bioRxiv Science⌕ Search

bioRxiv · 10.1101/2020.05.19.103572

Did I imagine that? The functional role of paracingulate cortex in reality monitoring

Abstract

Reality monitoring describes our ability to distinguish between internally and externally generated experiences. Individuals show significant variation in this ability and impaired reality monitoring has been linked to the experience of hallucinations. We undertook two studies to investigate the association between reality monitoring and morphology of the paracingulate region of medial prefrontal cortex. In Study 1 we compared reality monitoring accuracy and functional connectivity within paracingulate cortex in groups of healthy controls (N=20) and patients with schizophrenia and hallucinations (N=19). Controls showed greater reality monitoring accuracy that was associated with resting-state functional connectivity between paracingulate, precuneus and occipital cortices, while reality monitoring in patients was associated with more lateral functional connectivity. In Study 2 we used real-time fMRI neurofeedback to obtain causal evidence for the role of the paracingulate cortex in reality monitoring. Healthy individuals received Active feedback from paracingulate cortex (N=21) or Sham feedback based on randomised signal (N=18). Active-group participants showed a specific behavioural effect of improved reality monitoring for Imagined items, as well as increases in both activity within the paracingulate region, and its posterior functional connectivity with precuneus and lateral parietal cortices, and occipital cortex. Our findings suggest reality monitoring in healthy individuals is causally supported by a paracingulate mediated flexible network including the precuneus. Network connectivity can be enhanced using neurofeedback and tracks with improved reality monitoring ability. In contrast, patients with schizophrenia may utilise a distinct and more lateral network which may explain observed sub-optimal reality monitoring accuracy, contributing to the experience of hallucinations. Significance StatementReality monitoring refers to our ability to distinguish imagination from our experiences in the outside world, and is linked both to hallucinations in schizophrenia as well as to the morphology of paracingulate cortex area of the brain. Here, we revealed less paracingulate involvement in the functional reality monitoring networks in patients with schizophrenia compared to healthy individuals. Thereafter, we used real-time fMRI neurofeedback to show that healthy individuals can learn to upregulate brain activity within the paracingulate cortex, with this resulting in both improved reality monitoring ability and changes in paracingulate functional connectivity. This suggests that paracingulate cortex activity and connectivity play a causal role in reality monitoring, with implications for both the understanding and treatment of hallucinations.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Garrison, J. R., Saviola, F., Morgenroth, E., Barker, H., Luhrs, M., Simons, J., Fernyhough, C. P., Allen, P.. 2020-05-21. Did I imagine that? The functional role of paracingulate cortex in reality monitoring. https://doi.org/10.1101/2020.05.19.103572

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Epidermal Langerhans Cells Act as Neuroimmune Regulators of Pain and Itch

Neuroimmune interactions in the skin coordinate immune defense and somatosensory perception, yet how immune cells shape sensory signaling remains poorly defined. Here, we show that Langerhans cells (LCs), epidermal antigen-presenting cells, function as local immune-derived amplifiers of cutaneous sensory signaling. Anatomical and transcriptomic analyses reveal preferential LC association with non-peptidergic sensory neurons. LC activation increases neuronal and behavioral responses to thermal, mechanical, and pruritic stimuli without directly exciting sensory neurons, whereas LC inhibition or ablation selectively reduces pruritogen-evoked itch. We identified semaphorin 7A as a candidate LC-expressed mediator. Semaphorin 7A sensitized cultured sensory neurons to chloroquine and histamine, and neutralizing semaphorin 7A abolished the increase in chloroquine-evoked scratching produced by LC activation. Its receptor PlexinC1 was expressed by most MrgprA3 pruriceptors and blocking PlexinC1 reduced semaphorin 7A-evoked neuronal responses. Together, these findings identify epidermal LCs as local immune-derived amplifiers that regulate the responsiveness of cutaneous sensory circuits and identify semaphorin 7A as a mediator of LC-induced itch potentiation.

neuroscience↗

Feasible closed-loop stimulation for neural latent dynamics control

Modern neuroscience benefits from powerful computational and experimental methods for studying neural populations, including latent dynamics models that predict behavior with few dimensions. But despite their explanatory utility, latent factors are seldom targeted explicitly with experimental perturbations, leaving causal relationships to behavior and inferred dynamical landscapes untested. A promising solution is closed-loop, multi-channel optogenetic control, which, when paired with model predictions, could steer neural trajectories in real time--a feat impossible for traditional, hand-designed stimulation. However, because closed-loop latent control has not been demonstrated in vivo, the hardware and software requirements remain unclear--particularly the necessary stimulation dimensionality and how limited resources such as implant volume and bandwidth should be allocated between stimulation and recording capabilities. Preliminary experiments would thus help guide ongoing technological development. As large-scale exploration of these design spaces in vivo is prohibitively expensive, we conducted a high-throughput simulation survey using biophysically grounded spiking neural networks. We found that low-dimensional actuation is sufficient: in the reference configuration, ~20% of the stimulation channels achieved ~85% of peak control performance, far fewer than the number of neurons. Furthermore, allocating channels roughly equally between stimulation and recording optimized behavioral control, whereas pairing many electrodes with a single light source--the prevailing practice in experimental labs--performed poorly. Even without heavily optimizing modeling or control, we obtained >60% tracking error reduction and >90% evoked behavior accuracy on average for optimal channel counts. These results held across extensive parameter variations, suggesting that closed-loop latent control is feasible with accessible channel counts and establishing design principles for future tool development and in vivo experiments.

neuroscience↗

Identification of Kinome Biomarkers and Therapeutic Rescue in cGMP-Linked Retinal Degeneration

Inherited retinal degenerations, such as Retinitis Pigmentosa (RP) and Leber's congenital amaurosis (LCA), are major causes of progressive and irreversible vision loss. The large number of genes associated with these disorders makes their clinical and molecular characterization difficult, while systemic biomarkers for disease progression or treatment response remain limited. These challenges were addressed by targeting cGMP-associated mechanisms shared by RP and LCA and integrating systemic biomarker profiling with retinal outcomes. Kinase activity analysis (kinome analysis) in peripheral blood mononuclear cells distinguished healthy and diseased states and captured therapy-associated signatures in rd10 mice treated with LP-CN03, a liposomal formulation of the cGMP analog CN03. This first systemic analysis in a therapeutically responsive animal model highlights kinome analysis as a potential translational readout. Given shared cGMP signaling in RP and AIPL1-associated LCA, LP-CN03's therapeutic potential was further evaluated in a new CRISPR-Cas9-generated Aipl1-/- mouse model. Treatment with LP-CN03 preserved retinal structure and function, as shown by electroretinography, longitudinal optical coherence tomography, fundus imaging, optomotor testing, and photoreceptor-specific gene expression. Together, these findings provide independent in vivo evidence for the neuroprotective effect of LP-CN03 in both cGMP-related RP and LCA, also highlighting the translational value of kinome profiling.

neuroscience↗