Human subcortical pathways automatically detect collision trajectory without attention and awareness.

Detecting imminent collisions is essential for survival. Here, we used high-resolution fMRI at 7 Tesla to investigate the role of attention and consciousness for detecting collision trajectory in human subcortical pathways. Healthy participants can precisely discriminate collision from near-miss trajectory of an approaching object, with pupil size change reflecting collision sensitivity. Subcortical pathways from the superior colliculus (SC) to the ventromedial pulvinar (vmPul) and ventral tegmental area (VTA) exhibited collision-sensitive responses even when participants were not paying attention to the looming stimuli. For hemianopic patients with unilateral lesions of the geniculostriate pathway, the ipsilesional SC and VTA showed significant activation to collision stimuli in their scotoma. Furthermore, stronger SC responses predicted better behavioral performance in collision detection even in the absence of awareness. Therefore, human tectofugal pathways could automatically detect collision trajectories without the observers' attention to and awareness of looming stimuli, supporting "blindsight" detection of impending visual threats.

Attentional selection and communication through coherence: Scope and limitations.

Synchronous neural oscillations are strongly associated with a variety of perceptual, cognitive, and behavioural processes. It has been proposed that the role of the synchronous oscillations in these processes is to facilitate information transmission between brain areas, the 'communication through coherence,' or CTC hypothesis. The details of how this mechanism would work, however, and its causal status, are still unclear. Here we investigate computationally a proposed mechanism for selective attention that directly implicates the CTC as causal. The mechanism involves alpha band (about 10 Hz) oscillations, originating in the pulvinar nucleus of the thalamus, being sent to communicating cortical areas, organizing gamma (about 40 Hz) oscillations there, and thus facilitating phase coherence and communication between them. This is proposed to happen contingent on control signals sent from higher-level cortical areas to the thalamic reticular nucleus, which controls the alpha oscillations sent to cortex by the pulvinar. We studied the scope of this mechanism in parameter space, and limitations implied by this scope, using a computational implementation of our conceptual model. Our results indicate that, although the CTC-based mechanism can account for some effects of top-down and bottom-up attentional selection, its limitations indicate that an alternative mechanism, in which oscillatory coherence is caused by communication between brain areas rather than being a causal factor for it, might operate in addition to, or even instead of, the CTC mechanism.

Multimodal study of multilevel pulvino-temporal connections: a new piece in the puzzle of lexical retrieval networks.

Advanced methods of imaging and mapping the healthy and lesioned brain have allowed for the identification of the cortical nodes and white matter tracts supporting the dual neurofunctional organization of language networks in a dorsal phonological and a ventral semantic stream. Much less understood are the anatomical correlates of the interaction between the two streams; one hypothesis being that of a subcortically mediated interaction, through crossed cortico-striato-thalamo-cortical and cortico-thalamo-cortical loops. In this regard, the pulvinar is the thalamic subdivision that has most regularly appeared as implicated in the processing of lexical retrieval. However, descriptions of its connections with temporal (language) areas remain scarce. Here we assess this pulvino-temporal connectivity using a combination of state-of-the-art techniques: white matter stimulation in awake surgery and postoperative diffusion MRI (n = 4), virtual dissection from the Human Connectome Project 3 and 7 T datasets (n = 172) and operative microscope-assisted post-mortem fibre dissection (n = 12). We demonstrate the presence of four fundamental fibre contingents: (i) the anterior component (Arnold's bundle proper) initially described by Arnold in the 19th century and destined to the anterior temporal lobe; (ii) the optic radiations-like component, which leaves the pulvinar accompanying the optical radiations and reaches the posterior basal temporal cortices; (iii) the lateral component, which crosses the temporal stem orthogonally and reaches the middle temporal gyrus; and (iv) the auditory radiations-like component, which leaves the pulvinar accompanying the auditory radiations to the superomedial aspect of the temporal operculum, just posteriorly to Heschl's gyrus. Each of those components might correspond to a different level of information processing involved in the lexical retrieval process of picture naming.

Pulvinar Response Profiles and Connectivity Patterns to Object Domains.

