Sensory Drive Modifies Brain Dynamics and the Temporal Integration Window.

Perception is suggested to occur in discrete temporal windows, clocked by cycles of neural oscillations. An important testable prediction of this theory is that individuals' peak frequencies of oscillations should correlate with their ability to segregate the appearance of two successive stimuli. An influential study tested this prediction and showed that individual peak frequency of spontaneously occurring alpha (8-12 Hz) correlated with the temporal segregation threshold between two successive flashes of light [Samaha, J., & Postle, B. R. The speed of alpha-band oscillations predicts the temporal resolution of visual perception. Current Biology, 25, 2985-2990, 2015]. However, these findings were recently challenged [Buergers, S., & Noppeney, U. The role of alpha oscillations in temporal binding within and across the senses. Nature Human Behaviour, 6, 732-742, 2022]. To advance our understanding of the link between oscillations and temporal segregation, we devised a novel experimental approach. Rather than relying entirely on spontaneous brain dynamics, we presented a visual grating before the flash stimuli that is known to induce continuous oscillations in the gamma band (45-65 Hz). By manipulating the contrast of the grating, we found that high contrast induces a stronger gamma response and a shorter temporal segregation threshold, compared to low-contrast trials. In addition, we used a novel tool to characterize sustained oscillations and found that, for half of the participants, both the low- and high-contrast gratings were accompanied by a sustained and phase-locked alpha oscillation. These participants tended to have longer temporal segregation thresholds. Our results suggest that visual stimulus drive, reflected by oscillations in specific bands, is related to the temporal resolution of visual perception.

Neural signatures of evidence accumulation in temporal decisions.

Cognitive models of interval timing can be formulated as an accumulation-to-bound process.1-5 However, the physiological manifestation of such processes has not yet been identified. We used electroencephalography (EEG) to measure the neural responses of participants while they performed a temporal bisection task in which they were requested to categorize the duration of visual stimuli as short or long.6 We found that the stimulus-offset and response-locked activity depends on both stimulus duration and the participants' decision. To relate this activity to the underlying cognitive processes, we used a drift-diffusion model.7 The model includes a noisy accumulator starting with the stimulus onset and a decision threshold. According to the model, a stimulus duration will be categorized as "long" if the accumulator reaches the threshold during stimulus presentation. Otherwise, it will be categorized as "short." We found that at the offset of stimulus presentation, an EEG response marks the distance of the accumulator from the threshold. Therefore, this model offers an accurate description of our behavioral data as well as the EEG response using the same two model parameters. We then replicated this finding in an identical experiment conducted in the tactile domain. We also extended this finding to two different temporal ranges (sub- and supra-second). Taken together, the work provides a new way to study the cognitive processes underlying temporal decisions, using a combination of behavior, EEG, and modeling.

GABAB receptor deficiency causes failure of neuronal homeostasis in hippocampal networks.

Stabilization of neuronal activity by homeostatic control systems is fundamental for proper functioning of neural circuits. Failure in neuronal homeostasis has been hypothesized to underlie common pathophysiological mechanisms in a variety of brain disorders. However, the key molecules regulating homeostasis in central mammalian neural circuits remain obscure. Here, we show that selective inactivation of GABAB, but not GABA(A), receptors impairs firing rate homeostasis by disrupting synaptic homeostatic plasticity in hippocampal networks. Pharmacological GABA(B) receptor (GABA(B)R) blockade or genetic deletion of the GB(1a) receptor subunit disrupts homeostatic regulation of synaptic vesicle release. GABA(B)Rs mediate adaptive presynaptic enhancement to neuronal inactivity by two principle mechanisms: First, neuronal silencing promotes syntaxin-1 switch from a closed to an open conformation to accelerate soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly, and second, it boosts spike-evoked presynaptic calcium flux. In both cases, neuronal inactivity removes tonic block imposed by the presynaptic, GB(1a)-containing receptors on syntaxin-1 opening and calcium entry to enhance probability of vesicle fusion. We identified the GB(1a) intracellular domain essential for the presynaptic homeostatic response by tuning intermolecular interactions among the receptor, syntaxin-1, and the Ca(V)2.2 channel. The presynaptic adaptations were accompanied by scaling of excitatory quantal amplitude via the postsynaptic, GB(1b)-containing receptors. Thus, GABA(B)Rs sense chronic perturbations in GABA levels and transduce it to homeostatic changes in synaptic strength. Our results reveal a novel role for GABA(B)R as a key regulator of population firing stability and propose that disruption of homeostatic synaptic plasticity may underlie seizure's persistence in the absence of functional GABA(B)Rs.