Repetitive Transcorneal Alternating Current Stimulation Reduces Brain Idling State After Long-term Vision Loss.

BACKGROUND: Deafferentation of visual system structures following brain or optic nerve injury leaves cortical areas deprived of visual input. Deprived cortical areas have a reduced sensory information processing and are characterized with localized enhanced or synchronized rhythms believed to represent an "idling state". OBJECTIVE/HYPOTHESIS: We hypothesized that cortical idling can be modified with transcorneal alternating current stimulation (tACS) known to modulate cortical oscillations and thus change the functional state of the deafferented areas. METHODS: tACS was applied in rat model of severe optic nerve crush using a protocol similar to our clinical studies (200 µA, 2-8 Hz) for 5 treatment days right after the lesion and at the chronic stage (3 months later). EEG and VEP were recorded over the visual cortices. In vivo confocal neuroimaging of the retina and histology of the optic nerves were performed. RESULTS: Morphological investigations showed massive retinal ganglion cells death and degeneration of the optic nerves after crush. Visual loss was associated with increased EEG spectral power and lower coherence, indicating an "idling state". Stimulation induced a significant decrease of EEG power towards normal values. These effects were especially pronounced in the chronic stage. CONCLUSION: Our results suggest that alternating current injected via the eye is able to modulate visually deprived brain areas and thus reduce cortical idling.

Standardized F1: a consistent measure of strength of modulation of visual responses to sine-wave drifting gratings.

The magnitude of spike-responses of neurons in the mammalian visual system to sine-wave luminance-contrast-modulated drifting gratings is modulated by the temporal frequency of the stimulation. However, there are serious problems with consistency and reliability of the traditionally used methods of assessment of strength of such modulation. Here we propose an intuitive and simple tool for assessment of the strength of modulations in the form of standardized F1 index, zF1. We define zF1 as the ratio of the difference between the F1 (component of amplitude spectrum of the spike-response at temporal frequency of stimulation) and the mean value of spectrum amplitudes to standard deviation along all frequencies in the spectrum. In order to assess the validity of this measure, we have: (1) examined behavior of zF1 using spike-responses to optimized drifting gratings of single neurons recorded from four 'visual' structures (area V1 of primary visual cortex, superior colliculus, suprageniculate nucleus and caudate nucleus) in the brain of commonly used visual mammal - domestic cat; (2) compared the behavior of zF1 with that of classical statistics commonly employed in the analysis of steady-state responses; (3) tested the zF1 index on simulated spike-trains generated with threshold-linear model. Our analyses indicate that zF1 is resistant to distortions due to the low spike count in responses and therefore can be particularly useful in the case of recordings from neurons with low firing rates and/or low net mean responses. While most V1 and a half of caudate neurons exhibit high zF1 indices, the majorities of collicular and suprageniculate neurons exhibit low zF1 indices. We conclude that despite the general shortcomings of measuring strength of modulation inherent in the linear system approach, zF1 can serve as a sensitive and easy to interpret tool for detection of modulation and assessment of its strength in responses of visual neurons.

Feedback signals from cat's area 21a enhance orientation selectivity of area 17 neurons.

We have studied the contribution of feedback signals originating from one of the "form-processing" extrastriate cortical areas, area 21a (A21a), to orientation selectivity of single neurons in the ipsilateral area 17 (A17). Consistent with previous findings, reversible inactivation (cooling to 5-10 degrees C) of area 21a resulted in a substantial reduction in the magnitude of the maximum response (R (max)) of A17 cells accompanied by some changes in the half-width at half-height of the R (max) (HWHH). By fitting model functions to the neurons' response profiles we found that in the vast majority of orientation-tuned A17 cells tested (30/39, 77%), inactivation of A21a resulted in a "flattening" of their orientation-tuning curves. It is characterised by a substantial reduction in the R (max) associated with either a broadening of the orientation-tuning curves (17 cells) or a relatively small reduction (12 cells) or no change (1 cell) in the HWHH. When the "flattening" effect was quantified using a simple ratio index or R/W, defined as R (max)/HWHH, we found that R/W was significantly reduced during inactivation of A21a. The change in R/W is strongly correlated with the change in the maximum slope of the orientation-tuning curves. Furthermore, analysis of response variability indicates that "signal-to-noise" ratio of the responses of A17 neurons decreases during inactivation of A21a. Our results suggest that the predominately excitatory feedback signals originating from A21a play a role in enhancing orientation selectivity of A17 neurons and hence are likely to improve overall orientation discriminability.