Distributed cortical regions show differential responses to visual objects belonging to different domains varying by animacy (e.g., animals vs tools), yet it remains unclear whether this is an organization principle also applying to the subcortical structures. Combining multiple fMRI activation experiments (two main experiments and six validation datasets; 12 females and 9 males in the main Experiment 1; 10 females and 10 males in the main Experiment 2), resting-state functional connectivity, and task-based dynamic causal modeling analysis in human subjects, we found that visual processing of images of animals and tools elicited different patterns of response in the pulvinar, with robust left lateralization for tools, and distinct, bilateral (with rightward tendency) clusters for animals. Such domain-preferring activity distribution in the pulvinar was associated with the magnitude with which the voxels were intrinsically connected with the corresponding domain-preferring regions in the cortex. The pulvinar-to-right-amygdala path showed a one-way shortcut supporting the perception of animals, and the modulation connection from pulvinar to parietal showed an advantage to the perception of tools. These results incorporate the subcortical regions into the object processing network and highlight that domain organization appears to be an overarching principle across various processing stages in the brain.SIGNIFICANCE STATEMENT Viewing objects belonging to different domains elicited different cortical regions, but whether the domain organization applied to the subcortical structures (e.g., pulvinar) was unknown. Multiple fMRI activation experiments revealed that object pictures belonging to different domains elicited differential patterns of response in the pulvinar, with robust left lateralization for tool pictures, and distinct, bilateral (with rightward tendency) clusters for animals. Combining the resting-state functional connectivity and dynamic causal modeling analysis on task-based fMRI data, we found domain-preferring activity distribution in the pulvinar aligned with that in cortical regions. These results highlight the need for coherent visual theories that explain the mechanisms underlying the domain organization across various processing stages.

Functional connectivity between medial pulvinar and cortical networks as a predictor of arousal to noxious stimuli during sleep.

The interruption of sleep by a nociceptive stimulus is favoured by an increase in the pre-stimulus functional connectivity between sensory and higher level cortical areas. In addition, stimuli inducing arousal also trigger a widespread electroencephalographic (EEG) response reflecting the coordinated activation of a large cortical network. Because functional connectivity between distant cortical areas is thought to be underpinned by trans-thalamic connections involving associative thalamic nuclei, we investigated the possible involvement of one principal associative thalamic nucleus, the medial pulvinar (PuM), in the sleeper's responsiveness to nociceptive stimuli. Intra-cortical and intra-thalamic signals were analysed in 440 intracranial electroencephalographic (iEEG) segments during nocturnal sleep in eight epileptic patients receiving laser nociceptive stimuli. The spectral coherence between the PuM and 10 cortical regions grouped in networks was computed during 5 s before and 1 s after the nociceptive stimulus and contrasted according to the presence or absence of an arousal EEG response. Pre- and post-stimulus phase coherence between the PuM and all cortical networks was significantly increased in instances of arousal, both during N2 and paradoxical (rapid eye movement [REM]) sleep. Thalamo-cortical enhancement in coherence involved both sensory and higher level cortical networks and predominated in the pre-stimulus period. The association between pre-stimulus widespread increase in thalamo-cortical coherence and subsequent arousal suggests that the probability of sleep interruption by a noxious stimulus increases when it occurs during phases of enhanced trans-thalamic transfer of information between cortical areas.

Macaque claustrum, pulvinar and putative dorsolateral amygdala support the cross-modal association of social audio-visual stimuli based on meaning.

