Human visual gamma for color stimuli: When LGN drive is equalized, red is not special

Strong gamma-band oscillations in primate early visual cortex can be induced by spatially homogeneous, high-contrast stimuli, such as color surfaces. Compared to other hues, particularly strong gamma oscillations have been reported for red stimuli. However, precortical color processing and the resultant strength of input to V1 has often not been fully controlled for. This leaves the possibility that stronger responses to some hues were due to differences in V1 input strength. We presented stimuli that had equal luminance and color contrast levels in a color coordinate system based on color responses of the lateral geniculate nucleus, the main input source for area V1. With these stimuli, we recorded magnetoencephalography in 30 human subjects. We found narrowband color-induced gamma oscillations in early visual cortex, which, contrary to previous reports, did not differ between red and green stimuli of equal L-M cone contrast. Notably, blue stimuli with contrast exclusively on the S cone axis induced very weak gamma responses, as well as smaller event-related fields and poorer change detection performance. The strength of human color gamma responses could be well explained by the strength of thalamic input induced by each hue and does not show a clear red bias when this input strength is properly equalized.

The beta component of gamma-band auditory steady-state responses in patients with schizophrenia

The mechanisms underlying circuit dysfunctions in schizophrenia (SCZ) remain poorly understood. Auditory steady-state responses (ASSRs), especially in the gamma and beta band, have been suggested as a potential biomarker for SCZ. While the reduction of 40 Hz power for 40 Hz drive has been well established and replicated in SCZ patients, studies are inconclusive when it comes to an increase in 20 Hz power during 40 Hz drive. There might be several factors explaining the inconsistencies, including differences in the sensitivity of the recording modality (EEG vs MEG), differences in stimuli (click-trains vs amplitude-modulated tones) and large differences in the amplitude of the stimuli. Here, we used a computational model of ASSR deficits in SCZ and explored the effect of three SCZ-associated microcircuit alterations: reduced GABA activity, increased GABA decay times and NMDA receptor hypofunction. We investigated the effect of input strength on gamma (40 Hz) and beta (20 Hz) band power during gamma ASSR stimulation and saw that the pronounced increase in beta power during gamma stimulation seen experimentally could only be reproduced in the model when GABA decay times were increased and only for a specific range of input strengths. More specifically, when the input was in this specific range, the rhythmic drive at 40 Hz produced a strong 40 Hz rhythm in the control network; however, in the ‘SCZ-like’ network, the prolonged inhibition led to a so-called ‘beat-skipping’, where the network would only strongly respond to every other input. This mechanism was responsible for the emergence of the pronounced 20 Hz beta peak in the power spectrum. The other two microcircuit alterations were not able to produce a substantial 20 Hz component but they further narrowed the input strength range for which the network produced a beta component when combined with increased GABAergic decay times. Our finding that the beta component only existed for a specific range of input strengths might explain the seemingly inconsistent reporting in experimental studies and suggests that future ASSR studies should systematically explore different amplitudes of their stimuli. Furthermore, we provide a mechanistic link between a microcircuit alteration and an electrophysiological marker in schizophrenia and argue that more complex ASSR stimuli are needed to disentangle the nonlinear interactions of microcircuit alterations. The computational modelling approach put forward here is ideally suited to facilitate the development of such stimuli in a theory-based fashion.

Experience-dependent weakening of callosal synaptic connections in the absence of postsynaptic FMRP

Reduced structural and functional interhemispheric connectivity correlates with the severity of Autism Spectrum Disorder (ASD) behaviors in humans. Little is known of how ASD-risk genes regulate callosal connectivity. Here we show that Fmr1, whose loss-of-function leads to Fragile X Syndrome (FXS), cell autonomously promotes maturation of callosal excitatory synapses between somatosensory barrel cortices in mice. Postnatal, cell-autonomous deletion of Fmr1 in postsynaptic Layer (L) 2/3 or L5 neurons results in a selective weakening of AMPA receptor- (R), but not NMDA receptor-, mediated callosal synaptic function, indicative of immature synapses. Sensory deprivation by contralateral whisker trimming normalizes callosal input strength, suggesting that experience-driven activity of postsynaptic Fmr1 KO L2/3 neurons weakens callosal synapses. In contrast to callosal inputs, synapses originating from local L4 and L2/3 circuits are normal, revealing an input-specific role for postsynaptic Fmr1 in regulation of synaptic connectivity within local and callosal neocortical circuits. These results suggest direct cell autonomous and postnatal roles for FMRP in development of specific cortical circuits and suggest a synaptic basis for long-range functional underconnectivity observed in FXS patients.

