bioRxiv Subject Collection: Neuroscience's Journal
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Saturday, May 25th, 2024
| Time |
Event |
| 1:31p |
Perceptual tri-stability, measured and fitted as emergent from a model for bistable alternations
The human auditory system in attempting to decipher ambiguous sounds appears to resort to perceptual exploration as evidenced by multi-stable perceptual alternations. This phenomenon has been widely investigated via the auditory streaming paradigm, employing ABA_ triplet sequences with much research focused on perceptual bi-stability with the alternate percepts as either a single integrated stream or as two simultaneous distinct streams. We extend this inquiry with experiments and modeling to include tri-stable perception. Here, the segregated percepts may involve a foreground/background distinction. We collected empirical data from participants engaged in a tri-stable auditory task, utilizing this dataset to refine a neural mechanistic model that had successfully reproduced multiple features of auditory bi-stability. Remarkably, the model successfully emulated basic statistical characteristics of tri-stability without substantial modification. This model also allows us to demonstrate a parsimonious approach to account for individual variability by adjusting the parameter of either the noise level or the neural adaptation strength. | | 1:31p |
Functional Heterogeneity of Voice-Encoding Cortex Revealed by Clinical Language Mapping
Regions in the superior temporal sulcus and gyrus have been heavily implicated in voice-selective responses in human auditory cortex. Despite an apparent specialization for the encoding of human voice, research outside the auditory domain suggests that these areas likely participate in additional neural processes including speech processing and production. The aim of the current study was to combine results of electrophysiological recording and clinical stimulation mapping procedures in patients undergoing stereoelectroencephalography (sEEG) to explore potential functional heterogeneity in voice-encoding cortex. Both channels that demonstrated voice-encoding properties and channels critically implicated in language functioning were heavily concentrated in the left STG/S. Analysis of functional overlap revealed channels in the posterior STG/S that appear to be involved in both voice encoding and language. Strength of voice encoding in these functionally diverse sites was not significantly different from sites that were implicated in voice encoding alone. Our findings add to prior observations of functional heterogeneity in the STG/S and contribute to proposed models of speech perception. We discuss these results in the context of the utility of electrophysiological methods in mapping cortical networks and identifying regions essential for functioning. | | 1:31p |
A synapse-specific refractory period for plasticity at individual dendritic spines
How newly formed memories are preserved while brain plasticity is ongoing has been a source of debate. One idea is that synapses which experienced recent plasticity become resistant to further plasticity, a type of metaplasticity often referred to as saturation. Here, we probe the local dendritic mechanisms that limit plasticity at recently potentiated synapses. We show that recently potentiated individual synapses exhibit a synapse-specific refractory period for further potentiation. We further found that the refractory period is associated with reduced postsynaptic CaMKII signaling; however, stronger synaptic activation only partially restored the ability for further plasticity. Importantly, the refractory period is released after one hour, a timing that coincides with the enrichment of several postsynaptic proteins to pre-plasticity levels. Notably, increasing the level of the postsynaptic scaffolding protein, PSD95, but not of PSD93, overcomes the refractory period. Our results support a model in which potentiation at a single synapse is sufficient to initiate a synapse-specific refractory period that persists until key postsynaptic proteins regain their steady-state synaptic levels. | | 1:31p |
Exploring the Architectural Biases of the Canonical Cortical Microcircuit
The cortex plays a crucial role in various perceptual and cognitive functions, driven by its basic unit, the canonical cortical microcircuit. Yet, we remain short of a framework that definitively explains the structure-function relationships of this fundamental neuroanatomical motif. To better understand how physical substrates of cortical circuitry facilitate their neuronal dynamics, we employ a computational approach using recurrent neural networks and representational analyses. We examine the differences manifested by the inclusion and exclusion of biologically-motivated inter-areal laminar connections on the computational roles of different neuronal populations in the microcircuit of two hierarchically-related areas, throughout learning. Our findings show that the presence of feedback connections correlates with the functional modularization of cortical populations in different layers, and provides the microcircuit with a natural inductive bias to differentiate expected and unexpected inputs at initialization. Furthermore, when testing the effects of training the microcircuit and its variants with a predictive-coding inspired strategy, we find that doing so helps better encode noisy stimuli in areas of the cortex that receive feedback, all of which combine to suggest evidence for a predictive coding mechanism serving as an intrinsic operative logic in the cortex. | | 1:31p |
The ARC Toolbox: Artificial Languages with Rhythmicity Control
