product using glucose or under high H2 partial pressures and switched to mainly acetate in the presence of galacturonic acid (an oxidized sugar) or in coculture with a methanogen. Growth with galacturonic acid was faster at elevated H2 concentrations, while elevated H2 slowed growth with glucose. Genome analyses revealed the presence of multiple hydrogenases including a membrane-bound Ech hydrogenase, an electron bifurcating butyryl-CoA dehydrogenase (Bcd-Etf), and an Rnf complex that may be involved in modulating the observed metabolic pathway changes, providing insight into H2 formation in the rumen. IMPORTANCE The genus-level NK3A20 group is one of the ten most abundant genera of rumen bacteria. Like most of the rumen bacteria that produce the hydrogen that is converted to methane in the rumen, it is understudied, without any previously characterized isolates. We investigated isolate NK3A20, a cultured member of this genus, and showed that it modulates hydrogen production in response to its growth substrates and the hydrogen concentration in its environment. Low-hydrogen concentrations stimulated hydrogen formation, while high concentrations inhibited its formation and shifted the fermentation to more reduced organic acid products. We found that growth on uronic acids, components of certain plant polymers, resulted in low hydrogen yields compared to glucose, which could aid in the selection of low-methane feeds. A better understanding of the major genera that produce hydrogen in the rumen is part of developing strategies to mitigate biogenic methane emitted by livestock agriculture.

Aristaeella hokkaidonensis gen. nov. sp. nov. and Aristaeella lactis sp. nov., two rumen bacterial species of a novel proposed family, Aristaeellaceae fam. nov.

Two strains of Gram-negative, anaerobic, rod-shaped bacteria, from an abundant but uncharacterized rumen bacterial group of the order 'Christensenellales', were phylogenetically and phenotypically characterized. These strains, designated R-7T and WTE2008T, shared 98.6-99.0 % sequence identity between their 16S rRNA gene sequences. R-7T and WTE2008T clustered together on a distinct branch from other Christensenellaceae strains and had <88.1 % sequence identity to the closest type-strain sequence from Luoshenia tenuis NSJ-44T. The genome sequences of R-7T and WTE2008T had 83.6 % average nucleotide identity to each other, and taxonomic assignment using the Genome Taxonomy Database indicates these are separate species within a novel family of the order 'Christensenellales'. Cells of R-7T and WTE2008T lacked any obvious appendages and their cell wall ultra-structures were characteristic of Gram-negative bacteria. The five most abundant cellular fatty acids of both strains were C16 : 0, C16 : 0 iso, C17 : 0 anteiso, C18 : 0 and C15 : 0 anteiso. The strains used a wide range of the 23 soluble carbon sources tested, and grew best on cellobiose, but not on sugar-alcohols. Xylan and pectin were fermented by both strains, but not cellulose. Acetate, hydrogen, ethanol and lactate were the major fermentation end products. R-7T produced considerably more hydrogen than WTE2008T, which produced more lactate. Based on these analyses, Aristaeellaceae fam. nov. and Aristaeella gen. nov., with type species Aristaeella hokkaidonensis sp. nov., are proposed. Strains R-7T (=DSM 112795T=JCM 34733T) and WTE2008T (=DSM 112788T=JCM 34734T) are the proposed type strains for Aristaeella hokkaidonensis sp. nov. and Aristaeella lactis sp. nov., respectively.

Combining host and rumen metagenome profiling for selection in sheep: prediction of methane, feed efficiency, production, and health traits.

BACKGROUND: Rumen microbes break down complex dietary carbohydrates into energy sources for the host and are increasingly shown to be a key aspect of animal performance. Host genotypes can be combined with microbial DNA sequencing to predict performance traits or traits related to environmental impact, such as enteric methane emissions. Metagenome profiles were generated from 3139 rumen samples, collected from 1200 dual purpose ewes, using restriction enzyme-reduced representation sequencing (RE-RRS). Phenotypes were available for methane (CH4) and carbon dioxide (CO2) emissions, the ratio of CH4 to CH4 plus CO2 (CH4Ratio), feed efficiency (residual feed intake: RFI), liveweight at the time of methane collection (LW), liveweight at 8 months (LW8), fleece weight at 12 months (FW12) and parasite resistance measured by faecal egg count (FEC1). We estimated the proportion of phenotypic variance explained by host genetics and the rumen microbiome, as well as prediction accuracies for each of these traits. RESULTS: Incorporating metagenome profiles increased the variance explained and prediction accuracy compared to fitting only genomics for all traits except for CO2 emissions when animals were on a grass diet. Combining the metagenome profile with host genotype from lambs explained more than 70% of the variation in methane emissions and residual feed intake. Predictions were generally more accurate when incorporating metagenome profiles compared to genetics alone, even when considering profiles collected at different ages (lamb vs adult), or on different feeds (grass vs lucerne pellet). A reference-free approach to metagenome profiling performed better than metagenome profiles that were restricted to capturing genera from a reference database. We hypothesise that our reference-free approach is likely to outperform other reference-based approaches such as 16S rRNA gene sequencing for use in prediction of individual animal performance. CONCLUSIONS: This paper shows the potential of using RE-RRS as a low-cost, high-throughput approach for generating metagenome profiles on thousands of animals for improved prediction of economically and environmentally important traits. A reference-free approach using a microbial relationship matrix from log10 proportions of each tag normalized within cohort (i.e., the group of animals sampled at the same time) is recommended for future predictions using RE-RRS metagenome profiles.

