Always expect the unexpected: Eye position modulates visual cortex excitability in a stimulus-free environment.

BACKGROUND: Stimuli that potentially require a rapid defensive or avoidance action can appear from the periphery at any time in natural environments. De Wit, Faseyitan, and Coslett (2020) recently reported novel evidence suggestive of a fundamental neural mechanism that allows organisms to effectively deal with such situations. In the absence of any task, motor cortex excitability was found to be greater whenever gaze was directed away from either hand. OBJECTIVE/HYPOTHESIS: If modulation of cortical excitability as a function of gaze location is a fundamental principle of brain organization, then one would expect its operation to be present also outside of motor cortex, such as brain regions involved in perception. METHODS: To test this hypothesis, we applied single-pulse transcranial magnetic stimulation (TMS) to the right lateral occipital lobe while participants directed their eyes to the left, straight ahead, or to the right, and reported the presence or absence of a phosphene. No external stimuli were presented. RESULTS: Cortical excitability as reflected by phosphene threshold was greater with eyes deviated to the right as compared to the left. CONCLUSION: In conjunction with our previous findings of upregulation of motor cortex excitability when gaze and effector are not aligned, this eye position-driven increase in visual cortex excitability presumably serves to facilitate the detection of stimuli and subsequent readiness to act in non-foveated regions of space. The existence of this brain-wide mechanism has clear adaptive value given the unpredictable nature of natural environments in which human beings are situated and have evolved.

Ocular dominance-dependent binocular combination of monocular neuronal responses in macaque V1.

Primates rely on two eyes to perceive depth, while maintaining stable vision when either one eye or both eyes are open. Although psychophysical and modeling studies have investigated how monocular signals are combined to form binocular vision, the underlying neuronal mechanisms, particularly in V1 where most neurons exhibit binocularity with varying eye preferences, remain poorly understood. Here, we used two-photon calcium imaging to compare the monocular and binocular responses of thousands of simultaneously recorded V1 superficial-layer neurons in three awake macaques. During monocular stimulation, neurons preferring the stimulated eye exhibited significantly stronger responses compared to those preferring both eyes. However, during binocular stimulation, the responses of neurons preferring either eye were suppressed on the average, while those preferring both eyes were enhanced, resulting in similar neuronal responses irrespective of their eye preferences, and an overall response level similar to that with monocular viewing. A neuronally realistic model of binocular combination, which incorporates ocular dominance-dependent divisive interocular inhibition and binocular summation, is proposed to account for these findings.

M2 receptors are required for spatiotemporal sequence learning in mouse primary visual cortex.

Acetylcholine is a neurotransmitter that plays a variety of roles in the central nervous system. It was previously shown that blocking muscarinic receptors with a non-selective antagonist prevents a form of experience-dependent plasticity termed "spatiotemporal sequence learning" in the mouse primary visual cortex (V1). Muscarinic signaling is a complex process involving the combined activities of five different G-protein coupled receptors, M1-M5, all of which are expressed in the murine brain but differ from each other functionally and in anatomical localization. Here we present electrophysiological evidence that M2, but not M1, receptors are required for spatiotemporal sequence learning in mouse V1. We show in male mice that M2 is highly expressed in the neuropil in V1, especially in thalamorecipient layer 4, and co-localizes with the soma in a subset of somatostatin expressing neurons in deep layers. We also show that expression of M2 receptors is higher in the monocular region of V1 than it is in the binocular region, but that the amount of experience-dependent sequence potentiation is similar in both regions, and that blocking muscarinic signaling after visual stimulation does not prevent plasticity. This work establishes a new functional role for M2-type receptors in processing temporal information and demonstrates that monocular circuits are modified by experience in a manner similar to binocular circuits.

Two what, two where, visual cortical streams in humans.

