Altered hierarchical auditory predictive processing after lesions to the orbitofrontal cortex
- University of Oslo, Norway
- University of California, Berkeley, United States
- Oslo University Hospital, Norway
- Rigshospitalet, Norway
Abstract
Orbitofrontal cortex (OFC) is classically linked to inhibitory control, emotion regulation and reward processing. Recent perspectives propose that the OFC also generates predictions about perceptual events, actions, and their outcomes. We tested the role of the OFC in detecting violations of prediction at two levels of abstraction (i.e., hierarchical predictive processing) by studying the event-related potentials (ERPs) of patients with focal OFC lesions (n = 12) and healthy controls (n = 14) while they detected deviant sequences of tones in a Local-Global paradigm. The structural regularities of the tones were controlled at two hierarchical levels by rules defined at a local (i.e., between tones within sequences) and at a global (i.e., between sequences) level. In OFC patients, ERPs elicited by standard tones were unaffected at both local and global levels compared to controls. However, patients showed an attenuated mismatch negativity (MMN) and P3a to local prediction violation, as well as a diminished MMN followed by a delayed P3a to the combined local and global level prediction violation. The subsequent P3b component to conditions involving violations of prediction at the level of global rules was preserved in the OFC group. Comparable effects were absent in patients with lesions restricted to the lateral PFC, which lends a degree of anatomical specificity to the altered predictive processing resulting from OFC lesion. Overall, the altered magnitudes and time courses of MMN/P3a responses after lesions to the OFC indicate that the neural correlates of detection of auditory regularity violation is impacted at two hierarchical levels of rule abstraction.
Data availability
We do not have permission from the Regional Committees for Medical and Health Research Ethics (REC) to share clinical data publicly. The conditions of the ethical approval of this study do not permit public archiving of de-identified data. Neither the patients nor the healthy control participants have consented to making their data publicly available. The reasons for the restrictions concerning public sharing of clinical data is that the patient samples are small given the relative rareness of individuals with focal brain lesions, and thus the constellation of demographic and clinical information results in an increased risk of patients being identified.Interested researchers seeking access to the original de-identified data supporting the claims in this paper would have to submit a short study plan of the proposed research to the PI of the project and lesion registry, Anne-Kristin Solbakk (a.k.solbakk@psykologi.uio.no). The study plan would be evaluated by the project PI, the head of the Department of Neurosurgery at Oslo University Hospital, and the head of research at the Department of Psychology. Next, the PI would ask REC for permission to share de-identified data with the researcher/institution. After REC approval, the head of research at the Department of Psychology, the Data Protection Officer at Oslo University Hospital, and the other interested party would sign data transfer agreements, before data transfer would take place. The data can be accessed and used only for academic purposes. Commercial research cannot be performed on the data.Materials for the Experimental scripts and task stimuli, custom analysis code, and a processed version of the dataset are available at https://osf.io/f9m76/
Article and author information
Author details
Alejandro Omar Blenkmann
Funding
Research Council of Norway (240389)
- Torstein R Meling
- Tor Endestad
- Anne-Kristin Solbakk
Research Council of Norway (314925)
- Alejandro Omar Blenkmann
Research Council of Norway (RITMO 262762)
- Tor Endestad
- Anne-Kristin Solbakk
Research Council of Norway (RITPART 274996)
- Tor Endestad
- Anne-Kristin Solbakk
National Institute of Neurological Disorders and Stroke (NINDS R37NS21135)
- Robert T Knight
National Institute of Neurological Disorders and Stroke (Conte Center PO 518 MH109429)
- Robert T Knight
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Ethics Statement:The study involving human participants was reviewed and approved by Regional Committees for Medical and Health Research Ethics, South-East Norway (REK ref. number: 2014/381) as part of a larger study. The study was conducted in accordance with the principles stated in the Declaration of Helsinki. All participants provided written informed consent and received compensation for their participation.
Copyright
© 2024, Asko et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 784
- views
-
- 117
- downloads
-
- 0
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Altered hierarchical auditory predictive processing after lesions to the orbitofrontal cortex
eLife 13:e86386.
https://doi.org/10.7554/eLife.86386
Further reading
-
- Developmental Biology
- Neuroscience
Environmental insults, including mild head trauma, significantly increase the risk of neurodegeneration. However, it remains challenging to establish a causative connection between early-life exposure to mild head trauma and late-life emergence of neurodegenerative deficits, nor do we know how sex and age compound the outcome. Using a Drosophila model, we demonstrate that exposure to mild head trauma causes neurodegenerative conditions that emerge late in life and disproportionately affect females. Increasing age-at-injury further exacerbates this effect in a sexually dimorphic manner. We further identify sex peptide signaling as a key factor in female susceptibility to post-injury brain deficits. RNA sequencing highlights a reduction in innate immune defense transcripts specifically in mated females during late life. Our findings establish a causal relationship between early head trauma and late-life neurodegeneration, emphasizing sex differences in injury response and the impact of age-at-injury. Finally, our findings reveal that reproductive signaling adversely impacts female response to mild head insults and elevates vulnerability to late-life neurodegeneration.
-
- Neuroscience
Neurotensin (Nts) is a neuropeptide acting as a neuromodulator in the brain. Pharmacological studies have identified Nts as a potent hypothermic agent. The medial preoptic area, a region that plays an important role in the control of thermoregulation, contains a high density of neurotensinergic neurons and Nts receptors. The conditions in which neurotensinergic neurons play a role in thermoregulation are not known. In this study, optogenetic stimulation of preoptic Nts neurons induced a small hyperthermia. In vitro, optogenetic stimulation of preoptic Nts neurons resulted in synaptic release of GABA and net inhibition of the preoptic pituitary adenylate cyclase-activating polypeptide (Adcyap1) neurons firing activity. GABA-A receptor antagonist or genetic deletion of Slc32a1 (VGAT) in Nts neurons unmasked also an excitatory effect that was blocked by a Nts receptor 1 antagonist. Stimulation of preoptic Nts neurons lacking Slc32a1 resulted in excitation of Adcyap1 neurons and hypothermia. Mice lacking Slc32a1 expression in Nts neurons presented changes in the fever response and in the responses to heat or cold exposure as well as an altered circadian rhythm of body temperature. Chemogenetic activation of all Nts neurons in the brain induced a 4–5°C hypothermia, which could be blocked by Nts receptor antagonists in the preoptic area. Chemogenetic activation of preoptic neurotensinergic projections resulted in robust excitation of preoptic Adcyap1 neurons. Taken together, our data demonstrate that endogenously released Nts can induce potent hypothermia and that excitation of preoptic Adcyap1 neurons is the cellular mechanism that triggers this response.
