Altered visual contrast gain control is sensitive for idiopathic generalized epilepsies

Objective

Visual hyperexcitability in the form of abnormal contrast gain control has been shown in photosensitive epilepsy and idiopathic generalized epilepsies. We assessed the accuracy and reliability of measures of visual contrast gain control in discerning individuals with idiopathic generalized epilepsies from healthy controls.

Hemispheric lateralization of spatial contrast sensitivity

Visuospatial contrast sensitivity was determined by the Arden grating chart in 23 patients with cerebral infarctions involving the primary visual cortex or visual association cortex. Subjects were classified into three groups according to their lesions: I, 6 patients with unilateral medial occipital or occipitotemporal lesions; II, 6 patients with left lateral parieto-occipital lesions; and III, 11 patients with right lateral parieto-occipital lesions. Contrast sensitivity was markedly reduced in Group III, especially in patients having hemispatial agnosia. Group I patients with hemispatial agnosia showed almost normal contrast sensitivity. Spatial contrast sensitivity appears to be more affected when the lesion has an influence on the nondominant lateral parieto-occipital cortex.     

Cross-species correspondence of spatial contrast sensitivity functions

Spatial contrast sensitivity functions (CSFs) have been obtained for at least 9 species, including man. In the present paper, the shapes and octave band widths of these functions are compared. For most species, the shape of the CSF was an inverted-U, and the full width at half amplitude of the CSFs varied less than one octave. These similarities suggest that there is a close correspondence of the CSFs of these diverse animals; the major difference is the location of each CSF in the spatial frequency domain.     

Contrast gain control and retinogeniculate communication

Visual information processed in the retina is transmitted to primary visual cortex via relay cells in the lateral geniculate nucleus (LGN) of the dorsal thalamus. Although retinal ganglion cells are the primary source of driving input to LGN neurons, not all retinal spikes are transmitted to the cortex. Here, we investigate the relationship between stimulus contrast and retinogeniculate communication and test the hypothesis that both the time course and strength of retinogeniculate interactions are dynamic and dependent on stimulus contrast. By simultaneously recording the spiking activity of synaptically connected retinal ganglion cells and LGN neurons in the cat, we show that the temporal window for retinogeniculate integration and the effectiveness of individual retinal spikes are inversely proportional to stimulus contrast. This finding provides a mechanistic understanding for the phenomenon of augmented contrast gain control in the LGN—a nonlinear receptive field property of LGN neurons whereby response gain during low‐contrast stimulation is enhanced relative to response gain during high‐contrast stimulation. In addition, these results support the view that network interactions beyond the retina play an essential role in transforming visual signals en route from retina to cortex.     

Luminance adaptation increased the contrast sensitivity of retinal ganglion cells

In the present study, the activity changes of chicken retinal ganglion cells in response to light stimuli with defined contrast were investigated, in the presence of various levels of sustained background illumination. Following a step increase of light illumination, the firing rate of most retinal ganglion cells increased abruptly, and then decreased to a steady-state level with a much lower firing rate during the sustained application of light. However, when a test flash was applied, which superimposed the prolonged background illumination, an increased firing rate was observed. Moreover, the neuron firing rate was increased to a greater extent when the intensity of the background illumination was higher. This may suggest that the neuron sensitivity can be modified by the background illumination level, although the neuron firing rate was reduced during sustained illumination.     

Information transmission rate changes of retinal ganglion cells during contrast adaptation

During adaptation to high-contrast stimulation, retinal ganglion cell's responsiveness change is characterized by decreased firing rate and declined sensitivity. In order to examine the modification of information transmission properties of the ganglion cell during this adaptation process, neural activities were recorded extracellularly from the chicken retina using a multi-electrode recording system, and the information transmission rate of the retinal ganglion cells was estimated. The results show that the response entropy and noise entropy of the ganglion cells both decreased during the adaptation process, which resulted in a modest decline of information transmission rate of ganglion cells after several seconds' adaptation. However, due to the decrease of the neuron's firing rate during the adaptation, it is revealed that the information carried by each spike was increased as compared to pre-adaptation, suggesting that retinal ganglion cells' information processing strategies during contrast adaptation may reflect economical principle by promoting each spike more informative. These results also suggest that contrast adaptation and sensitivity rescaling of the visual neurons provide an efficient manner in information transmission and save the system's metabolic cost in the meantime.     