Single-Unit Recordings Reveal the Selectivity of a Human Face Area.

The exquisite capacity of primates to detect and recognize faces is crucial for social interactions. Although disentangling the neural basis of human face recognition remains a key goal in neuroscience, direct evidence at the single-neuron level is limited. We recorded from face-selective neurons in human visual cortex in a region characterized by functional magnetic resonance imaging (fMRI) activations for faces compared with objects. The majority of visually responsive neurons in this fMRI activation showed strong selectivity at short latencies for faces compared with objects. Feature-scrambled faces and face-like objects could also drive these neurons, suggesting that this region is not tightly tuned to the visual attributes that typically define whole human faces. These single-cell recordings within the human face processing system provide vital experimental evidence linking previous imaging studies in humans and invasive studies in animal models.SIGNIFICANCE STATEMENT We present the first recordings of face-selective neurons in or near an fMRI-defined patch in human visual cortex. Our unbiased multielectrode array recordings (i.e., no selection of neurons based on a search strategy) confirmed the validity of the BOLD contrast (faces-objects) in humans, a finding with implications for all human imaging studies. By presenting faces, feature-scrambled faces, and face-pareidolia (perceiving faces in inanimate objects) stimuli, we demonstrate that neurons at this level of the visual hierarchy are broadly tuned to the features of a face, independent of spatial configuration and low-level visual attributes.

Correction: Single-cell selectivity and functional architecture of human lateral occipital complex.

[This corrects the article DOI: 10.1371/journal.pbio.3000280.].

Single-cell selectivity and functional architecture of human lateral occipital complex.

The human lateral occipital complex (LOC) is more strongly activated by images of objects compared to scrambled controls, but detailed information at the neuronal level is currently lacking. We recorded with microelectrode arrays in the LOC of 2 patients and obtained highly selective single-unit, multi-unit, and high-gamma responses to images of objects. Contrary to predictions derived from functional imaging studies, all neuronal properties indicated that the posterior subsector of LOC we recorded from occupies an unexpectedly high position in the hierarchy of visual areas. Notably, the response latencies of LOC neurons were long, the shape selectivity was spatially clustered, LOC receptive fields (RFs) were large and bilateral, and a number of LOC neurons exhibited three-dimensional (3D)-structure selectivity (a preference for convex or concave stimuli), which are all properties typical of end-stage ventral stream areas. Thus, our results challenge prevailing ideas about the position of the more posterior subsector of LOC in the hierarchy of visual areas.

Effective Connectivity Reveals an Interconnected Inferotemporal Network for Three-Dimensional Structure Processing.

Disparity-defined 3D shape is processed in both the ventral and the dorsal visual stream. The network of cortical areas that is activated during the processing of disparity-defined 3D shape includes, in addition to parietal and premotor areas, three clearly distinct regions in inferotemporal cortex (ITC). To investigate the connectivity of the latter regions, we combined electrical stimulation with fMRI in male macaque monkeys. Electrical stimulation of each of the 3D-structure nodes in ITC mainly elicited increased fMRI activations in the other 3D-structure nodes and more variably in other parts of ventral visual cortex. Importantly, no increased activation was found in parietal areas, nor in PFC, whereas microstimulation in posterior parietal cortex did activate the ITC. Our results indicate that 3D-structure nodes in ITC form a strongly interconnected network, receiving input from parietal areas implicated in 3D-structure processing.SIGNIFICANCE STATEMENT Previous studies combining electrical microstimulation with functional imaging showed an interconnected set of regions in the ventral stream processing faces or bodies, but is has been unclear whether the same is true for other visual categories. Here the authors show that there is a connected system of stereo-selective regions in inferotemporal cortex, receiving input from parietal areas in the dorsal stream.

Temporal dynamics of neural activity in macaque frontal cortex assessed with large-scale recordings.

