A chinrest-based approach to measure eye movements and experimental task engagement in macaques with minimal restraint.

BACKGROUND: The use of Rhesus macaques in vision research is crucial due to their visual system's similarity to humans. While invasive techniques have been the norm, there has been a shift towards non-invasive methods, such as facemasks and head molds, to enhance animal welfare and address ethical concerns. NEW METHOD: We present a non-invasive, 3D-printed chinrest with infrared sensors, adapted from canine research, allowing for accurate eye movement measurements and voluntary animal participation in experiments. RESULTS: The chinrest method showed a 16% and 28% increase in average trial numbers for Monkey 1 and Monkey 2, respectively, compared to the traditional headpost method. The engagement was high, with monkeys performing over 500 trials per session and initiating a new trial after an average intertrial interval of approximately 1 second. The hit rate improved by about 10% for Monkey 1 in the chinrest condition, and the fixation precision, measured by the standard deviation of gaze positions, was significantly better in the chinrest condition, with Monkey 1 showing a reduction in fixation imprecision from 0.26° to 0.17° in the X-axis. COMPARISON WITH EXISTING METHODS: The chinrest approach showed significant improvements in trial engagement and reduction in aborted trials due to fixation breaks, indicating less stress and potentially improved data quality compared to previous non-invasive methods. CONCLUSIONS: The chinrest method offers a significant advancement in primate cognitive testing by allowing for precise data collection while addressing animal welfare concerns, possibly leading to better scientific outcomes and a paradigm shift in primate research methodologies.

Optogenetic stimulation of the primary visual cortex drives activity in the visual association cortex.

Developing optogenetic methods for research in non-human primates (NHP) is important for translational neuroscience and for delineating brain function with unprecedented specificity. Here we assess, in macaque monkeys, the selectivity by which optogenetic stimulation of the primary visual cortex (V1) drives the local laminar and widespread cortical connectivity related to visual perception. Towards this end, we transfected neurons with light-sensitive channelrhodopsin in dorsal V1. fMRI revealed that optogenetic stimulation of V1 using blue light at 40 Hz increased functional activity in the visual association cortex, including areas V2/V3, V4, motion-sensitive area MT and frontal eye fields, although nonspecific heating and eye movement contributions to this effect could not be ruled out. Neurophysiology and immunohistochemistry analyses confirmed optogenetic modulation of spiking activity and opsin expression with the strongest expression in layer 4-B in V1. Stimulating this pathway during a perceptual decision task effectively elicited a phosphene percept in the receptive field of the stimulated neurons in one monkey. Taken together, our findings demonstrate the great potential of optogenetic methods to drive the large-scale cortical circuits of the primate brain with high functional and spatial specificity.

Reading Specific Small Saccades Predict Individual Phonemic Awareness and Reading Speed.

Small fixational eye-movements are a fundamental aspect of vision and thought to reflect fine shifts in covert attention during active viewing. While the perceptual benefits of these small eye movements have been demonstrated during a wide range of experimental tasks including during free viewing, their function during reading remains surprisingly unclear. Previous research demonstrated that readers with increased microsaccade rates displayed longer reading speeds. To what extent increased fixational eye movements are, however, specific to reading and might be indicative of reading skill deficits remains, however, unknown. To address this topic, we compared the eye movement scan paths of 13 neurotypical individuals and 13 subjects diagnosed with developmental dyslexia during short story reading and free viewing of natural scenes. We found that during reading only, dyslexics tended to display small eye movements more frequently compared to neurotypicals, though this effect was not significant at the population level, as it could also occur in slow readers not diagnosed as dyslexics. In line with previous research, neurotypical readers had twice as many regressive compared to progressive microsaccades, which did not occur during free viewing. In contrast, dyslexics showed similar amounts of regressive and progressive small fixational eye movements during both reading and free viewing. We also found that participants with smaller fixational saccades from both neurotypical and dyslexic samples displayed reduced reading speeds and lower scores during independent tests of reading skill. Slower readers also displayed greater variability in the landing points and temporal occurrence of their fixational saccades. Both the rate and spatio-temporal variability of fixational saccades were associated with lower phonemic awareness scores. As none of the observed differences between dyslexics and neurotypical readers occurred during control experiments with free viewing, the reported effects appear to be directly related to reading. In summary, our results highlight the predictive value of small saccades for reading skill, but not necessarily for developmental dyslexia.

Wide-field retinotopy reveals a new visuotopic cluster in macaque posterior parietal cortex.

We investigated the visuotopic organization of macaque posterior parietal cortex (PPC) by combining functional imaging (fMRI) and wide-field retinotopic mapping in two macaque monkeys. Whole brain blood-oxygen-level-dependent (BOLD) signal was recorded while monkeys maintained central fixation during the presentation of large rotating wedges and expending/contracting annulus of a "shaking" fruit basket, designed to maximize the recruitment of PPC neurons. Results of the surface-based population receptive field (pRF) analysis reveal a new cluster of four visuotopic areas at the confluence of the parieto-occipital and intra-parietal sulci, in a location previously defined histologically and anatomically as the posterior intra-parietal (PIP) region. This PIP cluster groups together two recently described areas (CIP1/2) laterally and two newly identified ones (PIP1/2) medially, whose foveal representations merge in the fundus of the intra-parietal sulcus. The cluster shares borders with other visuotopic areas: V3d posteriorly, V3A/DP laterally, V6/V6A medially and LIP anteriorly. Together, these results show that monkey PPC is endowed with a dense set of visuotopic areas, as its human counterpart. The fact that fMRI and wide-field stimulation allows a functional parsing of monkey PPC offers a new framework for studying functional homologies with human PPC.

