Interictal Activity Is Associated With Slower Binocular Rivalry in Idiopathic Generalized Epilepsy

Objective: Perceptual alternations evoked by binocular rivalry (BR) reflect cortical dynamics strongly dependent on the excitatory–inhibitory balance, suggesting potential utility as a biomarker for epileptogenesis. Therefore, we investigated the characteristics of BR in patients with idiopathic generalized epilepsy (IGE) and potential associations with clinical variables.Methods: Sixty-two healthy controls (HCs) and 94 IGE patients completed BR task. Perceptual alternation rates were compared between HC and IGE groups as well as among the HC group and IGE patients stratified according to the presence or absence of interictal activity on the ambulatory electroencephalogram (EEG), termed the abnormal ambulatory EEG group (AB-AEEG, n = 64) and normal ambulatory EEG group (N-AEEG, n = 30), respectively.Results: The IGE patients demonstrated a slower rate of BR perceptual alternation than HC subjects (t = −4.364, p < 0.001). The alternation rate also differed among the HC, AB-AEEG, and N-AEEG groups (F = 44.962, df = 2, p < 0.001), and post hoc comparisons indicated a significantly slower alternation rate in the AB-AEEG group compared with the N-AEEG and HC groups (0.28 vs. 0.46, and 0.43 Hz). Stepwise linear regression revealed positive correlations between the BR alternation rate and both the ambulatory EEG status (β, 0.173; standard error, 0.022 p < 0.001) and Montreal Cognitive Assessment score (β, 0.013; standard error, 0.004; p = 0.003). Receiver operating characteristic curve analysis of the BR alternation rate distinguished AB-AEEG from N-AEEG subjects with 90.00% sensitivity and 76.90% specificity (area under the curve = 0.881; 95% confidence interval = 0.801– 0.961, cut-off = 0.319). Alternatively, Montreal Cognitive Assessment score did not accurately distinguish AB-AEEG from N-AEEG subjects and the area under the receiver operating characteristic curve combining the BR alternation rate and Montreal Cognitive Assessment score was not markedly larger than that of the BR alternation rate alone (0.894, 95% confidence interval = 0.822–0.966, p < 0.001). K-fold cross-validation was used to evaluate the predictive performance of BR alternation rate, MoCA score, and the combination of both, which yielded average AUC values of 0.870, 0.584 and 0.847, average sensitivity values of 89.36, 92.73, and 91.28%, and average specificity values of 62.25, 13.42, and 61.78%, respectively. The number of interictal epileptiform discharges was significantly correlated with the alternation rate in IGE patients (r = 0.296, p = 0.018). A forward stepwise linear regression model identified the number of interictal epileptiform discharges (β, 0.001; standard error, 0.001; p = 0.025) as an independent factor associated with BR alternation rate in these patients.Conclusion: These results suggest that interictal epileptiform discharges are associated with disruptions in perceptual awareness, and that the BR may be a useful auxiliary behavioral task to diagnosis and dynamically monitor IGE patients with interictal discharge.

A238 ABSENCE OF AGE-RELATED MEMORY DECLINE IN GERM-FREE MICE

Background Age-associated deterioration of cognitive function and memory capacity occur in a variety of mammals, from humans to rodents. For example, significant memory deficits have been reported in conventionally raised (SPF) old mice compared to conventionally raised young mice submitted to a spatial memory task (Prevot et al., Mol Neuropsychiatry 2019). Microbiota to brain signaling is now well established in mice, but the extent to which this influences age-related memory decline is unknown. Aims Our project aims to determine whether the intestinal microbiota contributes to age-related changes in brain function. We address the hypothesis that age-related cognitive decline is attenuated in the absence of the intestinal microbiota. Methods We studied locomotor behavior and spatial memory performance in young germ-free (GF) mice (2–3 months of age, n=24) and senescent GF mice (13–27 months old, n=22) maintained in axenic conditions, and compared them to conventionally raised (SPF) mice. We used the Y-maze test based on a spontaneous alternations task to assess cognition, with alternation rate as a proxy of spatial working memory performance. The locomotor activity was measured using the open-field test. Results GF old mice traveled less distance (458.9 cm) than GF young mice (875.7 cm, p < 0.001) but these differences in locomotor activity did not influence spatial memory performance. Indeed, both GF old and GF young mice had an identical alternation rate of 73.3% (p > 0.05). This contrasted with the memory impairment found in old SPF mice that displayed lower alternation rate of 58.3%, compared to that found in young SPF mice (76.2%, p = 0.13). Conclusions We conclude that the absence of age-related memory decline in germ-free mice is consistent with a role for the microbiota in the cognitive decline associated with aging, likely through action on the immune system, well documented in SPF mice (Thevaranjan et al., Cell Host & Microbe 2017). We propose that novel microbiota-targeted therapeutic strategies may delay or prevent the cognitive decline of aging. Funding Agencies CIHRBalsam Family Foundation