The cortical network controlling the arm and hand when grasping objects consists of several areas in parietal and frontal cortex. Recently, more anterior prefrontal areas have also been implicated in object grasping, but their exact role is currently unclear. To investigate the neuronal encoding of objects during grasping in these prefrontal regions and their relation with other cortical areas of the grasping network, we performed large-scale recordings (more than 2000 responsive sites) in frontal cortex of monkeys during a saccade-reach-grasp task. When an object appeared in peripheral vision, the first burst of activity emerged in prearcuate areas (the FEF and area 45B), followed by dorsal and ventral premotor cortex, and a buildup of activity in primary motor cortex. After the saccade, prearcuate activity remained elevated while primary motor and premotor activity rose in anticipation of the upcoming arm and hand movement. Remarkably, a large number of premotor and prearcuate sites responded when the object appeared in peripheral vision and remained active when the object came into foveal vision. Thus, prearcuate and premotor areas continuously encode object information when directing gaze and grasping objects.

Functional MRI in Macaque Monkeys during Task Switching.

Nonhuman primates have proven to be a valuable animal model for exploring neuronal mechanisms of cognitive control. One important aspect of executive control is the ability to switch from one task to another, and task-switching paradigms have often been used in human volunteers to uncover the underlying neuronal processes. To date, however, no study has investigated task-switching paradigms in nonhuman primates during functional magnetic resonance imaging (fMRI). We trained two rhesus macaques to switch between arm movement, eye movement, and passive fixation tasks during fMRI. Similar to results obtained in human volunteers, task switching elicits increased fMRI activations in prefrontal cortex, anterior cingulate cortex, orbitofrontal cortex, and caudate nucleus. Our results indicate that the macaque monkey is a reliable model with which to investigate higher-order cognitive functioning such as task switching. As such, these results can pave the way for a detailed investigation of the neural basis of complex human behavior.SIGNIFICANCE STATEMENT Task switching is an important aspect of cognitive control, and task-switching paradigms have often been used to investigate higher-order executive functioning in human volunteers. We used a task-switching paradigm in the nonhuman primate during fMRI and found increased activation mainly in prefrontal areas (46, 45, frontal eye field, and anterior cingulate), in orbitofrontal area 12, and in the caudate nucleus. These data fit surprisingly well with previous human imaging data, proving that the monkey is an excellent model to study task switching with high spatiotemporal resolution tools that are currently not applicable in humans. As such, our results pave the way for a detailed interrogation of regions performing similar executive functions in humans and monkeys.

Posterior Parietal Cortex Drives Inferotemporal Activations During Three-Dimensional Object Vision.

The primate visual system consists of a ventral stream, specialized for object recognition, and a dorsal visual stream, which is crucial for spatial vision and actions. However, little is known about the interactions and information flow between these two streams. We investigated these interactions within the network processing three-dimensional (3D) object information, comprising both the dorsal and ventral stream. Reversible inactivation of the macaque caudal intraparietal area (CIP) during functional magnetic resonance imaging (fMRI) reduced fMRI activations in posterior parietal cortex in the dorsal stream and, surprisingly, also in the inferotemporal cortex (ITC) in the ventral visual stream. Moreover, CIP inactivation caused a perceptual deficit in a depth-structure categorization task. CIP-microstimulation during fMRI further suggests that CIP projects via posterior parietal areas to the ITC in the ventral stream. To our knowledge, these results provide the first causal evidence for the flow of visual 3D information from the dorsal stream to the ventral stream, and identify CIP as a key area for depth-structure processing. Thus, combining reversible inactivation and electrical microstimulation during fMRI provides a detailed view of the functional interactions between the two visual processing streams.

Caudal Intraparietal Sulcus and three-dimensional vision: A combined functional magnetic resonance imaging and single-cell study.

The cortical network processing three-dimensional (3D) object structure defined by binocular disparity spans both the ventral and dorsal visual streams. However, very little is known about the neural representation of 3D structure at intermediate levels of the visual hierarchy. Here, we investigated the neural selectivity for 3D surfaces in the macaque Posterior Intraparietal area (PIP) in the medial bank of the caudal intraparietal sulcus (IPS). We first identified a region sensitive to depth-structure information in the medial bank of the caudal IPS using functional Magnetic Resonance Imaging (fMRI), and then recorded single-cell activity within this fMRI activation in the same animals. Most PIP neurons were selective for the 3D orientation of planar surfaces (first-order disparity) at very short latencies, whereas a very small fraction of PIP neurons were selective for curved surfaces (second-order disparity). A linear support vector machine classifier could reliably identify the direction of the disparity gradient in planar and curved surfaces based on the responses of a population of disparity-selective PIP neurons. These results provide the first detailed account of the neuronal properties in area PIP, which occupies an intermediate position in the hierarchy of visual areas involved in processing depth structure from disparity.