Social communication draws on several cognitive functions such as perception, emotion recognition and attention. The association of audio-visual information is essential to the processing of species-specific communication signals. In this study, we use functional magnetic resonance imaging in order to identify the subcortical areas involved in the cross-modal association of visual and auditory information based on their common social meaning. We identified three subcortical regions involved in audio-visual processing of species-specific communicative signals: the dorsolateral amygdala, the claustrum and the pulvinar. These regions responded to visual, auditory congruent and audio-visual stimulations. However, none of them was significantly activated when the auditory stimuli were semantically incongruent with the visual context, thus showing an influence of visual context on auditory processing. For example, positive vocalization (coos) activated the three subcortical regions when presented in the context of positive facial expression (lipsmacks) but not when presented in the context of negative facial expression (aggressive faces). In addition, the medial pulvinar and the amygdala presented multisensory integration such that audiovisual stimuli resulted in activations that were significantly higher than those observed for the highest unimodal response. Last, the pulvinar responded in a task-dependent manner, along a specific spatial sensory gradient. We propose that the dorsolateral amygdala, the claustrum and the pulvinar belong to a multisensory network that modulates the perception of visual socioemotional information and vocalizations as a function of the relevance of the stimuli in the social context. SIGNIFICANCE STATEMENT: Understanding and correctly associating socioemotional information across sensory modalities, such that happy faces predict laughter and escape scenes predict screams, is essential when living in complex social groups. With the use of functional magnetic imaging in the awake macaque, we identify three subcortical structures-dorsolateral amygdala, claustrum and pulvinar-that only respond to auditory information that matches the ongoing visual socioemotional context, such as hearing positively valenced coo calls and seeing positively valenced mutual grooming monkeys. We additionally describe task-dependent activations in the pulvinar, organizing along a specific spatial sensory gradient, supporting its role as a network regulator.

Pulvinar slits: Cellulose-deficient and de-methyl-esterified pectin-rich structures in a legume motor cell.

The cortical motor cells (CMCs) in a legume pulvinus execute the reversible deformation in leaf movement that is driven by changes in turgor pressure. In contrast to the underlying osmotic regulation property, the cell wall structure of CMCs that contributes to the movement has yet to be characterized in detail. Here, we report that the cell wall of CMCs has circumferential slits with low levels of cellulose deposition, which are widely conserved among legume species. This structure is unique and distinct from that of any other primary cell walls reported so far; thus, we named them "pulvinar slits." Notably, we predominantly detected de-methyl-esterified homogalacturonan inside pulvinar slits, with a low deposition of highly methyl-esterified homogalacturonan, as with cellulose. In addition, Fourier transform infrared spectroscopy analysis indicated that the cell wall composition of pulvini is different from that of other axial organs, such as petioles or stems. Moreover, monosaccharide analysis showed that pulvini are pectin-rich organs like developing stems and that the amount of galacturonic acid in pulvini is greater than in developing stems. Computer modeling suggested that pulvinar slits facilitate anisotropic extension in the direction perpendicular to the slits in the presence of turgor pressure. When tissue slices of CMCs were transferred to different extracellular osmotic conditions, pulvinar slits altered their opening width, indicating their deformability. In this study, we thus characterized a distinctive cell wall structure of CMCs, adding to our knowledge of repetitive and reversible organ deformation as well as the structural diversity and function of the plant cell wall.

Thalamic stereoelectroencephalography for neuromodulation target selection: Proof of concept and review of literature of pulvinar direct electrical stimulation.

In patients with drug-resistant epilepsy (DRE) who are not candidates for resective surgery, various thalamic nuclei, including the anterior, centromedian, and pulvinar nuclei, have been extensively investigated as targets for neuromodulation. However, the therapeutic effects of different targets for thalamic neuromodulation on various types of epilepsy are not well understood. Here, we present a 32-year-old patient with multifocal bilateral temporoparieto-occipital epilepsy and bilateral malformations of cortical development (MCDs) who underwent bilateral stereoelectroencephalographic (SEEG) recordings of the aforementioned three thalamic nuclei bilaterally. The change in the rate of interictal epileptiform discharges (IEDs) from baseline were compared in temporal, central, parietal, and occipital regions after direct electrical stimulation (DES) of each thalamic nucleus. A significant decrease in the rate of IEDs (33% from baseline) in the posterior quadrant regions was noted in the ipsilateral as well as contralateral hemisphere following DES of the pulvinar. A scoping review was also performed to better understand the current standpoint of pulvinar thalamic stimulation in the treatment of DRE. The therapeutic effect of neuromodulation can differ among thalamic nuclei targets and epileptogenic zones (EZs). In patients with multifocal EZs with extensive MCDs, personalized thalamic targeting could be achieved through DES with thalamic SEEG electrodes.