Statistical learning is the ability to extract and retain statistical regularities from the environment. In language, extracting statistical regularities--so-called transitional probabilities, TPs--is crucial for segmenting speech and learning new words. To investigate whether neural activity synchronizes with these statistical patterns, so-called neural frequency-tagging paradigms have been employed. Here, brain activity is recorded while a stream of syllables is presented at one fixed rate (e.g., 3.3 Hz) and rhythmic patterns of low-TP events are present at a different rate (e.g., 1.1 Hz). Such studies report neural tracking of both syllables and TPs; that is, for both acoustic and abstract events, respectively. However, recent criticism pointed out that the possible confounding of acoustic and abstract rhythms limits the interpretability of this work. Here, we present a new Python toolbox that minimizes this confounding by creating Artificial languages with Rhythmicity Controls (ARC). ARC features a phonological rhythmicity index (PRI) to quantify the confounding periodicity of phonological features at the TP rate. It implements a pseudo-random-walk approach to ensure unconfounded TP stationarity throughout streams of arbitrary length. We provide a step-by-step guide to generate artificial pseudowords based on a pre-specified syllable inventory and create controlled lexicon streams. Simulation results show that ARC lexicons minimize PRI and TP variance, not only relative to sets of random syllable groups, but also to benchmarking sets of artificial languages used in the prior literature. ARC should be used by future work in order to suppress the confounding of acoustics and TPs in artificial language learning experiments. | | 1:31p |
Developmental maturation of frontal cortical circuits impacts decision-making
In humans, frontal cortical circuit maturation parallels the development of higher cognitive functions and is estimated to occur over the course of 15-20 years. In mice, frontal association cortex (FAC) maturation occurs over the first 6-8 weeks with limited reports on changes after sexual maturation (~7-8 weeks). Here we characterize frontal cortical circuits in mice across the first 6 months of life and uncovered cell-type and input-specific circuit refinement over this period, including a large increase in synaptic inhibition onto pyramidal cells relative to excitation. In parallel, we find age-related differences in the acquisition and execution of a FAC-dependent probabilistic 2-armed bandit task (2-ABT). Specifically, 4-6 month-old acquire the task more slowly and use different behavioral strategies to obtain rewards compared to younger mice. Lastly, we show that dampening the inhibitory activity in the FAC alters this behavior in a manner that counteracts the age-related differences. Together, these data present evidence for an extended period of structural synaptic maturation in FAC that directly impacts age-related changes in decision-making. | | 1:31p |
N-Methyl-D-aspartate receptor hypofunction causes recurrent and transient failures of perceptual inference
Perception alternates between an external mode, driven by sensory inputs, and an internal mode, shaped by prior knowledge. We found that the external mode is more prevalent during pharmacologically induced N-Methyl-D-aspartate receptor (NMDAR) hypofunction and in schizophrenia. This NMDAR-dependent increase in external mode suggests that psychotic experiences are caused by recurring dissociations of perception from prior knowledge about the world. | | 1:31p |
Dorsal striatum involvement in response conflict management - A lesion study in rats
Action control allows to respond to relevant stimuli while ignoring the non-relevant stimuli in the surrounding environment. In humans this process is generally studied in conflict tasks, such as the Simon task, in which participants respond with a left or right button press to the non-spatial relevant feature (e.g. the color) of a lateralized stimulus, while ignoring the stimulus position. In this study we used a visual version of the Simon task that we have previsously developed in rats to investigate the involvement of the dorsal striatum, a brain area that is central in action control processes. We tested the effect of excitotoxic lesions of the dorsomedial (DMS) and dorsolateral (DLS) areas in learning to control response interference. We showed that both DMS and DLS lesions negatively impacted rat performances, and this effect strongly depends on task practice. These results suggest an involvement of both areas in learning to manage response conflict. | | 2:46p |
Sex-focused analyses of M83 A53T hemizygous mouse model with recombinant human alpha-synuclein preformed fibril injection identifies female resilience to disease progression: A combined magnetic resonance imaging and behavioural study.
Alpha-synuclein (aSyn) pathology has been extensively studied in mouse models harbouring human mutations. In spite of the known sex differences in age of onset, prevalence and disease presentation in human synucleinopathies, the impact of sex on aSyn propagation has received very little attention. To address this need, we examined sex differences in whole brain signatures of neurodegeneration due to aSyn toxicity in the M83 mouse model using longitudinal magnetic resonance imaging (MRI; T1-weighted; 100 m3 isotropic voxel; acquired -7, 30, 90 and 120 days post-injection [dpi]; n[≥]8 mice/group/sex/time point). To initiate aSyn spreading, M83 mice were inoculated with recombinant human aSyn preformed fibrils (Hu-PFF) or phosphate buffered saline (PBS) injected in the right dorsal striatum. We observed more aggressive neurodegenerative profiles over time for male M83 Hu-PFF-injected mice when examining voxel-wise trajectories. However, at 90 dpi, we observed widespread patterns of neurodegeneration in the female Hu-PFF-injected mice. These differences were not accompanied with any differences in motor symptom onset between the male and female Hu-PFF-injected mice. However, male Hu-PFF-injected mice reached their humane endpoint sooner. These findings suggest that post-motor symptom onset, even though more accelerated disease trajectories were observed for male Hu-PFF-injected mice, neurodegeneration may appear sooner in female Hu-PFF-injected mice (prior to motor symptomatology). These findings suggest that sex-specific synucleinopathy phenotypes urgently need to be considered to improve our understanding of neuroprotective and neurodegenerative mechanisms. |
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