ROLLS, E. T. Two What, Two Where, Visual Cortical Streams in Humans. NEUROSCI BIOBEHAV REV 2024. Recent cortical connectivity investigations lead to new concepts about 'What' and 'Where' visual cortical streams in humans, and how they connect to other cortical systems. A ventrolateral 'What' visual stream leads to the inferior temporal visual cortex for object and face identity, and provides 'What' information to the hippocampal episodic memory system, the anterior temporal lobe semantic system, and the orbitofrontal cortex emotion system. A superior temporal sulcus (STS) 'What' visual stream utilising connectivity from the temporal and parietal visual cortex responds to moving objects and faces, and face expression, and connects to the orbitofrontal cortex for emotion and social behaviour. A ventromedial 'Where' visual stream builds feature combinations for scenes, and provides 'Where' inputs via the parahippocampal scene area to the hippocampal episodic memory system that are also useful for landmark-based navigation. The dorsal 'Where' visual pathway to the parietal cortex provides for actions in space, but also provides coordinate transforms to provide inputs to the parahippocampal scene area for self-motion update of locations in scenes in the dark or when the view is obscured.

Immunocytochemical localization of nitric oxide synthase-containing neurons in the visual cortex of the Mongolian gerbil.

INTRODUCTION: Nitric oxide (NO) is present in various cell types in the central nervous system and plays a crucial role in the control of various cellular functions. The diurnal Mongolian gerbil is a member of the rodent family Muridae that exhibits unique physiological, anatomical, and behavioral differences from the nocturnal rat and mouse, which render it a useful model for studying the visual system. The purpose of this study was to confirm the distribution and morphology of neurons that contain nitric oxide synthase (NOS) and their pattern of co-expressing NOS with neuropeptide Y (NPY), somatostatin (SST), and gamma-aminobutyric acid (GABA) in the visual cortex of Mongolian gerbils. MATERIALS AND METHODS: Mongolian gerbils were used in the study. We confirmed the localization of NOS in the visual cortex of Mongolian gerbils using horseradish peroxidase immunocytochemistry, fluorescent immunocytochemistry, and conventional confocal microscopy. RESULTS: NOS-immunoreactive (IR) neurons were present in all layers of the visual cortex of the Mongolian gerbil, with the exception of layer I, with the highest density observed in layer V (50.00%). The predominant type of NOS-IR neurons was multipolar round/oval cells (60.96%). Two-color immunofluorescence revealed that 100% NOS-IR neurons were co-labeled with NPY and SST and 34.55% were co-labeled with GABA. CONCLUSIONS: Our findings of the laminar distribution and morphological characteristics of NOS-IR neurons, as well as the colocalization patterns of NOS-IR neurons with NPY, SST, and GABA, indicated the presence of species-specific differences, suggesting the functional diversity of NO in the visual cortex. This study provides valuable data on the anatomical organization of NOS-IR neurons and, consequently, a better understanding of the functional aspects of NO and species diversity.

Effects of environmental enrichment on GLUT expression in the visual cortex of amblyopic rats.

OBJECTIVE: To investigate the potential changes of glucose metabolism and glucose transporter protein (GLUT) in the visual cortex of formally deprived amblyopic rats, as well as the effects of enriched environments on the levels of nerve conduction and glucose metabolism in the visual cortex of amblyopic rats. METHODS: 36 rats were randomly divided into three groups: CON + SE (n = 12), MD + SE (n = 12) and MD + EE (n = 12). The right eyelids of both MD + SE and MD + EE groups were sutured. After successful modelling, the MD + EE group was maintained in an enriched environment, and the other two groups were kept in the same environment. Pattern visual evoked potentials (PVEP) was used to confirm models' effect, glucose metabolism was analyzed by Micro-PET/CT (18F-FDG), and the protein as well as mRNA expression levels of GLUT were detected by Western Blot and quantitative RT-PCR (quantitative Reverse Transcription-Polymerase Chain Reaction) analyses, site of GLUT expression by immunofluorescence (IF). RESULTS: After suture modelling, both the MD + EE and MD + SE groups objective visual nerve conduction function decreased, the glucose metabolism in the visual cortex was markedly lower. After the enriched environment intervention, it recovered in the MD + EE group. The expression levels of GLUT1 and GLUT3 were increased in the MD + EE group in comparison with the MD + SE group. GLUT1 was primarily expressed on astrocytes and endothelial cells, but GLUT3 was mainly expressed on neurons. CONCLUSION: Enrichment of the environment exhibited a therapeutic effect on amblyopia, which could be related to the enhancement of glucose metabolism and GLUT expression in the visual cortex.