Distinct neural signatures of pulvinar in C9orf72 amyotrophic lateral sclerosis mutation carriers and noncarriers.

BACKGROUND AND PURPOSE: Thalamic alterations have been reported as a major feature in presymptomatic and symptomatic patients carrying the C9orf72 mutation across the frontotemporal dementia-amyotrophic lateral sclerosis (ALS) spectrum. Specifically, the pulvinar, a high-order thalamic nucleus and timekeeper for large-scale cortical networks, has been hypothesized to be involved in C9orf72-related neurodegenerative diseases. We investigated whether pulvinar volume can be useful for differential diagnosis in ALS C9orf72 mutation carriers and noncarriers and how underlying functional connectivity changes affect this region. METHODS: We studied 19 ALS C9orf72 mutation carriers (ALSC9+) accurately matched with wild-type ALS (ALSC9-) and ALS mimic (ALSmimic) patients using structural and resting-state functional magnetic resonance imaging data. Pulvinar volume was computed using automatic segmentation. Seed-to-voxel functional connectivity analyses were performed using seeds from a pulvinar functional parcellation. RESULTS: Pulvinar structural integrity had high discriminative values for ALSC9+ patients compared to ALSmimic (area under the curve [AUC] = 0.86) and ALSC9- (AUC = 0.77) patients, yielding a volume cutpoint of approximately 0.23%. Compared to ALSmimic, ALSC9- showed increased anterior, inferior, and lateral pulvinar connections with bilateral occipital-temporal-parietal regions, whereas ALSC9+ showed no differences. ALSC9+ patients when compared to ALSC9- patients showed reduced pulvinar-occipital connectivity for anterior and inferior pulvinar seeds. CONCLUSIONS: Pulvinar volume could be a differential biomarker closely related to the C9orf72 mutation. A pulvinar-cortical circuit dysfunction might play a critical role in disease progression and development, in both the genetic phenotype and ALS wild-type patients.

Visual, delay, and oculomotor timing and tuning in macaque dorsal pulvinar during instructed and free choice memory saccades.

Causal perturbations suggest that primate dorsal pulvinar plays a crucial role in target selection and saccade planning, though its basic neuronal properties remain unclear. Some functional aspects of dorsal pulvinar and interconnected frontoparietal areas-e.g. ipsilesional choice bias after inactivation-are similar. But it is unknown if dorsal pulvinar shares oculomotor properties of cortical circuitry, in particular delay and choice-related activity. We investigated such properties in macaque dorsal pulvinar during instructed and free-choice memory saccades. Most recorded units showed visual (12%), saccade-related (30%), or both types of responses (22%). Visual responses were primarily contralateral; diverse saccade-related responses were predominantly post-saccadic with a weak contralateral bias. Memory delay and pre-saccadic enhancement was infrequent (11-9%)-instead, activity was often suppressed during saccade planning (25%) and further during execution (15%). Surprisingly, only few units exhibited classical visuomotor patterns combining cue and continuous delay activity or pre-saccadic ramping; moreover, most spatially-selective neurons did not encode the upcoming decision during free-choice delay. Thus, in absence of a visible goal, the dorsal pulvinar has a limited role in prospective saccade planning, with patterns partially complementing its frontoparietal partners. Conversely, prevalent visual and post-saccadic responses imply its participation in integrating spatial goals with processing across saccades.

Rapid processing of threatening faces in the amygdala of nonhuman primates: subcortical inputs and dual roles.