Cascades of Periodic Solutions in a Neural Circuit With Delays and Slow-Fast Dynamics

We analyse periodic solutions in a system of four delayed differential equations forced by periodic inputs representing two competing neural populations connected with fast mutual excitation and slow delayed inhibition. The combination of mechanisms generates a rich dynamical structure that we are able to characterize using slow-fast dissection and a binary classification of states. We previously proved the existence conditions of all possible states 1:1 locked to the inputs and applied this analysis to the tracking of the rhythms perceived when listening to alternating sequences of low and high tones. Here we extend this analysis using analytical and computational tools by proving the existence a set of n:1 periodically locked states and their location in parameter space. Firstly we examine cycle skipping states and find that they accumulate in an infinite cascade of period-incrementing bifurcations with increasing periods for decreasing values of the local input strength. Secondly we analyse periodic solutions that alternate between 1:1 locked states that repeat after an integer multiple of the input period (swapping states). We show that such states accumulate in similar bifurcation cascades with decreasing values of the lateral input strength. We report a parameter-dependent scaling constant for the ratio of widths of successive regions in the cascades, which generalises across cycle skipping and swapping states. The periodic states reported here - emergent behaviours in the model - can be linked to known phenomena in auditory perception that are beyond the original scope of the model’s design.

Perceptual rivalry with vibrotactile stimuli

In perceptual rivalry, ambiguous sensory information leads to dynamic changes in the perceptual interpretation of fixed stimuli. This phenomenon occurs when participants receive sensory stimuli that support two or more distinct interpretations; this results in spontaneous alternations between possible perceptual interpretations. Perceptual rivalry has been widely studied across different sensory modalities including vision, audition, and to a limited extent, in the tactile domain. Common features of perceptual rivalry across various ambiguous visual and auditory paradigms characterize the randomness of switching times and their dependence on input strength manipulations (Levelt’s propositions). It is still unclear whether the general characteristics of perceptual rivalry are preserved with tactile stimuli. This study aims to introduce a simple tactile stimulus capable of generating perceptual rivalry and explores whether general features of perceptual rivalry from other modalities extend to the tactile domain. Our results confirm that Levelt’s proposition II extends to tactile bistability, and that the stochastic characteristics of irregular perceptual alternations agree with non-tactile modalities. An analysis of correlations between subsequent perceptual phases reveals a significant positive correlation at lag 1 (as found in visual bistability), and a negative correlation for lag 2 (in contrast with visual bistability).

The beta component of gamma-band auditory steady-state responses in patients with schizophrenia

The mechanisms underlying circuit dysfunctions in schizophrenia (SCZ) remain poorly understood. Auditory steady-state responses (ASSRs), especially in the gamma and beta band, have been suggested as a potential biomarker for SCZ. While the reduction of 40Hz power for 40Hz drive has been well established and replicated in SCZ patients, studies are inconclusive when it comes to an increase in 20Hz power during 40Hz drive. There might be several factors explaining the inconsistencies, including differences in the sensitivity of the recording modality (EEG vs MEG), differences in stimuli (click-trains vs amplitude-modulated tones) and large differences in the amplitude of the stimuli. Here, we used a computational model of ASSR deficits in SCZ and explored the effect of three SCZ-associated microcircuit alterations: reduced GABA activity, increased GABA decay times and NMDA receptor hypofunction. We investigated the effect of input strength on gamma (40 Hz) and beta (20 Hz) band power during gamma ASSR stimulation and saw that the pronounced increase in beta power during gamma stimulation seen experimentally could only be reproduced in the model when GABA decay times were increased and only for a specific range of input strengths. More specifically, when the input was in this specific range, the rhythmic drive at 40Hz produced a strong 40Hz rhythm in the control network; however, in the ‘SCZ-like’ network, the prolonged inhibition led to a so-called ‘beat-skipping’, where the network would only strongly respond to every other input. This mechanism was responsible for the emergence of the pronounced 20Hz beta peak in the power spectrum. The other two microcircuit alterations were not able to produce a substantial 20 Hz component but they further narrowed the input strength range for which the network produced a beta component when combined with increased GABAergic decay times. Our finding that the beta component only existed for a specific range of input strengths might explain the seemingly inconsistent reporting in experimental studies and suggests that future ASSR studies should systematically explore different amplitudes of their stimuli. Furthermore, we provide a mechanistic link between a microcircuit alterations and an electrophysiological marker in schizophrenia and argue that more complex ASSR stimuli are needed to disentangle the nonlinear interactions of microcircuit alterations. The computational modelling approach put forward here is ideally suited to facilitate the development of such stimuli in a theory-based fashion.