Spatial and temporal visual properties of single neurons in the suprageniculate nucleus of the thalamus.

The spatial and temporal visual sensitivity to drifting sinusoidal gratings was studied in 105 neurons of the suprageniculate nucleus of the feline thalamus. Extracellular single-unit recordings were performed in halothane-anesthetized, immobilized, artificially ventilated cats. Most suprageniculate nucleus cells were strongly sensitive to the direction of drifting gratings. The suprageniculate nucleus units had a clear preference for very low spatial frequencies with a mean of 0.05 cycle/deg. The spatial resolution was also very low with a mean of 0.16 cycle/deg. Most of the cells displayed low-pass spatial tuning characteristics, while the remainder of the units were band-pass tuned. The suprageniculate nucleus units were extremely narrowly tuned, to spatial frequencies with a mean spatial bandwidth of 1.07 octaves. A majority of the units responded optimally to high temporal frequencies, with a mean of 8.53 Hz. The temporal frequency tuning functions predominantly revealed a band-pass character, with a mean temporal bandwidth of 1.66 octaves. These results demonstrate that the neurons in the suprageniculate nucleus display particular spatial and temporal characteristics. The spatial and temporal tuning properties of the suprageniculate nucleus neurons are very similar to those of the superior colliculus and the anterior ectosylvian cortex, structures that provide the main visual afferentation toward the suprageniculate nucleus. This suggests their common function in motion perception, and especially in the recording of movements of the visual environment relative to the body, and the related behavioral action.

Laminar differences in plasticity in area 17 following retinal lesions in kittens or adult cats.

Circumscribed retinal lesions in adult cats result in a reorganization of circuitry in area 17 such that neurons in the lesion projection zone (LPZ) can now be activated, not from their original receptive fields (RFs) but from regions of normal retina adjacent to the lesion ('ectopic' RFs). We have studied this phenomenon further by making circumscribed monocular retinal lesions in 8-week-old kittens and recording responses to visual stimuli of neurons in the LPZ of area 17 when these cats reached adulthood. These responses have been compared with those in adult-lesioned cats either of relatively short postlesion survival (2-24 weeks) or long postlesion survival (3.5-4.5 years). In both kitten-lesioned and adult-lesioned animals most LPZ neurons recorded from the supragranular layers (II and III) not only exhibited new ectopic RFs when stimuli were presented via the lesioned eye but the RF properties (e.g. the sizes of excitatory RFs, orientation and direction selectivities, velocity preferences and upper cut-off velocities) were often indistinguishable from those seen when stimuli were presented via the nonlesioned eye. Similarly, in both kitten-lesioned and adult-lesioned animals, most LPZ neurons recorded from the granular and infragranular layers (IV, V, VI), like those recorded from the supragranular layers, were binocular. However, in adult-lesioned but not in kitten-lesioned animals, the responses and the upper cut-off velocities of LPZ cells recorded from the granular and infragranular layers to stimuli presented via ectopic RFs tended to be, respectively, substantially weaker and lower than those for stimuli presented via the nonlesioned eye. The age-related laminar differences in reorganizational plasticity of cat striate cortex correlate with the lamino-temporal pattern of distribution of N-methyl-d-aspartate glutamate receptors in striate cortex.

Topographic reorganization in area 18 of adult cats following circumscribed monocular retinal lesions in adolescence.

Circumscribed laser lesions were made in the nasal retinae of one eye in adolescent cats. Ten to sixteen months later, about 80 % of single neurones recorded in the lesion projection zone (LPZ) of contralateral area 18 (parastriate cortex, area V2) were binocular but when stimulated via the lesioned eye had ectopic discharge fields (displaced to normal retina in the vicinity of the lesion). Although the clear majority of binocular cells recorded from the LPZ responded with higher peak discharge rates to stimuli presented via the non-lesioned eye, the orientation and direction selectivities as well as preferred and upper cut-off velocities for stimuli presented through either eye were very similar. Furthermore, the sizes of the ectopic discharge fields of binocular cells recorded from the LPZ were not significantly different from those of their counterparts plotted via the non-lesioned eye. Thus, monocular retinal lesions performed in adolescent cats induce topographic reorganization in the LPZ of area 18. Although a similar reorganization occurs in area 17 (striate cortex, area V1) of cats in which monocular retinal lesions were made either in adulthood or adolescence, in view of the very different velocity response profiles of ectopic discharge fields in areas 17 and those in area 18, it appears that ectopic discharge fields in area 17 are largely independent of excitatory feedback input from area 18.