A subcortical pathway through the superior colliculus and pulvinar has been proposed to provide the amygdala with rapid but coarse visual information about emotional faces. However, evidence for short-latency, facial expression-discriminating responses from individual amygdala neurons is lacking; even if such a response exists, how it might contribute to stimulus detection is unclear. Also, no definitive anatomical evidence is available for the assumed pathway. Here we showed that ensemble responses of amygdala neurons in monkeys carried robust information about open-mouthed, presumably threatening, faces within 50 ms after stimulus onset. This short-latency signal was not found in the visual cortex, suggesting a subcortical origin. Temporal analysis revealed that the early response contained excitatory and suppressive components. The excitatory component may be useful for sending rapid signals downstream, while the sharpening of the rising phase of later-arriving inputs (presumably from the cortex) by the suppressive component might improve the processing of facial expressions over time. Injection of a retrograde trans-synaptic tracer into the amygdala revealed presumed monosynaptic labeling in the pulvinar and disynaptic labeling in the superior colliculus, including the retinorecipient layers. We suggest that the early amygdala responses originating from the colliculo-pulvino-amygdalar pathway play dual roles in threat detection.

Multisensory integration in neurons of the medial pulvinar of macaque monkey.

The pulvinar is a heterogeneous thalamic nucleus, which is well developed in primates. One of its subdivisions, the medial pulvinar, is connected to many cortical areas, including the visual, auditory, and somatosensory cortices, as well as with multisensory areas and premotor areas. However, except for the visual modality, little is known about its sensory functions. A hypothesis is that, as a region of convergence of information from different sensory modalities, the medial pulvinar plays a role in multisensory integration. To test this hypothesis, 2 macaque monkeys were trained to a fixation task and the responses of single-units to visual, auditory, and auditory-visual stimuli were examined. Analysis revealed auditory, visual, and multisensory neurons in the medial pulvinar. It also revealed multisensory integration in this structure, mainly suppressive (the audiovisual response is less than the strongest unisensory response) and subadditive (the audiovisual response is less than the sum of the auditory and the visual responses). These findings suggest that the medial pulvinar is involved in multisensory integration.

Context-dependent attentional spotlight in pulvinar-V1 interaction.

Spatial attention is often described as a mental spotlight that enhances information processing at the attended location. Using fMRI, we investigated background connectivity between the pulvinar and V1 in relation to focused versus diffused attention allocation, in weak and strong crowding contexts. Our findings revealed that focused attention led to enhanced correlations between the pulvinar and V1. Notably, this modulation was initiated by the pulvinar, and the strength of the modulation was dependent on the saliency of the target. These findings suggest that the pulvinar initiates information reweighting to V1, which underlies attentional selection in cluttered scenes.

Modulation of pulvinar connectivity with cortical areas in the control of selective visual attention.

Selective attention mechanisms operate across large-scale cortical networks by amplifying behaviorally relevant sensory information while suppressing interference from distractors. Although it is known that fronto-parietal regions convey information about attentional priorities, it is unclear how such cortical communication is orchestrated. Based on its unique connectivity pattern with the cortex, we hypothesized that the pulvinar, a nucleus of the thalamus, may play a key role in coordinating and modulating remote cortical activity during selective attention. By using a visual task that orthogonally manipulated top-down selection and bottom-up competition during functional MRI, we investigated the modulations induced by task-relevant (spatial cue) and task-irrelevant but salient (distractor) stimuli on functional interactions between the pulvinar, occipito-temporal cortex, and frontoparietal areas involved in selective attention. Pulvinar activity and connectivity were distinctively modulated during the co-occurrence of the cue and salient distractor stimuli, as opposed to the presence of one of these factors alone. Causal modelling analysis further indicated that the pulvinar acted by weighting excitatory signals to cortical areas, predominantly in the presence of both the cue and the distractor. These results converge to support a pivotal role of the pulvinar in integrating top-down and bottom-up signals among distributed networks when confronted with conflicting visual stimuli, and thus contributing to shape priority maps for the guidance of attention.

LSD-induced changes in the functional connectivity of distinct thalamic nuclei.