Perceptual rivalry with vibrotactile stimuli

In perceptual rivalry, ambiguous sensory information leads to dynamic changes in the perceptual interpretation of fixed stimuli. This phenomenon occurs when participants receive sensory stimuli that support two or more distinct interpretations; this results in spontaneous alternations between possible perceptual interpretations. Perceptual rivalry has been widely studied across different sensory modalities including vision, audition and, to a limited extent, in the tactile domain. Common features of perceptual rivalry across various ambiguous visual and auditory paradigms characterise the randomness of switching times and their dependence on input strength manipulations (Levelt’s propositions). It is still unclear whether general characteristics of perceptual rivalry are preserved with tactile stimuli. This study aims to introduce a simple tactile stimulus capable of generating perceptual rivalry and explores whether general features of perceptual rivalry from other modalities extend to the tactile domain.

Excitation/inhibition imbalance and impaired neurogenesis in neurodevelopmental and neurodegenerative disorders

The excitation/inhibition (E/I) balance controls the synaptic inputs to prevent the inappropriate responses of neurons to input strength, and is required to restore the initial pattern of network activity. Various neurotransmitters affect synaptic plasticity within neural networks via the modulation of neuronal E/I balance in the developing and adult brain. Less is known about the role of E/I balance in the control of the development of the neural stem and progenitor cells in the course of neurogenesis and gliogenesis. Recent findings suggest that neural stem and progenitor cells appear to be the target for the action of GABA within the neurogenic or oligovascular niches. The same might be true for the role of neuropeptides (i.e. oxytocin) in neurogenic niches. This review covers current understanding of the role of E/I balance in the regulation of neuroplasticity associated with social behavior in normal brain, and in neurodevelopmental and neurodegenerative diseases. Further studies are required to decipher the GABA-mediated regulation of postnatal neurogenesis and synaptic integration of newly-born neurons as a potential target for the treatment of brain diseases.

Biased competition in the absence of input bias revealed through corticostriatal computation

Classical accounts of biased competition require an input bias to resolve the competition between neuronal ensembles driving downstream processing. However, flexible and reliable selection of behaviorally relevant ensembles can occur with unbiased stimulation: striatal D1 and D2 spiny projection neurons (SPNs) receive balanced cortical input, yet their activity determines the choice between GO and NO-GO pathways in the basal ganglia. We here present a corticostriatal model identifying three mechanisms that rely on physiological asymmetries to effect rate- and time-coded biased competition in the presence of balanced inputs. First, tonic input strength determines which one of the two SPN phenotypes exhibits a higher mean firing rate. Second, low-strength oscillatory inputs induce higher firing rate in D2 SPNs but higher coherence between D1 SPNs. Third, high-strength inputs oscillating at distinct frequencies can preferentially activate D1 or D2 SPN populations. Of these mechanisms, only the latter accommodates observed rhythmic activity supporting rule-based decision making in prefrontal cortex.

Biased competition in the absence of input bias: predictions from corticostriatal computation

Classical accounts of biased competition (BC) require an input bias to resolve the competition between neuronal ensembles driving downstream processing. However, flexible and reliable selection of behaviorally-relevant ensembles can occur with unbiased stimulation: striatal D1 and D2 spiny projecting neurons (SPNs) receive balanced cortical input, yet their activity determines the choice between GO and NO-GO pathways in the basal ganglia. We present a corticostriatal model identifying three mechanisms that rely on physiological asymmetries to effect rate- and time-coded BC in the presence of balanced inputs. First, tonic input strength determines which SPN phenotype exhibit higher mean firing rate (FR). Second, low strength oscillatory inputs induce higher FR in D2 SPNs but higher coherence between D1 SPNs. Third, high strength inputs oscillating at distinct frequencies preferentially activate D1 or D2 SPN populations. Of these mechanisms, the latter accommodates observed rhythmic activity supporting rule-based decision making in prefrontal cortex.