The spatial substructure of visual receptive fields in the cat's superior colliculus.

Although the direction selective properties of the superficial layer cells of the cat's superior colliculus have been extensively studied, the mechanisms underlying this property remain controversial. With the aim to understand the mechanism(s) underlying directional selectivity of collicular neurons we examined the substructure of their visual receptive fields. 1. The strength of cell responses and the direction selectivity indices varied in relation to the location of the tested region within the receptive field and the amplitude of stimulus movement. 2. Decrease of the amplitude of motion resulted in a decrease of direction selectivity index both in the group of direction-selective cells and in the group of cells classified as direction nonselective but with a directional bias. 3. The decrease of direction selectivity for small amplitude movement resulted mainly from increase in the magnitude of response in the nonpreferred direction of movement. 4. These results suggest that the receptive fields of most collicular cells are composed of subregions with different response profiles and indicate that inhibitory mechanisms dictate direction selectivity of collicular cells.

Convergence of Y and non-Y channels onto single neurons in the superior colliculi of the cat.

Receptive field properties of single neurons in the cat superior colliculus were examined following selective conduction-block of Y-type fibers in contralateral optic nerve. Although the responses evoked by photic stimuli presented via the Y-blocked eye were significantly weaker than those evoked by stimuli presented via the normal eye, > 85% of collicular cells were binocular. Furthermore, when binocular cells were stimulated via the Y-blocked eye their median upper cut-off velocity (100 degrees /s) was significantly lower than that (400 degrees /s) for stimuli presented via the normal eye. Thus, there is a substantial degree of excitatory convergence of Y- and non-Y- information channels on single collicular neurons and the responses to high velocity of motion appear to depend on the integrity of Y-type input.

Modulatory influence of feedback projections from area 21a on neuronal activities in striate cortex of the cat.

We have examined the influence of 'feedback' projections from extrastriate visual cortical area 21a on the responses of neurons in area 17 of the cat, by cooling area 21a to 5-10 degrees C while the temperature over the recording sites was kept at 36 degrees C. Orientation, direction and length selectivities as well as contrast sensitivity were tested before and during cooling and after rewarming of area 21a. Overall, for the sample of cells recorded from the part of area 17 visuotopically corresponding to area 21a, the 'spontaneous' activity (at background illumination of 1 cd/m(2)) and the responsiveness to visual stimuli of standard contrast (15) were significantly reduced by inactivation of area 21a. In about half of the cells inactivation of area 21a affected substantially the sharpness of orientation-tuning. However, only in a minority of the cells were the direction or length selectivities significantly affected by inactivation of area 21a. Thus (i) the feedback projections from area 21a appear to exert mainly an excitatory influence on the background activity and responsiveness of area 17 cells and (ii) only in subgroups of area 17 cells does the feedback activity originating from area 21a appear to modulate specifically certain receptive field properties.

Plasticity in adult cat visual cortex (area 17) following circumscribed monocular lesions of all retinal layers.

1. In eight adult cats intense, sharply circumscribed, monocular laser lesions were used to remove all cellular layers of the retina. The extents of the retinal lesions were subsequently confirmed with counts of alpha-ganglion cells in retinal whole mounts; in some cases these revealed radial segmental degeneration of ganglion cells distal to the lesion. 2. Two to 24 weeks later, area 17 (striate cortex; V1) was studied electrophysiologically in a standard anaesthetized, paralysed (artificially respired) preparation. Recording single- or multineurone activity revealed extensive topographical reorganization within the lesion projection zone (LPZ). 3. Thus, with stimulation of the lesioned eye, about 75 % of single neurones in the LPZ had 'ectopic' visual discharge fields which were displaced to normal retina in the immediate vicinity of the lesion. 4. The sizes of the ectopic discharge fields were not significantly different from the sizes of the normal discharge fields. Furthermore, binocular cells recorded from the LPZ, when stimulated via their ectopic receptive fields, exhibited orientation tuning and preferred stimulus velocities which were indistinguishable from those found when the cells were stimulated via the normal eye. 5. However, the responses to stimuli presented via ectopic discharge fields were generally weaker (lower peak discharge rates) than those to presentations via normal discharge fields, and were characterized by a lower-than-normal upper velocity limit. 6. Overall, the properties of the ectopic receptive fields indicate that cortical mechanisms rather than a retinal 'periphery' effect underlie the topographic reorganization of area 17 following monocular retinal lesions.

