Object relations are processed with, but not without, awareness The scope of unconscious integration is widely debated. Here, we examined this question, focusing specifically on deciphering the relations between two associatively related objects, in a set of five behavioral and electrophysiological experiments. Participants were presented with masked pairs of related and unrelated objects and were asked to judge their relatedness. When the masked pairs were visible, we found both a behavioral priming effect and a difference in the magnitude of the electrophysiological N400 component for unrelated compared with related pairs. In sharp contrast, when the pairs were invisible (validated using both subjective and objective awareness measures), no convincing evidence was found for relatedness processing: with electroencephalography, no difference in N400 amplitude nor above-chance decoding of pair relations was found in two separate experiments. Based on these results, we conclude that the data do not support unconscious relatedness processing, suggesting that consciousness might have a prominent role in enabling relational integration beyond the single object level, which is in line with leading theories of consciousness.
Habenula contributions to negative self-cognitions Self-related cognitions are integral to personal identity and psychological wellbeing. Persistent engagement with negative self-cognitions can precipitate mental ill health; whereas the ability to restructure them is protective. Here, we leverage ultra-high field 7T fMRI and dynamic causal modelling to characterise a negative self-cognition network centred on the habenula – a small midbrain region linked to the encoding of punishment and negative outcomes. We model habenula effective connectivity in a discovery sample of healthy young adults (n = 45) and in a replication cohort (n = 56) using a cognitive restructuring task during which participants repeated or restructured negative self-cognitions. The restructuring of negative self-cognitions elicits an excitatory effect from the habenula to the posterior orbitofrontal cortex that is reliably observed across both samples. Furthermore, we identify an excitatory effect of the habenula on the posterior cingulate cortex during both the repeating and restructuring of self-cognitions. Our study provides evidence demonstrating the habenula’s contribution to processing self-cognitions. These findings yield unique insights into habenula’s function beyond processing external reward/punishment to include abstract internal experiences.
Evolving Engrams Demand Changes in Effective Cues A longstanding principle in episodic memory research, known as the encoding specificity hypothesis, holds that an effective retrieval cue should closely match the original encoding conditions. This principle assumes that a successful retrieval cue remains static over time. Despite the broad acceptance of this idea, it conflicts with one of the most well-established findings in memory research: The dynamic and ever-changing nature of episodic memories. In this article, we propose that the most effective retrieval cue should engage with the current state of the memory, which may have shifted significantly since encoding. By redefining the criteria for successful recall, we challenge a core principle of the field and open new avenues for exploring memory accessibility, offering fresh insights into both theoretical, and applied domains.
The neural basis of sharing information through goal-directed conversation: A hyperscanning functional magnetic resonance imaging study The human brain maintains internal models of physical and social environments, representing an individual’s “subjectivity”. Through conversation, two or more individuals share their models and modify them based on the exchange, a process that represents and is referred to as “intersubjectivity.” To investigate the neural substrates of this dynamic process, hyperscanning functional magnetic resonance imaging was conducted to test the hypothesis that Inter-Brain Synchronization (IBS) in the default mode network (DMN) is involved in representing intersubjectivity. Twenty-four Japanese-speaking participant pairs played maze games over a two-day period. Each participant pair received a different maze, i.e., a maze with a different pathway to its goal. Although pairs shared a maze, each participant in a pair had only partial knowledge of the maze layout and what they knew about the layout differed. Taking turns, participants moved their pieces to their goals. Since each had only partial information about the pathway, effective communication between partners was important. Behavioral data showed participants’ conversation about potential maze piece moves significantly increased as the game proceeded, implying that the exchange for such information was critical. Correspondingly, the DMN increased task-related activation, including the dorsomedial prefrontal cortex (dmPFC) and the bilateral temporoparietal junction (TPJ), extending through the superior temporal sulcus to the temporal pole and the right middle frontal gyrus. Within these areas, the dmPFC and the right TPJ showed task- and partner-specific IBS throughout all games. Thus, the DMN is likely required for representing intersubjectivity, based on internal models shared through real-time conversations.
