Human Anterior Insula Encodes Performance Feedback and Relays Prediction Error to the Medial Prefrontal Cortex

Abstract Adaptive behavior requires the comparison of outcome predictions with actual outcomes (e.g., performance feedback). This process of performance monitoring is computed by a distributed brain network comprising the medial prefrontal cortex (mPFC) and the anterior insular cortex (AIC). Despite being consistently co-activated during different tasks, the precise neuronal computations of each region and their interactions remain elusive. In order to assess the neural mechanism by which the AIC processes performance feedback, we recorded AIC electrophysiological activity in humans. We found that the AIC beta oscillations amplitude is modulated by the probability of performance feedback valence (positive or negative) given the context (task and condition difficulty). Furthermore, the valence of feedback was encoded by delta waves phase-modulating the power of beta oscillations. Finally, connectivity and causal analysis showed that beta oscillations relay feedback information signals to the mPFC. These results reveal that structured oscillatory activity in the anterior insula encodes performance feedback information, thus coordinating brain circuits related to reward-based learning.

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Modality-specific effects of aversive expectancy in the anterior insula and medial prefrontal cortex

Pain ◽

10.1097/j.pain.0000000000001237 ◽

2018 ◽

Vol 159 (8) ◽

pp. 1529-1542 ◽

Cited By ~ 8

Author(s):

Gil Sharvit ◽

Corrado Corradi-DellʼAcqua ◽

Patrik Vuilleumier

Keyword(s):

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Anterior Insula ◽

Specific Effects

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Being asked to tell an unpleasant truth about another person activates anterior insula and medial prefrontal cortex

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2015.00553 ◽

2015 ◽

Vol 9 ◽

Cited By ~ 4

Author(s):

Melissa M. Littlefield ◽

Martin J. Dietz ◽

Des Fitzgerald ◽

Kasper J. Knudsen ◽

James Tonks

Keyword(s):

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Anterior Insula

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Oscillatory Activity in the Medial Prefrontal Cortex and Nucleus Accumbens Correlates with Impulsivity and Reward Outcome

PLoS ONE ◽

10.1371/journal.pone.0111300 ◽

2014 ◽

Vol 9 (10) ◽

pp. e111300 ◽

Cited By ~ 33

Author(s):

Nicholas A. Donnelly ◽

Tahl Holtzman ◽

P. Dylan Rich ◽

Alejo J. Nevado-Holgado ◽

Anushka B. P. Fernando ◽

...

Keyword(s):

Prefrontal Cortex ◽

Nucleus Accumbens ◽

Medial Prefrontal Cortex ◽

Oscillatory Activity

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Equality versus self-interest in the brain: Differential roles of anterior insula and medial prefrontal cortex

NeuroImage ◽

10.1016/j.neuroimage.2012.04.037 ◽

2012 ◽

Vol 62 (1) ◽

pp. 102-112 ◽

Cited By ~ 74

Author(s):

Claudia Civai ◽

Cristiano Crescentini ◽

Aldo Rustichini ◽

Raffaella Ida Rumiati

Keyword(s):

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Anterior Insula ◽

Self Interest ◽

The Brain

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Context-invariant neural dynamics underlying the encoding of Bayesian uncertainty, but not confidence

10.1101/794669 ◽

2019 ◽

Author(s):

Vincenzo G. Fiore ◽

Xiaosi Gu

Keyword(s):

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Effective Connectivity ◽

Sensory Information ◽

Anterior Insula ◽

Anterior Cingulate ◽

Neural Dynamics ◽

Network Computing ◽

Evidence Accumulation ◽

Healthy Humans

AbstractBeliefs about action-outcomes contingencies are often updated in opaque environments where feedbacks might be inaccessible and agents might need to rely on other information for evidence accumulation. It remains unclear, however, whether and how the neural dynamics subserving confidence and uncertainty during belief updating might be context-dependent. Here, we applied a Bayesian model to estimate uncertainty and confidence in healthy humans (n=28) using two multi-option fMRI tasks, one with and one without feedbacks. We found that across both tasks, uncertainty was computed in the anterior insular, anterior cingulate, and dorsolateral prefrontal cortices, whereas confidence was encoded in anterior hippocampus, amygdala and medial prefrontal cortex. However, dynamic causal modelling (DCM) revealed a critical divergence between how effective connectivity in these networks was modulated by the available information. Specifically, there was directional influence from the anterior insula to other regions during uncertainty encoding, independent of outcome availability. Conversely, the network computing confidence was driven either by the anterior hippocampus when outcomes were not available, or by the medial prefrontal cortex and amygdala when feedbacks were immediately accessible. These findings indicate that confidence encoding might largely rely on evidence accumulation and therefore dynamically changes as a function of the available sensory information (i.e. symbolic sequences monitored by the hippocampus, and monetary feedbacks computed by amygdala and medial prefrontal cortex). In contrast, uncertainty could be triggered by any information that disputes existing beliefs (i.e. processed in the insula), independent of its content.Significance StatementOur choices are guided by our beliefs about action-outcome contingencies. In environments where only one action leads to a desired outcome, high estimated action-outcome probabilities result in confidence, whereas low probabilities distributed across multiple choices result in uncertainty. These estimations are continuously updated, sometimes based on feedbacks provided by the environment, but sometimes this update takes place in opaque environments where feedbacks are not readily available. Here, we show that uncertainty computations are driven by the anterior insula, independent of feedback availability. Conversely, confidence encoding dynamically adapts to the information available, as we found it was driven either by the anterior hippocampus, when feedback was absent, or by the medial prefrontal cortex and amygdala, otherwise.

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Insula to mPFC reciprocal connectivity differentially underlies novel taste neophobic response and learning

10.1101/2021.07.05.451133 ◽

2021 ◽

Author(s):

Haneen Kayyal ◽

Sailendrakumar Kolatt Chandran ◽

Adonis Yiannakas ◽

Nathaniel Gould ◽

Mohammad Khamaisy ◽

...

Keyword(s):

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Sensory Information ