Activity In Lateral Geniculate Nucleus Research Articles

Functional localization of the human auditory and visual thalamus using a thalamic localizer functional magnetic resonance imaging task

Abstract Functional magnetic resonance imaging (fMRI) of the auditory and visual sensory systems of the human brain is an active area of investigation in the study of human health and disease. The medial geniculate nucleus (MGN) and lateral geniculate nucleus (LGN) are key thalamic nuclei involved in the processing and relay of auditory and visual information, respectively, and are the subject of blood-oxygen-level-dependent (BOLD) fMRI studies of neural activation and functional connectivity in human participants. However, localization of BOLD fMRI signal originating from neural activity in MGN and LGN remains a technical challenge, due, in part, to the poor definition of boundaries of these thalamic nuclei in standard T1-weighted and T2-weighted magnetic resonance imaging sequences. Here, we report the development and evaluation of an auditory and visual sensory thalamic localizer (TL) fMRI task that produces participant-specific functionally-defined regions of interest (fROIs) of both MGN and LGN, using 3 Tesla multiband fMRI and a clustered-sparse temporal acquisition sequence, in less than 16 minutes of scan time. We demonstrate the use of MGN and LGN fROIs obtained from the TL fMRI task in standard resting-state functional connectivity (RSFC) fMRI analyses in the same participants. In RSFC analyses, we validated the specificity of MGN and LGN fROIs for signals obtained from primary auditory and visual cortex, respectively, and benchmarked their performance against alternative atlas- and segmentation-based localization methods. The TL fMRI task and analysis code (written in Presentation and MATLAB, respectively) have been made freely available to the wider research community.

Optogenetic activation of visual thalamus generates artificial visual percepts.

The lateral geniculate nucleus (LGN), a retinotopic relay center where visual inputs from the retina are processed and relayed to the visual cortex, has been proposed as a potential target for artificial vision. At present, it is unknown whether optogenetic LGN stimulation is sufficient to elicit behaviorally relevant percepts, and the properties of LGN neural responses relevant for artificial vision have not been thoroughly characterized. Here, we demonstrate that tree shrews pretrained on a visual detection task can detect optogenetic LGN activation using an AAV2-CamKIIα-ChR2 construct and readily generalize from visual to optogenetic detection. Simultaneous recordings of LGN spiking activity and primary visual cortex (V1) local field potentials (LFP) during optogenetic LGN stimulation show that LGN neurons reliably follow optogenetic stimulation at frequencies up to 60 Hz, and uncovered a striking phase locking between the V1 local field potential (LFP) and the evoked spiking activity in LGN. These phase relationships were maintained over a broad range of LGN stimulation frequencies, up to 80 Hz, with spike field coherence values favoring higher frequencies, indicating the ability to relay temporally precise information to V1 using light activation of the LGN. Finally, V1 LFP responses showed sensitivity values to LGN optogenetic activation that were similar to the animal's behavioral performance. Taken together, our findings confirm the LGN as a potential target for visual prosthetics in a highly visual mammal closely related to primates.

Mnemonic representations in human lateral geniculate nucleus.

There is a growing appreciation for the role of the thalamus in high-level cognition. Motivated by findings that internal cognitive state drives activity in feedback layers of primary visual cortex (V1) that target the lateral geniculate nucleus (LGN), we investigated the role of LGN in working memory (WM). Specifically, we leveraged model-based neuroimaging approaches to test the hypothesis that human LGN encodes information about spatial locations temporarily encoded in WM. First, we localized and derived a detailed topographic organization in LGN that accords well with previous findings in humans and non-human primates. Next, we used models constructed on the spatial preferences of LGN populations in order to reconstruct spatial locations stored in WM as subjects performed modified memory-guided saccade tasks. We found that population LGN activity faithfully encoded the spatial locations held in memory in all subjects. Importantly, our tasks and models allowed us to dissociate the locations of retinal stimulation and the motor metrics of memory-guided saccades from the maintained spatial locations, thus confirming that human LGN represents true WM information. These findings add LGN to the growing list of subcortical regions involved in WM, and suggest a key pathway by which memories may influence incoming processing at the earliest levels of the visual hierarchy.

Neural Dynamics during Binocular Rivalry: Indications from Human Lateral Geniculate Nucleus.

When two sufficiently different stimuli are presented to each eye, perception alternates between them. This binocular rivalry is conceived as a competition for representation in the single stream of visual consciousness. The magnocellular (M) and parvocellular (P) pathways, originating in the retina, encode disparate information, but their potentially different contributions to binocular rivalry have not been determined. Here, we used functional magnetic resonance imaging to measure the human lateral geniculate nucleus (LGN), where the M and P neurons are segregated into layers receiving input from a single eye. We had three participants (one male, two females) and used achromatic stimuli to avoid contributions from color opponent neurons that may have confounded previous studies. We observed activity in the eye-specific regions of LGN correlated with perception, with similar magnitudes during rivalry or physical stimuli alternations, also similar in the M and P regions. These results suggest that LGN activity reflects our perceptions during binocular rivalry and is not simply an artifact of color opponency. Further, perception appears to be a global phenomenon in the LGN, not just limited to a single information channel.

Attention differentially modulates multiunit activity in the lateral geniculate nucleus and V1 of macaque monkeys.

Attention promotes the selection of behaviorally relevant sensory signals from the barrage of sensory information available. Visual attention modulates the gain of neuronal activity in all visual brain areas examined, although magnitudes of gain modulations vary across areas. For example, attention gain magnitudes in the dorsal lateral geniculate nucleus (LGN) and primary visual cortex (V1) vary tremendously across fMRI measurements in humans and electrophysiological recordings in behaving monkeys. We sought to determine whether these discrepancies are due simply to differences in species or measurement, or more nuanced properties unique to each visual brain area. We also explored whether robust and consistent attention effects, comparable to those measured in humans with fMRI, are observable in the LGN or V1 of monkeys. We measured attentional modulation of multiunit activity in the LGN and V1 of macaque monkeys engaged in a contrast change detection task requiring shifts in covert visual spatial attention. Rigorous analyses of LGN and V1 multiunit activity revealed robust and consistent attentional facilitation throughout V1, with magnitudes comparable to those observed with fMRI. Interestingly, attentional modulation in the LGN was consistently negligible. These findings demonstrate that discrepancies in attention effects are not simply due to species or measurement differences. We also examined whether attention effects correlated with the feature selectivity of recorded multiunits. Distinct relationships suggest that attentional modulation of multiunit activity depends upon the unique structure and function of visual brain areas.

Fractal spike dynamics and neuronal coupling in the primate visual system.

We measured fractal (self-similar) fluctuations in ongoing spiking activity in subcortical (lateral geniculate nucleus, LGN) and cortical (area MT) visual areas in anaesthetised marmosets. Cells in the evolutionary ancient koniocellular LGN pathway and in area MT show high-amplitude fractal fluctuations, whereas evolutionarily newer parvocellular and magnocellular LGN cells do not. Spiking activity in koniocellular cells and MT cells shows substantial correlation to the local population activity, whereas activity in parvocellular and magnocellular cells is less correlated with local activity. We develop a model consisting of a fractal process and a global rate modulation which can reproduce and explain the fundamental relationship between fractal fluctuations and population coupling in LGN and MT. The model provides a unified account of apparently disparate aspects of neural spiking activity and can improve our understanding of information processing in evolutionary ancient and modern visual pathways. The brain represents and processes information through patterns of spiking activity, which is influenced by local and widescale brain circuits as well as intrinsic neural dynamics. Whether these influences have independent or linked effects on spiking activity is, however, not known. Here we measured spiking activity in two visual centres, the lateral geniculate nucleus (LGN) and cortical area MT, in marmoset monkeys. By combining the Fano-factor time curve, power spectral analysis and rescaled range analysis, we reveal inherent fractal fluctuations of spiking activity in LGN and MT. We found that the evolutionary ancient koniocellular (K) pathway in LGN and area MT exhibits strong fractal fluctuations at short (<1s) time scales. Parvocellular (P) and magnocellular (M) LGN cells show weaker fractal fluctuations at longer (multi-second) time scales. In both LGN and MT, the amplitude and time scale of fractal fluctuations can explain short and long time scale spiking dynamics. We further show differential neuronal coupling of LGN and MT cells to local population spiking activity. The population coupling is intrinsically linked to fractal fluctuations: neurons showing stronger fluctuations are more strongly correlated to the local population activity. To understand this relationship, we modelled spiking activity using a fractal inhomogeneous Poisson process with dynamic rate, which is the product of an intrinsic stochastic fractal rate and a global modulatory gain. Our model explains the intrinsic links between neuronal spike rate and population coupling in LGN and MT, and establishes a unified account of dynamic spiking properties in afferent visual pathways.

Comparison of fMRI measurements in LGN and Primary Visual cortex with visual deficits in Glaucoma

Experimental primate glaucoma demonstrates that the retinal ganglion cell (RGC) loss is associated with atrophies in the lateral geniculate nucleus (LGN) and the primary visual cortex (V1). The purpose of our study was to determine whether, in glaucoma patients, selective behavioural deficits in the three main visual pathways (magnocellular, parvocellular, koniocellular) are associated with selective changes in the neural activity in LGN and V1. A POAG group (n=20) and a matched control group (n=20) were examined using the following tests: Visual field loss was assessed using standard automated perimetry (SAP); the Cambridge Colour Vision test (CCT) was used to assess colour deficiencies; visual thresholds along the three cardinal directions of colour space were measured (achromatic; red-greenish; lime-violet). For a subset of the participants (n=9 in either groups), functional Magnetic Resonance Imaging (fMRI) was used to obtain BOLD signals in the LGN and V1 in response to supra-threshold modulations along these three cardinal directions. We report the following results: (1) There are significant visual threshold differences between patients with Glaucoma and controls, in particular along the yellowish-violet (YV) cardinal direction. (2) The average BOLD signal in primary visual cortex (V1) is lower in the Glaucoma group compared to the control group. High thresholds along the yellowish-violet colour direction are associated with low V1 activity. (3) In contrast, the BOLD signal in the LGN is higher in Glaucoma patients compared to the controls. Within the Glaucoma group, more severe visual field defects are associated with higher LGN activity. In conclusion and contrary to our expectations, the LGN signal is increased in glaucoma patients compared to the controls. We speculate that this may reflect feedback from primary visual cortex.

Distinct patterns of corticogeniculate feedback to different layers of the lateral geniculate nucleus.

In primates, feedforward visual pathways from retina to lateral geniculate nucleus (LGN) are segregated to different layers. These layers also receive strong reciprocal feedback pathways from cortex. The degree to which feedforward streams in primates are segregated from feedback streams remains unclear. Here, we asked whether corticogeniculate cells that innervate the magnocellular (M), parvocellular (P), and koniocellular (K) layers of the LGN in the prosimian primate bush baby (Otolemur garnettii) can be distinguished based on either the laminar distribution or morphological characteristics of their axons and synaptic contacts in LGN, or on their cell body position, size, and dendritic distribution in cortex. Corticogeniculate axons and synapses were labeled anterogradely with biotinylated dextran injections in layer 6 of cortex. Corticogeniculate cell bodies were first labeled with fluorescent dextran injections limited to individual M, P, or K LGN layers and then filled with biotinylated Lucifer yellow. Results showed that feedback to the M or P LGN layers arises from cells with dendrites primarily confined to cortical layer 6 and axons restricted to either M or P LGN layers, but not both. Feedback to K LGN layers arises from cells: 1) whose dendrites distribute rather evenly across cortical layers 5 and 6; 2) whose dendrites always extend into layer 4; and 3) whose axons are never confined to K layers but always overlap with either P or M layers. Corticogeniculate axons also showed distributions that were retinotopically precise based on known receptive field sizes of layer 6 cells, and these axons mainly made synapses with glutamatergic projection neurons in the LGN in all layers. Taken together with prior physiological results, we argue that the morphological differences between the three corticogeniculate pathways show that the M and P feedback pathways could rapidly and specifically enhance local LGN activity, while we speculate that the K feedback pathway is organized to temporally synchronize activity between LGN and cortex.

Simultaneous recordings from the primary visual cortex and lateral geniculate nucleus reveal rhythmic interactions and a cortical source for γ-band oscillations.