Information, certainty, and learning More than four decades ago, Gibbon and Balsam (1981) showed that the acquisition of Pavlovian conditioning in pigeons is directly related to the informativeness of the conditioning stimulus (CS) about the unconditioned stimulus (US), where informativeness is defined as the ratio of the US-US interval (C) to the CS-US interval (T). However, the evidence for this relationship in other species has been equivocal. Here, we describe an experiment that measured the acquisition of appetitive Pavlovian conditioning in 14 groups of rats trained with different C/T ratios (ranging from 1.5 to 300) to establish how learning is related to informativeness. We show that the number of trials required for rats to start responding to the CS is determined by the C/T ratio and, remarkably, the specific scalar relationship between the rate of learning and informativeness aligns very closely to that previously obtained with pigeons. We also found that the response rate after extended conditioning is strongly related to T, with the terminal CS response rate being a scalar function of the CS reinforcement rate (1/T). Moreover, this same scalar relationship extended to the rats’ response rates during the (never-reinforced) inter-trial interval, which was directly proportional to the contextual rate of reinforcement (1/C). The findings establish that animals encode rates of reinforcement, and that conditioning is directly related to how much information the CS provides about the US. The consistency of the data across species, captured by a simple regression function, suggests a universal model of conditioning.
A top-down insular cortex circuit crucial for non-nociceptive fear learning Understanding how threats drive fear memory formation is crucial to understanding how organisms adapt to environments and treat threat-related disorders such as PTSD. While traditional Pavlovian conditioning studies have provided valuable insights, the exclusive reliance on electric shock as a threat stimulus has limited our understanding of diverse threats. To address this, we developed a conditioning paradigm using a looming visual stimulus as an unconditioned stimulus (US) in mice and identified a distinct neural circuit for visual threat conditioning. Parabrachial CGRP neurons were necessary for both conditioning and memory retrieval. Upstream neurons in the posterior insular cortex (pIC) responded to looming stimuli, and their projections to the parabrachial nucleus (PBN) induced aversive states and drove conditioning. However, this pIC-to-PBN pathway was not required for foot-shock conditioning. These findings reveal how non-nociceptive visual stimuli can drive aversive states and fear memory formation, expanding our understanding of aversive US processing beyond traditional models.
Brain connectome from neuronal morphology Single-subject morphological brain networks derived from cross-feature correlation of macroscopic MRI-derived morphological measures provide an important means for studying the brain connectome. However, the validity of this approach remains to be confirmed at the microscopic level. Here, we constructed morphological brain networks at the single-cell level by extending features from macroscopic morphological measures to microscopic descriptions of neuronal morphology. We demonstrated the feasibility and generalizability of the method using neurons in the somatosensory cortex of a rat, neurons over the whole brain of a mouse, and neurons in the middle temporal gyrus (MTG) of a human. We found that interneuron morphological similarity was higher for intra- than interclass connections, depended on cytoarchitectonic, chemoarchitectonic, and laminar classification of neurons (rat), differed between regions with different evolutionary timelines (mouse), and correlated with neuronal axonal projections (mouse). Furthermore, highly connected hub neurons were disproportionately from superficial layers (rat), inhibitory neurons (rat), and subcortical regions (mouse), and exhibited unique morphology. Finally, we demonstrated a more segregated, less integrated, and economic network architecture with worse resistance to targeted attacks for neurons in human MTG than neurons in a mouse’s primary visual cortex. Overall, our method provides an alternative avenue to study neuronal wiring diagrams in brains.
CXCL12 engages cortical inhibitory neurons to enhance dendritic spine plasticity and structured network activity The chemokine CXCL12 is a highly conserved peptide that regulates homeostatic processes in the brain throughout life. Recent work shows CXCL12 increases dendritic spine density in cortical neurons, which requires activation of CXCL12’s receptor CXCR4. This same pathway reverses cortical dendritic spine deficits and cognitive impairment in an animal model of neuroHIV. However, it remained unclear if CXCL12 simply preserved existing spines or also engaged spine plasticity processes that drove network-level adaptations. We therefore tested if CXCL12 could regulate dendritic spine turnover, maturation, clustering, and neuronal network activity in primary rat cortical neurons of either sex using live-cell imaging, confocal microscopy, and multi-electrode arrays. Intriguingly, CXCL12-treated neurons formed significantly more new spines than controls, and this outcome was blocked by the CXCR4 antagonist AMD3100. CXCL12 also increased the density of thin spines expressing post-synaptic markers, including postsynaptic density protein 95 (PSD-95), phospho-PSD-95Ser295 and GluA1, and allowed neurons to better maintain synaptic PSD-95 puncta size. Thin spines were modestly closer together after CXCL12 treatment, suggesting a possible effect on anatomical spine clustering. These effects translated to structured network activity, as CXCL12 increased spike frequency within network bursts in multi-electrode array cultures. Finally, a targeted knockdown of CXCR4 in inhibitory neurons, which mostly lack dendritic spines, prevented CXCL12 from increasing spine density on excitatory neurons. Overall, our findings suggest CXCL12/CXCR4 signaling engages inhibitory neurons along with multiple aspects of spine dynamics and remodeling to shape how broader neuronal networks function.