Dietary control of retinal dopamine synthesis

The ingestion of single protein-containing meals raises serum tyrosine levels and the serum tyrosine ratio and brain tyrosine level roughly proportional to the amount of protein consumed in the diet. Retinal tyrosine levels were positively correlated to serum tyrosine and the serum tyrosine ratio after meal consumption. These increases in retinal tyrosine were paralleled by increased synthesis and release of its retinal neurotransmitter product, dopamine.     

Changes of contrast gain in cat dorsal lateral geniculate nucleus by dopamine receptor agonists

The modulatory effects of dopamine (DA) on the contrast gain of retino-geniculate transmission were tested with local micro-iontophoretical application of DA and the DA receptor agonists SKF38393 (SKF, D1/D5) and quinpirole (QUIN, D2/D3/D4) while recording visually induced spike activity of relay cells of the dorsal aspect of cat lateral geniculate nucleus (dLGN) in the anesthetised and paralyzed preparation. DA and QUIN could either facilitate or inhibit visual activity in a dose-dependent fashion: small amounts caused a facilitation while larger quantities resulted in a more (DA) or less (QUIN) strong inhibition. The effect of SKF was almost always suppressive and increased with the amount of drug applied. The absolute change in activity was depending on stimulus contrast and the strength of the elicited response: facilitation and inhibition of activity was proportional to stimulus contrast and response strength and thus resulted in a changed contrast gain. The results indicate that the visual deficits found in Parkinson's disease patients my be not solely related to retinal dysfunctions.     

Octopaminergic modulation of contrast gain adaptation in fly visual motion‐sensitive neurons

Locomotor activity like walking or flying has recently been shown to alter visual processing in several species. In insects, the neuromodulator octopamine is thought to play an important role in mediating state changes during locomotion of the animal [K.D. Longden & H.G. Krapp (2009) J. Neurophysiol., 102 , 3606–3618; (2010) Front. Syst. Neurosci., 4 , 153; S.N. Jung et al. (2011) J. Neurosci., 31 , 9231–9237]. Here, we used the octopamine agonist chlordimeform (CDM) to mimic effects of behavioural state changes on visual motion processing. We recorded from identified motion‐sensitive visual interneurons in the lobula plate of the blowfly Calliphora vicina. In these neurons, which are thought to be involved in visual guidance of locomotion, motion adaptation leads to a prominent attenuation of contrast sensitivity. Following CDM application, the neurons maintained high contrast sensitivity in the adapted state. This modulation of contrast gain adaptation was independent of the activity of the recorded neurons, because it was also present after stimulation with visual motion that did not result in deviations from the neurons’ resting activity. We conclude that CDM affects presynaptic inputs of the recorded neurons. Accordingly, the effect of CDM was weak when adapting and test stimuli were presented in different parts of the receptive field, stimulating separate populations of local presynaptic neurons. In the peripheral visual system adaptation depends on the temporal frequency of the stimulus pattern and is therefore related to pattern velocity. Contrast gain adaptation could therefore be the basis for a shift in the velocity tuning that was previously suggested to contribute to state‐dependent processing of visual motion information in the lobula plate interneurons.     

Disparity-specific spatial interactions: evidence from EEG source imaging

Using cortical source estimation techniques based on high-density EEG and fMRI measurements in humans, we measured how a disparity-defined surround influenced the responses to the changing disparity of a central disk within five visual ROIs: V1, V4, lateral occipital complex (LOC), hMT+, and V3A. The responses in the V1 ROI were not consistently affected either by changes in the characteristics of the surround (correlated or uncorrelated) or by its disparity value, consistent with V1 being responsive only to absolute, not relative, disparity. Correlation in the surround increased the responses in the V4, LOC, and hMT+ ROIs over those measured with the uncorrelated surround. Thus, these extrastriate areas contain neurons that are sensitive to disparity differences. However, their evoked responses did not vary systematically with the surround disparity. Responses in the V3A ROI, in contrast, were increased by correlation in the surround and varied with its disparity. We modeled these V3A responses as attributable to a gain modulation of the absolute disparity response, where the gain amplitude is proportional to the center-surround disparity difference. An additional experiment identified a nonlinear center-surround interaction in V3A that facilitates the responses when center and surround are misaligned but suppresses it when they share the same disparity plane.     