Shape responses in a macaque frontal area connected to posterior parietal cortex.

The primate dorsal visual stream processes object shape to guide actions involving an object, but the transmission of shape information beyond posterior parietal cortex remains largely unknown. To clarify the information flow between parietal and frontal cortex, we applied electrical microstimulation during functional Magnetic Resonance Imaging (fMRI) in a shape-selective patch in the posterior part of the Anterior Intraparietal area (pAIP) to chart its connectivity. Subsequently, we recorded single-unit responses to images of objects in the fMRI activation in prefrontal cortex, corresponding to area 45B, elicited by pAIP microstimulation. Neurons in area 45B had properties similar to neurons in pAIP, responding selectively to shape contours and to very small shape fragments measuring less than one deg at exceedingly short latencies. However, contrary to the prevailing view on the hierarchical organization of cortical areas, neurons in area 45B preferred even smaller shape fragments and had smaller receptive fields than neurons in pAIP. These findings provide the first evidence for ultra-fast shape processing in prefrontal cortex, and suggest that the pathway from pAIP to area 45B may not be important for object grasping.

Single-cell responses to three-dimensional structure in a functionally defined patch in macaque area TEO.

Both dorsal and ventral visual pathways harbor several areas sensitive to gradients of binocular disparity (i.e., higher-order disparity). Although a wealth of information exists about disparity processing in early visual (V1, V2, and V3) and end-stage areas, TE in the ventral stream, and the anterior intraparietal area (AIP) in the dorsal stream, little is known about midlevel area TEO in the ventral pathway. We recorded single-unit responses to disparity-defined curved stimuli in a functional magnetic resonance imaging (fMRI) activation elicited by curved surfaces compared with flat surfaces in the macaque area TEO. This fMRI activation contained a small proportion of disparity-selective neurons, with very few of them second-order disparity selective. Overall, this population of TEO neurons did not preserve its three-dimensional structure selectivity across positions in depth, indicating a lack of higher-order disparity selectivity, but showed stronger responses to flat surfaces than to curved surfaces, as predicted by the fMRI experiment. The receptive fields of the responsive TEO cells were relatively small and generally foveal. A linear support vector machine classifier showed that this population of disparity-selective TEO neurons contains reliable information about the sign of curvature and the position in depth of the stimulus. NEW & NOTEWORTHY We recorded in a part of the macaque area TEO that is activated more by curved surfaces than by flat surfaces at different disparities using the same stimuli. In contrast to previous studies, this functional magnetic resonance imaging-defined patch did not contain a large number of higher-order disparity-selective neurons. However, a linear support vector machine could reliably classify both the sign of the disparity gradient and the position in depth of the stimuli.

Positron emission tomography imaging of cerebral glucose metabolism and type 1 cannabinoid receptor availability during temporal lobe epileptogenesis in the amygdala kindling model in rhesus monkeys.

OBJECTIVE: We investigated changes in the endocannabinoid system and glucose metabolism during temporal lobe epileptogenesis. METHODS: Because it is rarely possible to study epileptogenesis in humans, we applied the electrical amygdala kindling model in nonhuman primates to image longitudinal changes in type 1 cannabinoid receptor (CB1R) binding and cerebral glucose metabolism. Two rhesus monkeys received [18 F]-MK-9470 and fluorodeoxyglucose-positron emission tomography ([18 F]-FDG -PET) scans in each of the 4 kindling stages to quantify relative changes over time of CB1R binding and cerebral glucose metabolism in vivo. We constructed z-score images relative to a control group (n = 8), and considered only those changes measured in both kindled animals by calculating the binary conjunction image per kindling stage. RESULTS: The seizure-onset zone exhibited an increased CB1R binding and a decreased glucose metabolism, which both aggravated gradually in extent and intensity throughout kindling. The ipsilateral thalamus and insula showed hypometabolism that coincided with an increase and a decrease in CB1R binding, respectively. These changes also became gradually more severe throughout kindling and overlapped with ictal perfusion changes during the final stage of amygdala kindling, with hyperperfusion in the ipsilateral thalamus and hypoperfusion in the ipsilateral insula. SIGNIFICANCE: The observed changes in CB1R binding may reflect a combination of a protective mechanism of neurons against seizure activity that becomes stronger over time to combat more severe seizures, and on the other hand, a process of epileptogenesis that facilitates seizure activity and generalization, depending on the cell type involved in those specific regions. This study provides unique evidence that the CB1R is dynamically and progressively involved from the start of mesial temporal lobe epileptogenesis.