Oscillatory synchronization of neuronal activity has been proposed as a mechanism to modulate effective connectivity between interacting neuronal populations. In the visual system, oscillations in the gamma-frequency range (30-100 Hz) are thought to subserve corticocortical communication. To test whether a similar mechanism might influence subcortical-cortical communication, we recorded local field potential activity from retinotopically aligned regions in the lateral geniculate nucleus (LGN) and primary visual cortex (V1) of alert macaque monkeys viewing stimuli known to produce strong cortical gamma-band oscillations. As predicted, we found robust gamma-band power in V1. In contrast, visual stimulation did not evoke gamma-band activity in the LGN. Interestingly, an analysis of oscillatory phase synchronization of LGN and V1 activity identified synchronization in the alpha (8-14 Hz) and beta (15-30 Hz) frequency bands. Further analysis of directed connectivity revealed that alpha-band interactions mediated corticogeniculate feedback processing, whereas beta-band interactions mediated geniculocortical feedforward processing. These results demonstrate that although the LGN and V1 display functional interactions in the lower frequency bands, gamma-band activity in the alert monkey is largely an emergent property of cortex.

Feedforward Origins of Response Variability Underlying Contrast Invariant Orientation Tuning in Cat Visual Cortex

Contrast invariant orientation tuning in simple cells of the visual cortex depends critically on contrast dependent trial-to-trial variability in their membrane potential responses. This observation raises the question of whether this variability originates from within the cortical circuit or the feedforward inputs from the lateral geniculate nucleus (LGN). To distinguish between these two sources of variability, we first measured membrane potential responses while inactivating the surrounding cortex, and found that response variability was nearly unaffected. We then studied variability in the LGN, including contrast dependence, and the trial-to-trial correlation in responses between nearby neurons. Variability decreased significantly with contrast, whereas correlation changed little. When these experimentally measured parameters of variability were applied to a feedforward model of simple cells that included realistic mechanisms of synaptic integration, contrast-dependent, orientation independent variability emerged in the membrane potential responses. Analogous mechanisms might contribute to the stimulus dependence and propagation of variability throughout the neocortex.

Intrathalamic Mechanisms of Visual Attention

The classical model of visual processing emphasizes the lateral geniculate nucleus (LGN) as the major intermediary between the retina and visual cortex. Yet, anatomical findings inspired Francis Crick to suggest an alternative model in which the thalamic reticular nucleus, which envelops the LGN, acts as the "guardian" of visual cortex by modulating LGN activity. Recent work by McAlonan and colleagues supports Crick's hypothesis, thereby enhancing our understanding of the early stages of visual processing.

Noninvasive measurement of the cerebral blood flow response in human lateral geniculate nucleus with arterial spin labeling fMRI

To date, functional magnetic resonance imaging (fMRI) studies of the lateral geniculate nucleus (LGN) have primarily focused on measures of the blood oxygenation level dependent (BOLD) signal. Arterial spin labeling (ASL) is an MRI method that can provide direct measures of functional cerebral blood flow (CBF) changes. Because CBF is a well-defined physiological quantity that contributes to BOLD contrast, CBF measures can be used to improve the quantitative interpretation of fMRI studies. However, due in part to the low intrinsic signal-to-noise ratio of the ASL method, measures of functional CBF changes in the LGN are challenging and have not previously been reported. In this study, we demonstrate the feasibility of using ASL fMRI to measure the CBF response of the LGN to visual stimulation on a 3 T MRI system. The use of background suppression and physiological noise reduction techniques allowed reliable detection of LGN activation in all five subjects studied. The measured percent CBF response during activation ranged from 40 to 100%, assuming no interaction between the left and right LGN.

Recovery from optic neuritis: an ROI-based analysis of LGN and visual cortical areas