Encoding luminance surfaces in the visual cortex of mice and monkeys: difference in responses to edge and center.

Luminance and spatial contrast provide information on the surfaces and edges of objects. We investigated neural responses to black and white surfaces in the primary visual cortex (V1) of mice and monkeys. Unlike primates that use their fovea to inspect objects with high acuity, mice lack a fovea and have low visual acuity. It thus remains unclear whether monkeys and mice share similar neural mechanisms to process surfaces. The animals were presented with white or black surfaces and the population responses were measured at high spatial and temporal resolution using voltage-sensitive dye imaging. In mice, the population response to the surface was not edge-dominated with a tendency to center-dominance, whereas in monkeys the response was edge-dominated with a "hole" in the center of the surface. The population response to the surfaces in both species exhibited suppression relative to a grating stimulus. These results reveal the differences in spatial patterns to luminance surfaces in the V1 of mice and monkeys and provide evidence for a shared suppression process relative to grating.

Visual omitted stimulus potentials are not retinotopic.

Omitted stimulus potentials (OSPs) are elicited in response to the omission of expected stimuli and are thought to reflect prediction errors. If prediction errors are signaled in the sensory cortex, OSPs are expected to be generated in the sensory cortex. The present study investigated the involvement of the early visual cortex in the generation of OSPs by testing whether omitted visual stimuli elicit brain responses in a spatially specific manner. Checkerboard pattern stimuli were presented alternately in the upper and lower visual fields, and the stimuli were omitted in 10 % of the trials. Event-related potentials were recorded from 33 participants. While a retinotopic C1 component was evoked by real visual stimuli, omitted stimuli did not produce any response reflecting retinotopy but did elicit a visual mismatch negativity, which was larger for omitted stimuli expected in the lower visual field than for those in the upper visual field. These results suggest that omitted visual stimuli are processed in a different pathway than actual stimuli.

Stimulus-dependent differences in cortical versus subcortical contributions to visual detection in mice.

The primary visual cortex (V1) and the superior colliculus (SC) both occupy stations early in the processing of visual information. They have long been thought to perform distinct functions, with the V1 supporting the perception of visual features and the SC regulating orienting to visual inputs. However, growing evidence suggests that the SC supports the perception of many of the same visual features traditionally associated with the V1. To distinguish V1 and SC contributions to visual processing, it is critical to determine whether both areas causally contribute to the detection of specific visual stimuli. Here, mice reported changes in visual contrast or luminance near their perceptual threshold while white noise patterns of optogenetic stimulation were delivered to V1 or SC inhibitory neurons. We then performed a reverse correlation analysis on the optogenetic stimuli to estimate a neuronal-behavioral kernel (NBK), a moment-to-moment estimate of the impact of V1 or SC inhibition on stimulus detection. We show that the earliest moments of stimulus-evoked activity in the SC are critical for the detection of both luminance and contrast changes. Strikingly, there was a robust stimulus-aligned modulation in the V1 contrast-detection NBK but no sign of a comparable modulation for luminance detection. The data suggest that behavioral detection of visual contrast depends on both V1 and SC spiking, whereas mice preferentially use SC activity to detect changes in luminance. Electrophysiological recordings showed that neurons in both the SC and V1 responded strongly to both visual stimulus types, while the reverse correlation analysis reveals when these neuronal signals actually contribute to visually guided behaviors.

Modular horizontal network within mouse primary visual cortex.