Velocity response profiles of collicular neurons: parallel and convergent visual information channels.

We have recorded from single neurons in the retinorecipient layers of the superior colliculus of the cat. We distinguished several functionally distinct groups of collicular neurons on the basis of their velocity response profiles to photic stimuli. The first group was constituted by cells responding only to photic stimuli moving at slow-to-moderate velocities across their receptive fields (presumably receiving strong excitatory W-type input but not, or only subthreshold, Y-type input). These cells were recorded throughout the stratum griseum superficiale and stratum opticum and constituted 50% of our sample. The second group of cells exhibited excitatory responses only at moderate and fast velocities (presumably receiving excitatory Y-type but not W-type input). These cells constituted only about 7% of the sample and were located principally in the lower stratum griseum superficiale. The third group of cells was constituted by cells excited over the entire range of velocities tested (1-2000 /s) and presumably received substantial excitatory input from both W- and Y-channels. These cells constituted almost 26% of our sample and were located in the lower stratum griseum superficiale, stratum opticum and the upper part of the stratum griseum intermediale. Overall, cells receiving excitatory Y-type input, i.e. the sum of group two and group three cells, constituted about a third of the sample and their excitatory discharge fields were significantly larger than those of cells receiving only W-type input. A fourth distinct group of collicular neurons was also constituted by cells responding over a wide range of stimulus velocities. These cells were excited by slowly moving stimuli, while fast-moving photic stimuli evoked purely suppressive responses. The excitatory discharge fields of these cells (presumably, indicating the spatial extent of the W-input) were located within much larger inhibitory fields, the extent of which presumably indicates the spatial extent of the Y-input. These low-velocity-excitatory/high-velocity-suppressive cells were recorded from the stratum griseum superficiale, stratum opticum and stratum griseum intermediale and constituted about 17% of the sample. The existence of low-velocity-excitatory/high-velocity-suppressive cells in the mammalian colliculus has not been previously reported. Low-velocity-excitatory/high-velocity-suppressive cells might play an important role in activating "fixation/orientation" and "saccade" premotor neurons recorded by others in the intermediate and deep collicular layers. Overall, in the majority (57%) of collicular neurons in our sample there was no indication of a convergence of W- and Y-information channels. However, in a substantial minority of collicular cells (about 43% of the sample) there was clear evidence of such convergence and about 40% of these (low-velocity-excitatory/high-velocity-suppressive cells) appear to receive excitatory input from the W-channel and inhibitory input from the Y-channel.

Summation effects in receptive fields of the cat's pretectal neurons to stationary and moving visual stimuli.

1. Numerous investigations have shown that the cat's pretectal region (PR) is involved in performance of various visual habits, visually guided behaviour and learning processes. Thus, visually driven PR neurons must have abilities to integrate incoming sensory information. 2. Responses of 102 PR neurons to moving and stationary visual stimuli were investigated in cats. Special attention was paid to the comparative characteristics of summation processes in the same neuron elicited by stationary and moving visual stimuli. 3. The results indicate that only a small proportion (20%) of pretectal neurons revealed similar courses of summation for stationary and moving stimuli. The great majority of neurons (about 80%) showed differentiated courses of summation, depending on the type of visual stimuli used. 4. These data indicate that there are probably discrete mechanisms in the PR which contribute to integration of sensory information in the visually sensitive cells according to the different types of visual stimuli used.

Influence of the intertectal connection upon visual responses in the cat's superior colliculus.

Visual responses of single units in the superficial layers of the superior colliculus were examined in cats with pretrigeminal brainstem transections and lesions in the contralateral superior colliculus. The percentage of direction selective cells was decreased in lesioned as compared to non-lesioned cats. This effect may be a result of the elimination of suppression from the contralateral superior colliculus as well as disturbance of the projections from other structures of the contralateral hemisphere.