Optic neuritis (ON) is the first clinical manifestation in approximately 20% of patients with multiple sclerosis (MS). The inflammation and demyelination of the optic nerve are characterized by symptomatic visual impairment and retrobulbar pain, and associated with decreased visual acuity, decreased colour and contrast sensitivity, delayed visual evoked potentials and visual field defects. Spontaneous recovery of vision typically occurs within weeks or months after onset, depending on the resolution of inflammation, remyelination, restoration of conduction in axons which persist demyelinated and neuronal plasticity in the cortical and subcortical visual pathways. To assess where recovery takes place along the visual pathway, visual activation was studied in the lateral geniculate nucleus (LGN), the main thalamic relay nucleus in the visual pathway and in three areas of the visual cortex: the lateral occipital complexes (LOC), V1 and V2. We conducted a longitudinal functional magnetic resonance imaging (fMRI) study of regions of interest (ROI) of activation in LGN and visual cortex in 19 patients with acute ON at onset, 3 and 6 months from presentation. With fMRI we measured the activation in the ROIs and compared activation during monocular stimulation of the affected and unaffected eye. In the acute phase the activation of LGN during visual stimulation of the affected eye was significantly reduced (P < 0.01) compared to the unaffected eye. This difference in LGN activation between the affected and unaffected eye diminished during recovery, and after 180 days the difference was no longer significant (P = 0.59). The decreased difference during recovery was mainly due to an increase in the fMRI signal when stimulating the affected eye, but included a component of a decreasing fMRI signal from LGN when stimulating the unaffected eye. In LOC, V1 and V2 activation during visual stimulation of the affected eye in the acute phase was significantly reduced (P < 0.01) compared to the unaffected eye, and during recovery the difference diminished with no significant differences left after 180 days. As the pattern of activation in LOC, V1 and V2 resembled the development in LGN we found no evidence of additional cortical adaptive changes. The reduced activation of the LGN to stimulation of the unaffected eye is interpreted as a shift away from early compensatory changes established in the acute phase in LGN and may indicate very early plasticity of the visual pathways.

Decreased Lateral Geniculate Nucleus Activation in Retrogeniculate Hemianopia Demonstrated by Functional Magnetic Resonance Imaging at 4 Tesla

Functional magnetic resonance imaging (fMRI) can detect lateral geniculate nucleus (LGN) activation. We studied LGN function in 5 patients with retrogeniculate homonymous hemianopia using fMRI at 4.0 Tesla during binocular visual stimulation. Decreased activation of visual cortex and LGN on the side of the lesion was observed in all 5 patients. These findings suggest that retrogeniculate lesions are associated with decreased activation of the LGN, due to retrograde degeneration or a functional decrease caused by decreased feedback from ipsilateral visual cortex.

Saccades Differentially Modulate Human LGN and V1 Responses in the Presence and Absence of Visual Stimulation

Saccades occur several times each second in normal human vision. The visual image moves across the retina at high velocity during a saccade, yet no blurring of the visual scene is perceived . Active suppression of visual input may account for this perceptual continuity, but the neural mechanisms underlying such saccadic suppression remain unclear. We used functional MRI to specifically examine responses in the lateral geniculate nucleus (LGN) and primary visual cortex (V1) during saccades. Activity in both V1 and LGN was strongly modulated by saccades. Furthermore, this modulation depended on whether visual stimulation was present or absent. In complete darkness, saccades led to reliable signal increases in V1 and LGN, whereas in the presence of visual stimulation, saccades led to suppression of visually evoked responses. These findings represent unequivocal evidence for saccadic suppression in human LGN and retinotopically defined V1 and are consistent with the earliest site of saccadic suppression lying at or before V1.

Effects of Voxel Size on Detection of Lateral Geniculate Nucleus Activation in Functional Magnetic Resonance Imaging

To study the effect of voxel size on the detection of lateral geniculate nucleus (LGN) activation during visual stimulation using functional magnetic resonance imaging (fMRI) at 1.5 T. Ten normal subjects were scanned during visual stimulation with flashing goggles, four times, with four different voxel sizes. The data were spatially normalized, and LGN activation was identified in the standard coordinates in each subject. When the statistical analysis was performed without global normalization, activation of LGN was detected in both hemispheres in all subjects. However, when global normalization was used, activation of LGN was found in only six subjects in whom the activation could be most frequently detected at the smallest voxel size. Our results suggest that LGN activation can be observed within the range of spatial resolution commonly used in conventional fMRI studies, although postprocessing may affect the detectability of LGN activation in fMRI. These findings may be useful in studying LGN activity in patients with visual disturbance.

Detection of visual activation of lateral geniculate nucleus by positron emission tomography.