Interactions between feedback connections from higher cortical areas and local horizontal connections within primary visual cortex (V1) were shown to play a role in contextual processing in different behavioral states. Layer 1 (L1) is an important part of the underlying network. This cell-sparse layer is a target of feedback and local inputs, and nexus for contacts onto apical dendrites of projection neurons in the layers below. Importantly, L1 is a site for coupling inputs from the outside world with internal information. To determine whether all of these circuit elements overlap in L1, we labeled the horizontal network within mouse V1 with anterograde and retrograde viral tracers. We found two types of local horizontal connections: short ones that were tangentially limited to the representation of the point image, and long ones which reached beyond the receptive field center, deep into its surround. The long connections were patchy and terminated preferentially in M2 muscarinic acetylcholine receptor-negative (M2-) interpatches. Anterogradely labeled inputs overlapped in M2-interpatches with apical dendrites of retrogradely labeled L2/3 and L5 cells, forming module-selective loops between topographically distant locations. Previous work showed that L1 of M2-interpatches receive inputs from the lateral posterior thalamic nucleus (LP) and from a feedback network from areas of the medial dorsal stream, including the secondary motor cortex. Together, these findings suggest that interactions in M2-interpatches play a role in processing visual inputs produced by object-and self-motion.

When perception fades, the hippocampus may support implicit memory.

Steinkrauss and Slotnick (2024) conclude that current evidence is insufficient to sustain a link between implicit memory and the hippocampus. However, behavioral protocols designed to minimize visual awareness, so that memoranda are objectively invisible both at study and at test, can yield brain-based signals of implicit memory, which circumvent several of the identified constraints. Furthermore, while differences in novelty and attention complicate the interpretation of hippocampal involvement in implicit memory tasks, these processes can occur with and without conscious awareness, suggesting a more complex interplay between the hippocampus and memory-related processes than an exclusive association with consciousness would indicate.

Stimulus-dependent synaptic plasticity underlies neuronal circuitry refinement in the mouse primary visual cortex.

Perceptual learning improves our ability to interpret sensory stimuli present in our environment through experience. Despite its importance, the underlying mechanisms that enable perceptual learning in our sensory cortices are still not fully understood. In this study, we used in vivo two-photon imaging to investigate the functional and structural changes induced by visual stimulation in the mouse primary visual cortex (V1). Our results demonstrate that repeated stimulation leads to a refinement of V1 circuitry by decreasing the number of responsive neurons while potentiating their response. At the synaptic level, we observe a reduction in the number of dendritic spines and an overall increase in spine AMPA receptor levels in the same subset of neurons. In addition, visual stimulation induces synaptic potentiation in neighboring spines within individual dendrites. These findings provide insights into the mechanisms of synaptic plasticity underlying information processing in the neocortex.

Are we aware of neural activity in primary visual cortex? A neuropsychological case study.

OBJECTIVE: According to a seminal hypothesis stated by Crick and Koch in 1995, one is not aware of neural activity in primary visual cortex (V1) because this region lacks reciprocal connections with prefrontal cortex (PFC). METHODS: We provide here a neuropsychological illustration of this hypothesis in a patient with a very rare form of cortical blindness: ventral and dorsal cortical pathways were lesioned bilaterally while V1 areas were partially preserved. RESULTS: Visual stimuli escaped conscious perception but still activated V1 regions that were functionally disconnected from PFC. INTERPRETATION: These results are consistent with the hypothesis of a causal role of PFC in visual awareness.

Parallel Streams of Direct Corticogeniculate Feedback from Mid-level Extrastriate Cortex in the Macaque Monkey.