Stereomotion Processing in the Nonhuman Primate Brain.

The cortical areas that process disparity-defined motion-in-depth (i.e., cyclopean stereomotion [CSM]) were characterized with functional magnetic resonance imaging (fMRI) in two awake, behaving macaques. The experimental protocol was similar to previous human neuroimaging studies. We contrasted the responses to dynamic random-dot patterns that continuously changed their binocular disparity over time with those to a control condition that shared the same properties, except that the temporal frames were shuffled. A whole-brain voxel-wise analysis revealed that in all four cortical hemispheres, three areas showed consistent sensitivity to CSM. Two of them were localized respectively in the lower bank of the superior temporal sulcus (CSMSTS) and on the neighboring infero-temporal gyrus (CSMITG). The third area was situated in the posterior parietal cortex (CSMPPC). Additional regions of interest-based analyses within retinotopic areas defined in both animals indicated weaker but significant responses to CSM within the MT cluster (most notably in areas MSTv and FST). Altogether, our results are in agreement with previous findings in both human and macaque and suggest that the cortical areas that process CSM are relatively well preserved between the two primate species.

Advantage of detecting visual events in the right hemifield is affected by reading skill.

Visual perception is often not homogenous across the visual field and can vary depending on situational demands. The reasons behind this inhomogeneity are not clear. Here we show that directing attention that is consistent with a western reading habit from left to right, results in a ~32% higher sensitivity to detect transient visual events in the right hemifield. This right visual field advantage was largely reduced in individuals with reading difficulties from developmental dyslexia. Similarly, visual detection became more symmetric in skilled readers, when attention was guided opposite to the reading pattern. Taken together, these findings highlight a higher sensitivity in the right visual field for detecting the onset of sudden visual events that is well accounted for by left hemisphere dominated reading habit.

Asymmetry of pictorial space: A cultural phenomenon.

Art experts have argued that the mirror reversal of pictorial artworks produces an alteration of their spatial content. However, this putative asymmetry of the pictorial space remains to be empirically proved and causally explained. Here, we address these issues with the "corridor illusion," a size illusion triggered by the pictorial space of a receding corridor. We show that mirror-reversed corridors-receding respectively leftward and rightward-induce markedly different illusion strengths and thus convey distinct pictorial spaces. Remarkably, the illusion is stronger with the rightward corridor among native left-to-right readers (French participants, n = 40 males) but conversely stronger with the leftward corridor among native right-to-left readers (Syrian participants, n = 40 males). Together, these results demonstrate an asymmetry of the pictorial space and point to our reading/writing habits as a major cause of this phenomenon.

Rewarding objects appear larger but not brighter.

Whether reward can accentuate the perception of visual objects, that is, makes them appear larger than they really are, is a long-standing and controversial question. Here, we revisit this issue with a novel two-alternative forced-choice paradigm combining asymmetric reward schedule and task reversal. In a first experiment, participants (n = 27) choose the larger of two unequally rewarded objects in some sessions and the smaller one in other sessions. Response biases toward the most rewarding object differ significantly between the reversed tasks, revealing an influence of reward on perceived sizes. In a second experiment, participants (n = 27) indicate either the brighter or darker object. In contrast with the first experiment, response biases are similar between those reversed tasks, indicating that the perceived luminance is immune to reward manipulation. Together, these results reveal that if two objects are associated with different amounts of reward, participants will perceive the more rewarded object to be slightly larger, but not brighter, than the less rewarded one.

Processing of Egomotion-Consistent Optic Flow in the Rhesus Macaque Cortex.

The cortical network that processes visual cues to self-motion was characterized with functional magnetic resonance imaging in 3 awake behaving macaques. The experimental protocol was similar to previous human studies in which the responses to a single large optic flow patch were contrasted with responses to an array of 9 similar flow patches. This distinguishes cortical regions where neurons respond to flow in their receptive fields regardless of surrounding motion from those that are sensitive to whether the overall image arises from self-motion. In all 3 animals, significant selectivity for egomotion-consistent flow was found in several areas previously associated with optic flow processing, and notably dorsal middle superior temporal area, ventral intra-parietal area, and VPS. It was also seen in areas 7a (Opt), STPm, FEFsem, FEFsac and in a region of the cingulate sulcus that may be homologous with human area CSv. Selectivity for egomotion-compatible flow was never total but was particularly strong in VPS and putative macaque CSv. Direct comparison of results with the equivalent human studies reveals several commonalities but also some differences.

Role of the primate ventral tegmental area in reinforcement and motivation.

Monkey electrophysiology suggests that the activity of the ventral tegmental area (VTA) helps regulate reinforcement learning and motivated behavior, in part by broadcasting prediction error signals throughout the reward system. However, electrophysiological studies do not allow causal inferences regarding the activity of VTA neurons with respect to these processes because they require artificial manipulation of neuronal firing. Rodent studies fulfilled this requirement by demonstrating that electrical and optogenetic VTA stimulation can induce learning and modulate downstream structures. Still, the primate dopamine system has diverged significantly from that of rodents, exhibiting greatly expanded and uniquely distributed cortical and subcortical innervation patterns. Here, we bridge the gap between rodent perturbation studies and monkey electrophysiology using chronic electrical microstimulation of macaque VTA (VTA-EM). VTA-EM was found to reinforce cue selection in an operant task and to motivate future cue selection using a Pavlovian paradigm. Moreover, by combining VTA-EM with concurrent fMRI, we demonstrated that VTA-EM increased fMRI activity throughout most of the dopaminergic reward system. These results establish a causative role for primate VTA in regulating stimulus-specific reinforcement and motivation as well as in modulating activity throughout the reward system.