Fast cyclic stimulus flashing modulates perception of bi-stable figure

Many experiments have demonstrated that the rhythms in the brain influence the initial perceptual information processing. We investigated whether the alternation rate of the perception of a Necker cube depends on the frequency and duration of a flashing Necker cube. We hypothesize that synchronization between the external rhythm of a flashing stimulus and the internal rhythm of neuronal processing should change the alternation rate of a Necker cube. Knowing how a flickering stimulus with a given frequency and duration affects the alternation rate of bistable perception, we could estimate the frequency of the internal neuronal processing. Our results show that the perception time of the dominant stimulus depends on the frequency or duration of the flashing stimuli. The duration of the stimuli, at which the duration of the perceived image was maximal, was repeated periodically at 4 ms intervals. We suppose that such results could be explained by the existence of an internal rhythm of 125 cycles/s for bistable visual perception. We can also suppose that it is not the stimulus duration but the precise timing of the moments of switching on of external stimuli to match the internal stimuli which explains our experimental results. Similarity between the effects of flashing frequency on alternation rate of stimuli perception in present and previously performed experiment on binocular rivalry support the existence of a common mechanism for binocular rivalry and monocular perception of ambiguous figures.

Fast cyclic stimulus flashing modulates perception of bi-stable figure

Many experiments have demonstrated that the rhythms in the brain influence an initial information processing. We investigated whether the alternation rate of the perception of a Necker cube depended on the degree of synchronization between two streams of spikes, one stemming from an external flashing image and the other from the action of an internal impulse stream. Knowing how a flickering stimulus with a given frequency and duration affects the alternation rate of bi-stable perception we could estimate properties of the internal signal. As the internal spike frequency is difficult to control, we varied the frequency of the flicker stimulus. Our results show that the duration of the dominant stimulus perception depends on the frequency or duration of the flashing stimuli. The values of the stimuli, at which the changes of the duration of the perceived image was maximal, we have called ‘extremal’. While changing the flash duration, the extremal parameters repeated periodically at 4ms intervals. Increasing the duration of the extremal stimuli by less than 4 ms shortens the duration of the dominant stimulus perception. Hence we may conclude that it is not the stimulus duration but the accurate coincidence (timing) of the moments of switching on of external stimuli to match the internal stimuli which explains our experimental results.

Fast cyclic stimulus flashing modulates perception of bi-stable figure

Many experiments have demonstrated that the rhythms in the brain influence an initial information processing. We investigated whether the alternation rate of the perception of a Necker cube depended on the degree of synchronization between two streams of spikes, one stemming from an external flashing image and the other from the action of an internal impulse stream. Knowing how a flickering stimulus with a given frequency and duration affects the alternation rate of bi-stable perception we could estimate properties of the internal signal. As the internal spike frequency is difficult to control, we varied the frequency of the flicker stimulus. Our results show that the duration of the dominant stimulus perception depends on the frequency or duration of the flashing stimuli. The values of the stimuli, at which the changes of the duration of the perceived image was maximal, we have called ‘extremal’. While changing the flash duration, the extremal parameters repeated periodically at 4ms intervals. Increasing the duration of the extremal stimuli by less than 4 ms shortens the duration of the dominant stimulus perception. Hence we may conclude that it is not the stimulus duration but the accurate coincidence (timing) of the moments of switching on of external stimuli to match the internal stimuli which explains our experimental results.

Noise-Induced Alternations in an Attractor Network Model of Perceptual Bistability

When a stimulus supports two distinct interpretations, perception alternates in an irregular manner between them. What causes the bistable perceptual switches remains an open question. Most existing models assume that switches arise from a slow fatiguing process, such as adaptation or synaptic depression. We develop a new, attractor-based framework in which alternations are induced by noise and are absent without it. Our model goes beyond previous energy-based conceptualizations of perceptual bistability by constructing a neurally plausible attractor model that is implemented in both firing rate mean-field and spiking cell-based networks. The model accounts for known properties of bistable perceptual phenomena, most notably the increase in alternation rate with stimulation strength observed in binocular rivalry. Furthermore, it makes a novel prediction about the effect of changing stimulus strength on the activity levels of the dominant and suppressed neural populations, a prediction that could be tested with functional MRI or electrophysiological recordings. The neural architecture derived from the energy-based model readily generalizes to several competing populations, providing a natural extension for multistability phenomena.