Although activation of the lateral geniculate nucleus (LGN) has been shown by functional magnetic resonance imaging, a quantitative evaluation of the activity has not been reported by positron emission tomography (PET). The purpose of this study was to quantify the degree of activation of the LGN and other vision-related structures by visual stimuli as detected by PET. PET activation was induced by a bolus injection of 15O-labelled water (H2(15)O) in six normal volunteers. The regional cerebral blood flow (rCBF) was measured under three conditions: eyes closed, binocular flickering light stimulation, and binocular viewing of a video movie. Single-subject analysis, group analysis, and correlation analysis were performed. Although single-subject analysis did not show significant changes, group analysis revealed a significant increase in rCBF in the left LGN induced by flickering light stimulation ( P<0.01) and video stimulation ( P<0.05). Localization of the activation foci in the LGN agreed with the retinotopic organization of the LGN. Although the LGN is relatively small compared with the resolution of the PET image, visually activated blood flow changes could be determined by H2(15)O PET:

A spherical model for orientation and spatial–frequency tuning in a cortical hypercolumn

A theory is presented of the way in which the hypercolumns in primary visual cortex (V1) are organized to detect important features of visual images, namely local orientation and spatial-frequency. Given the existence in V1 of dual maps for these features, both organized around orientation pinwheels, we constructed a model of a hypercolumn in which orientation and spatial-frequency preferences are represented by the two angular coordinates of a sphere. The two poles of this sphere are taken to correspond, respectively, to high and low spatial-frequency preferences. In Part I of the paper, we use mean-field methods to derive exact solutions for localized activity states on the sphere. We show how cortical amplification through recurrent interactions generates a sharply tuned, contrast-invariant population response to both local orientation and local spatial frequency, even in the case of a weakly biased input from the lateral geniculate nucleus (LGN). A major prediction of our model is that this response is non-separable with respect to the local orientation and spatial frequency of a stimulus. That is, orientation tuning is weaker around the pinwheels, and there is a shift in spatial-frequency tuning towards that of the closest pinwheel at non-optimal orientations. In Part II of the paper, we demonstrate that a simple feed-forward model of spatial-frequency preference, unlike that for orientation preference, does not generate a faithful representation when amplified by recurrent interactions in V1. We then introduce the idea that cortico-geniculate feedback modulates LGN activity to generate a faithful representation, thus providing a new functional interpretation of the role of this feedback pathway. Using linear filter theory, we show that if the feedback from a cortical cell is taken to be approximately equal to the reciprocal of the corresponding feed-forward receptive field (in the two-dimensional Fourier domain), then the mismatch between the feed-forward and cortical frequency representations is eliminated. We therefore predict that cortico-geniculate feedback connections innervate the LGN in a pattern determined by the orientation and spatial-frequency biases of feed-forward receptive fields. Finally, we show how recurrent cortical interactions can generate cross-orientation suppression.

Functional Magnetic Resonance Imaging of Lateral Geniculate Nucleus at 1.5 Tesla

Although activation of the lateral geniculate nucleus has been detected by functional magnetic resonance imaging with magnetic field strengths higher than 2.0 Tesla, there have been no reports of functional magnetic resonance imaging of the lateral geniculate nucleus with the more widely available 1.5 Tesla scanner. The authors used functional magnetic resonance imaging techniques at 1.5 Tesla to detect lateral geniculate nucleus activation in five of seven healthy subjects. This study shows that visual activation of the lateral geniculate nucleus can be obtained with functional magnetic resonance imaging using conventional 1.5 Tesla scanners.

Responses of neurons in neonatal cortex and thalamus to patterned visual stimulation through the naturally closed lids.

In studies of the developing mammalian visual system, it has been axiomatic that visual experience begins with eye-opening. Any role for neuronal activity earlier in development has been attributed to the patterned spontaneous activity found in retina and lateral geniculate nucleus (LGN). Here we show that, as early as 2 wk before eye-opening, visual stimuli presented through the closed eyelids can drive neuronal activity in LGN and striate cortex of the ferret. At this age, spontaneous activity in cortex is much lower than in LGN, and the visual responses of many cortical, but not geniculate, neurons depend on the orientation of a moving grating. Furthermore the selectivity of cortical neurons to the orientation of gratings presented through the closed eyelids improves with age. Thus neuronal activity patterned by visual experience, rather than by spontaneous retinal activity, is present in visual cortex much earlier than previously thought. This could have important implications for the self-organization of visual cortex.