Genetic control of retinal ganglion cell projections.

We have assessed the effects of 15 pigmentation mutations on the development of retinal ganglion cell projections in mice in two ways: (1) by analyzing the pattern of innervation of the ipsilateral lateral geniculate nucleus as mapped in autoradiograms of brains of animals killed 12 days after intravitreal injection of 3H-proline into one eye and (2) by determining the ratio of axonally transported radioactive protein in the contralateral and ipsilateral optic tracts after similar intravitreal injections. Analysis of the ratio of transported protein in the two optic tracts provides a new and useful assay of the degree of decussation in experimental animals. The effects of the mutations on eye pigmentation, whole eye melanin content and relative tyrosinase activity also were examined. The degree of ipsilateral innervation generally correlates with the degree of pigmentation of the retinal pigment epithelium and with tyrosinase activity. However, discrepancies have been found in ch and ce mutants. In these animals the pigment epithelium is well pigmented, and the area of ipsilateral innervation in the lateral geniculate nucleus is extensive, despite a high ratio of label in contralateral to ipsilateral optic tracts and low tyrosinase activity. Furthermore, mice heterozygous for the c2J allele have pigmentation and optic projections that are normal even though tyrosinase is reduced to 40% of normal. The few anomalous results suggest that alternative or additional factors may control optic axon projections.     

The spatial distribution of glutamatergic inputs to dendrites of retinal ganglion cells

The spatial pattern of excitatory glutamatergic input was visualized in a large series of ganglion cells of the rabbit retina, by using particle-mediated gene transfer of an expression plasmid for postsynaptic density 95-green fluorescent protein (PSD95-GFP). PSD95-GFP was confirmed as a marker of excitatory input by co-localization with synaptic ribbons (RIBEYE and kinesin II) and glutamate receptor subunits. Despite wide variation in the size, morphology, and functional complexity of the cells, the distribution of excitatory synaptic inputs followed a single set of rules: 1) the linear density of synaptic inputs (PSD95 sites/linear mum) varied surprisingly little and showed little specialization within the arbor; 2) the total density of excitatory inputs across individual arbors peaked in a ring-shaped region surrounding the soma, which is in accord with high-resolution maps of receptive field sensitivity in the rabbit; and 3) the areal density scaled inversely with the total area of the dendritic arbor, so that narrow dendritic arbors receive more synapses per unit area than large ones. To achieve sensitivity comparable to that of large cells, those that report upon a small region of visual space may need to receive a denser synaptic input from within that space.     

Direct control of firing rate gain by dendritic shunting inhibition

The firing rate gain of neurons, defined as the slope of the relation between input to a neuron and its firing rate, has received considerable attention in the past few years. This has been largely motivated by the many experimental demonstrations of behavior related gain changes in a variety of neural circuits of the CNS. A surprising result was that a prime candidate, shunting inhibition, apparently does not change the firing rate gain of neurons. However, in this paper, we show a physiologically plausible mechanism by which shunting inhibition in the dendritic tree does, in a simple and direct manner, modulate the firing gain of neurons. The effect is due to a strong attenuation of the dendritic current arriving at the soma by shunting dendritic inhibition. Increasing the dendritic inhibitory conductance enhances the attenuation of current flowing from the dendritic to the somatic compartment and thus reduces firing gain. This mechanism relies on known physiological and anatomical properties of CNS neurons and does not require special features such as tunable neural noise inputs. Gain control by the proposed mechanism may prove to be a ubiquitous feature of neural circuit operations and it is readily verifiable experimentally.     