First-order thalamic nuclei receive feedforward signals from peripheral receptors and relay these signals to primary sensory cortex. Primary sensory cortex, in turn, provides reciprocal feedback to first-order thalamus. Because the vast majority of sensory thalamocortical inputs target primary sensory cortex, their complementary corticothalamic neurons are assumed to be similarly restricted to primary sensory cortex. We upend this assumption by characterizing morphologically diverse neurons in multiple mid-level visual cortical areas of the primate (Macaca mulatta) brain that provide direct feedback to the primary visual thalamus, the dorsal lateral geniculate nucleus (LGN). Although the majority of geniculocortical neurons project to primary visual cortex (V1), a minority, located mainly in the koniocellular LGN layers, provide direct input to extrastriate visual cortex. These "V1-bypassing" projections may be implicated in blindsight. We hypothesized that geniculocortical inputs directly targeting extrastriate cortex should be complemented by reciprocal corticogeniculate circuits. Using virus-mediated circuit tracing, we discovered corticogeniculate neurons throughout three mid-level extrastriate areas: MT, MST, and V4. Quantitative morphological analyses revealed nonuniform distributions of unique cell types across areas. Many extrastriate corticogeniculate neurons had spiny stellate morphology, suggesting possible targeting of koniocellular LGN layers. Importantly though, multiple morphological types were observed across areas. Such morphological diversity could suggest parallel streams of V1-bypassing corticogeniculate feedback at multiple stages of the visual processing hierarchy. Furthermore, the presence of corticogeniculate neurons across visual cortex necessitates a reevaluation of the LGN as a hub for visual information rather than a simple relay.

Bypassing input to V1 in visual awareness: A TMS-EROS investigation.

Early visual cortex (V1-V3) is believed to be critical for normal visual awareness by providing the necessary feedforward input. However, it remains unclear whether visual awareness can occur without further involvement of early visual cortex, such as re-entrant feedback. It has been challenging to determine the importance of feedback activity to these areas because of the difficulties in dissociating this activity from the initial feedforward activity. Here, we applied single-pulse transcranial magnetic stimulation (TMS) over the left posterior parietal cortex to elicit phosphenes in the absence of direct visual input to early visual cortex. Immediate neural activity after the TMS pulse was assessed using the event-related optical signal (EROS), which can measure activity under the TMS coil without artifacts. Our results show that: 1) The activity in posterior parietal cortex 50 ms after TMS was related to phosphene awareness, and 2) Activity related to awareness was observed in a small portion of V1 140 ms after TMS, but in contrast (3) Activity in V2 was a more robust correlate of awareness. Together, these results are consistent with interactive models proposing that sustained and recurrent loops of activity between cortical areas are necessary for visual awareness to emerge. In addition, we observed phosphene-related activations of the anteromedial cuneus and lateral occipital cortex, suggesting a functional network subserving awareness comprising these regions, the parietal cortex and early visual cortex.

In primary visual cortex fMRI responses to chromatic and achromatic stimuli are interdependent and predict contrast detection thresholds.

Chromatic and achromatic signals in primary visual cortex have historically been considered independent of each other but have since shown evidence of interdependence. Here, we investigated the combination of two components of a stimulus; an achromatic dynamically changing check background and a chromatic (L-M or S cone) target grating. We found that combinations of chromatic and achromatic signals in primary visual cortex were interdependent, with the dynamic range of responses to chromatic contrast decreasing as achromatic contrast increased. A contrast detection threshold study also revealed interdependence of background and target, with increasing chromatic contrast detection thresholds as achromatic background contrast increased. A model that incorporated a normalising effect of achromatic contrast on chromatic responses, but not vice versa, best predicted our V1 data as well as behavioural thresholds. Further along the visual hierarchy, the dynamic range of chromatic responses was maintained when compared to achromatic responses, which became increasingly compressive.

Spatial correspondence of cortical activity measured with whole head fNIRS and fMRI: Toward clinical use within subject.

Functional near infrared spectroscopy (fNIRS) and functional magnetic resonance imaging (fMRI) both measure the hemodynamic response, and so both imaging modalities are expected to have a strong correspondence in regions of cortex adjacent to the scalp. To assess whether fNIRS can be used clinically in a manner similar to fMRI, 22 healthy adult participants underwent same-day fMRI and whole-head fNIRS testing while they performed separate motor (finger tapping) and visual (flashing checkerboard) tasks. Analyses were conducted within and across subjects for each imaging approach, and regions of significant task-related activity were compared on the cortical surface. The spatial correspondence between fNIRS and fMRI detection of task-related activity was good in terms of true positive rate, with fNIRS overlap of up to 68 % of the fMRI for analyses across subjects (group analysis) and an average overlap of up to 47.25 % for individual analyses within subject. At the group level, the positive predictive value of fNIRS was 51 % relative to fMRI. The positive predictive value for within subject analyses was lower (41.5 %), reflecting the presence of significant fNIRS activity in regions without significant fMRI activity. This could reflect task-correlated sources of physiologic noise and/or differences in the sensitivity of fNIRS and fMRI measures to changes in separate (vs. combined) measures of oxy and de-oxyhemoglobin. The results suggest whole-head fNIRS as a noninvasive imaging modality with promising clinical utility for the functional assessment of brain activity in superficial regions of cortex physically adjacent to the skull.