The role of the thalamus in mediating the effects of lysergic acid diethylamide (LSD) was recently proposed in a model of communication and corroborated by imaging studies. However, a detailed analysis of LSD effects on nuclei-resolved thalamocortical connectivity is still missing. Here, in a group of healthy volunteers, we evaluated whether LSD intake alters the thalamocortical coupling in a nucleus-specific manner. Structural and resting-state functional Magnetic Resonance Imaging (MRI) data were acquired in a placebo-controlled study on subjects exposed to acute LSD administration. Structural MRI was used to parcel the thalamus into its constituent nuclei based on individual anatomy. Nucleus-specific changes of resting-state functional MRI (rs-fMRI) connectivity were mapped using a seed-based approach. LSD intake selectively increased the thalamocortical functional connectivity (FC) of the ventral complex, pulvinar, and non-specific nuclei. Functional coupling was increased between these nuclei and sensory cortices that include the somatosensory and auditory networks. The ventral and pulvinar nuclei also exhibited increased FC with parts of the associative cortex that are dense in serotonin type 2A receptors. These areas are hyperactive and hyper-connected upon LSD intake. At subcortical levels, LSD increased the functional coupling among the thalamus's ventral, pulvinar, and non-specific nuclei, but decreased the striatal-thalamic connectivity. These findings unravel some LSD effects on the modulation of subcortical-cortical circuits and associated behavioral outputs.

Network Localization of Unconscious Visual Perception in Blindsight.

OBJECTIVE: Blindsight is a disorder where brain injury causes loss of conscious but not unconscious visual perception. Prior studies have produced conflicting results regarding the neuroanatomical pathways involved in this unconscious perception. METHODS: We performed a systematic literature search to identify lesion locations causing visual field loss in patients with blindsight (n = 34) and patients without blindsight (n = 35). Resting state functional connectivity between each lesion location and all other brain voxels was computed using a large connectome database (n = 1,000). Connections significantly associated with blindsight (vs no blindsight) were identified. RESULTS: Functional connectivity between lesion locations and the ipsilesional medial pulvinar was significantly associated with blindsight (family wise error p = 0.029). No significant connectivity differences were found to other brain regions previously implicated in blindsight. This finding was independent of methods (eg, flipping lesions to the left or right) and stimulus type (moving vs static). INTERPRETATION: Connectivity to the ipsilesional medial pulvinar best differentiates lesion locations associated with blindsight versus those without blindsight. Our results align with recent data from animal models and provide insight into the neuroanatomical substrate of unconscious visual abilities in patients. ANN NEUROL 2022;91:217-224.

Context-dependent and dynamic functional influence of corticothalamic pathways to first- and higher-order visual thalamus.

Layer 6 (L6) is the sole purveyor of corticothalamic (CT) feedback to first-order thalamus and also sends projections to higher-order thalamus, yet how it engages the full corticothalamic circuit to contribute to sensory processing in an awake animal remains unknown. We sought to elucidate the functional impact of L6CT projections from the primary visual cortex to the dorsolateral geniculate nucleus (first-order) and pulvinar (higher-order) using optogenetics and extracellular electrophysiology in awake mice. While sustained L6CT photostimulation suppresses activity in both visual thalamic nuclei in vivo, moderate-frequency (10 Hz) stimulation powerfully facilitates thalamic spiking. We show that each stimulation paradigm differentially influences the balance between monosynaptic excitatory and disynaptic inhibitory corticothalamic pathways to the dorsolateral geniculate nucleus and pulvinar, as well as the prevalence of burst versus tonic firing. Altogether, our results support a model in which L6CTs modulate first- and higher-order thalamus through parallel excitatory and inhibitory pathways that are highly dynamic and context-dependent.

A structural and resting-state functional connectivity investigation of the pulvinar in elderly individuals and Alzheimer's disease patients.

In Alzheimer's disease (AD), structural and functional changes in the brain may give rise to disruption of specific cognitive functions. The aim of this study is to investigate the functional connectivity alterations in the pulvinar's subdivisions and total pulvinar voxel-based morphometry (VBM) changes in individuals with AD and healthy controls. A seed-based functional connectivity analysis was applied to the anterior, inferior, lateral, and medial pulvinar in each hemisphere. Furthermore, VBM analysis was carried out to compare gray matter (GM) volume differences in the pulvinar and thalamus between the two groups. Connectivity analysis revealed that the pulvinar subdivisions had decreased connectivity in individuals with AD. In addition, the pulvinar and thalamus in each hemisphere were significantly smaller in the AD group. The pulvinar may have a role in AD-related cognitive impairments and the intrinsic connectivity network changes and GM loss in pulvinar subdivisions suggest the cognitive deterioration occurring in those with AD. HIGHLIGHTS: The pulvinar may play a role in pathophysiology of cognitive impairments in those with Alzheimer's disease (AD). Decreased structural volume and functional connectivity were found in patients with AD. The inferior pulvinar is functionally the most affected subdivision by AD compared to the others.