Binaral interaction and centrifugal input enhances spatial contrast in olfactory bulb activation

We used paired-pulse odorant stimulation, with a conditioning stimulus delivered either ipsilateral or contralateral to a test stimulus, to unmask the effects of centrifugal feedback on olfactory bulb responses. In reptiles and mammals there are no direct connections between the paired olfactory bulbs, and thus all information transfer between the olfactory bulbs depends on feedback from retrobulbar structures. We measured odor-induced activity in the turtle olfactory bulb using a voltage-sensitive dye and a 464-element photodiode array, which allowed us to monitor the spatial variation in activation of the olfactory bulb. We found that both contralateral and ipsilateral conditioning stimuli evoked long-lasting inhibition of olfactory bulb activation. In contrast to previous studies using local field potential recording to monitor activity at a single site, we found that this inhibition increased contrast in the spatial patterning of activation over the dorsal surface of the olfactory bulb. Inhibition was also increased when different odorants were used as conditioning and test stimuli, suggesting a role for centrifugal feedback in olfactory discrimination. These results highlight the functional importance of centrifugal feedback and information processing in a broadly distributed olfactory network.     

Cholinergic brainstem sites for gain control of vestibulospinal reflexes in cats

Decerebrate cats were injected with carbachol into the locus coeruleus (LC) or with carbachol or bethanechol into the dorsal pontine reticular formation (pRF) of one side; recordings were made of the tonic contraction of forelimb extensor muscles of both sides and of their responses to sinusoidal roll tilt of the animal. Both drugs had similar effects when injected into the pRF: a decrease in the tonic contraction of limb extensors and a greatly enhanced amplitude and gain with slightly decreased phase lead in the responses to animal tilt of the forelimb extensor, triceps brachii, ipsilateral to the side of injection. Injected into the LC, carbachol produced a response opposite to the above: it increased the tonic contraction of limb extensors ipsilateral to the side of injection, but decreased the amplitude and gain of the EMG responses of limb extensor muscles to labyrinth stimulation induced by sinusoidal tilt. These findings did not depend on changes in posture since they were still observed when postural EMG activity was maintained constant by appropriate changes in static stretch of the muscle. Moreover, the magnitude of the effects increased in a dose-dependent manner. Results suggest that cholinergic activation of dorsal pRF neurons through muscarinic receptors increases the background discharge of medullary inhibitory reticulospinal (RS) system neurons, thus increasing their modulatory influence. Further, it is postulated that cholinergic activation of LC neurons would cause them to inhibit this tonic facilitatory drive by the pRF. Common to both sites of carbachol injection is the increase in phase lag of the EMG response of limb extensors to animal tilt.(ABSTRACT TRUNCATED AT 250 WORDS)     

Contrast and response gain control depend on cortical map architecture

Visual cortical neurons are sensitive to visual stimulus contrast and most cells adapt their sensitivity to the prevailing visual environment. Specifically, they match the steepest region of their contrast response function to the prevailing contrast (contrast gain control), and reduce spike rates to limit saturation (response gain control). Most neurons are also tuned for stimulus orientation, and neurons with similar orientation preference are clustered together into iso‐orientation zones arranged around pinwheels, i.e. points where all orientations are represented. Here we investigated the relationship between the contrast adaptation properties of neurons and their location relative to pinwheels in the orientation preference map. We measured orientation preference maps in cat cortex using optical intrinsic signal imaging. We then characterized the contrast adaptation properties of single neurons located close to pinwheels, in iso‐orientation zones, and at regions in between. We found little evidence of differential contrast sensitivity of neurons adapted to zero contrast. However, after adaptation to their preferred orientation at high contrast, changes in both contrast and response gain were greater for neurons near pinwheels compared with other map regions. Therefore, in the adapted state, which is probably typical during natural viewing, there is a spatial map of contrast sensitivity that is associated with the orientation preference map. This differential adaptation revealed a new dimension of cortical functional organization, linking the contrast adaptation of cells with the orientation preference of their nearest neighbours.