The transition from vision to language: Distinct patterns of functional connectivity for subregions of the visual word form area.

Reading entails transforming visual symbols to sound and meaning. This process depends on specialized circuitry in the visual cortex, the visual word form area (VWFA). Recent findings suggest that this text-selective cortex comprises at least two distinct subregions: the more posterior VWFA-1 is sensitive to visual features, while the more anterior VWFA-2 processes higher level language information. Here, we explore whether these two subregions also exhibit different patterns of functional connectivity. To this end, we capitalize on two complementary datasets: Using the Natural Scenes Dataset (NSD), we identify text-selective responses in high-quality 7T adult data (N = 8), and investigate functional connectivity patterns of VWFA-1 and VWFA-2 at the individual level. We then turn to the Healthy Brain Network (HBN) database to assess whether these patterns replicate in a large developmental sample (N = 224; age 6-20 years), and whether they relate to reading development. In both datasets, we find that VWFA-1 is primarily correlated with bilateral visual regions. In contrast, VWFA-2 is more strongly correlated with language regions in the frontal and lateral parietal lobes, particularly the bilateral inferior frontal gyrus. Critically, these patterns do not generalize to adjacent face-selective regions, suggesting a specific relationship between VWFA-2 and the frontal language network. No correlations were observed between functional connectivity and reading ability. Together, our findings support the distinction between subregions of the VWFA, and suggest that functional connectivity patterns in the ventral temporal cortex are consistent over a wide range of reading skills.

Developmentally stable representations of naturalistic image structure in macaque visual cortex.

We studied visual development in macaque monkeys using texture stimuli, matched in local spectral content but varying in "naturalistic" structure. In adult monkeys, naturalistic textures preferentially drive neurons in areas V2 and V4, but not V1. We paired behavioral measurements of naturalness sensitivity with separately-obtained neuronal population recordings from neurons in areas V1, V2, V4, and inferotemporal cortex (IT). We made behavioral measurements from 16 weeks of age and physiological measurements as early as 20 weeks, and continued through 56 weeks. Behavioral sensitivity reached half of maximum at roughly 25 weeks of age. Neural sensitivities remained stable from the earliest ages tested. As in adults, neural sensitivity to naturalistic structure increased from V1 to V2 to V4. While sensitivities in V2 and IT were similar, the dimensionality of the IT representation was more similar to V4's than to V2's.

Behavioral strategy shapes activation of the Vip-Sst disinhibitory circuit in visual cortex.

In complex environments, animals can adopt diverse strategies to find rewards. How distinct strategies differentially engage brain circuits is not well understood. Here, we investigate this question, focusing on the cortical Vip-Sst disinhibitory circuit between vasoactive intestinal peptide-postive (Vip) interneurons and somatostatin-positive (Sst) interneurons. We characterize the behavioral strategies used by mice during a visual change detection task. Using a dynamic logistic regression model, we find that individual mice use mixtures of a visual comparison strategy and a statistical timing strategy. Separately, mice also have periods of task engagement and disengagement. Two-photon calcium imaging shows large strategy-dependent differences in neural activity in excitatory, Sst inhibitory, and Vip inhibitory cells in response to both image changes and image omissions. In contrast, task engagement has limited effects on neural population activity. We find that the diversity of neural correlates of strategy can be understood parsimoniously as the increased activation of the Vip-Sst disinhibitory circuit during the visual comparison strategy, which facilitates task-appropriate responses.