Contribution of the Pulvinar and Lateral Geniculate Nucleus to the Control of Visually Guided Saccades in Blindsight Monkeys.

After damage to the primary visual cortex (V1), conscious vision is impaired. However, some patients can respond to visual stimuli presented in their lesion-affected visual field using residual visual pathways bypassing V1. This phenomenon is called "blindsight." Many studies have tried to identify the brain regions responsible for blindsight, and the pulvinar and/or lateral geniculate nucleus (LGN) are suggested to play key roles as the thalamic relay of visual signals. However, there are critical problems regarding these preceding studies in that subjects with different sized lesions and periods of time after lesioning were investigated; furthermore, the ability of blindsight was assessed with different measures. In this study, we used double dissociation to clarify the roles of the pulvinar and LGN by pharmacological inactivation of each region and investigated the effects in a simple task with visually guided saccades (VGSs) using monkeys with a unilateral V1 lesion, by which nearly all of the contralesional visual field was affected. Inactivating either the ipsilesional pulvinar or LGN impaired VGS toward a visual stimulus in the affected field. In contrast, inactivation of the contralesional pulvinar had no clear effect, but inactivation of the contralesional LGN impaired VGS to the intact visual field. These results suggest that the pulvinar and LGN play key roles in performing the simple VGS task after V1 lesioning, and that the visuomotor functions of blindsight monkeys were supported by plastic changes in the visual pathway involving the pulvinar, which emerged after V1 lesioning.SIGNIFICANCE STATEMENT Many studies have been devoted to understanding the mechanism of mysterious symptom called "blindsight," in which patients with damage to the primary visual cortex (V1) can respond to visual stimuli despite loss of visual awareness. However, there is still a debate on the thalamic relay of visual signals. In this study, to pin down the issue, we tried double dissociation in the same subjects (hemi-blindsight macaque monkeys) and clarified that the lateral geniculate nucleus (LGN) plays a major role in simple visually guided saccades in the intact state, while both pulvinar and LGN critically contribute after the V1 lesioning, suggesting that plasticity in the visual pathway involving the pulvinar underlies the blindsight.

Transient Subplate Sublayer Forms Unique Corridor for Differential Ingrowth of Associative Pulvinar and Primary Visual Projection in the Prospective Visual Cortical Areas of the Human Fetal Occipital Lobe.

Cytoarchitectonical parcellation of the visual cortex into the striate and extrastriate cortex requires complex histogenetic events within a precise spatio-temporal frame to attain the specification of areal domains and associated thalamocortical connections during the fetal brain development. We analyzed a deep subplate cellular monolayer (subplate "corridor" cells) present during a restricted period of 13-15 postconceptional weeks, showing the 3D caudo-ventro-medial position in the human fetal occipital lobe, corresponding to the segregation point of pulvinocortical and geniculocortical fibers at the prospective area 17/18 border. Immunofluorescence stainings revealed subplate "corridor" cells as the specific class of the deepest subplate neurons (NeuN+, Tbr1+, Cplx3+) expressing axon guidance molecules (Sema-3A+, EphA6+), presumably for the attraction of pulvinocortical axons and the repulsion of geniculocortical axons growing at that time (SNAP25+, Syn+, FN+). Furthermore, quantitative analysis of the subplate "corridor" region of interest, considering cell number, immunofluorescence signal intensity per cell and per region, revealed significant differences to other regions across the tangential circumference of the developing cerebral wall. Thus, our study sheds new light on the deepest subplate sublayer, strategically aligned along the growing axon systems in the prospective visual system, suggesting the establishment of the area 17/18 border by differential thalamocortical input during the fetal brain development.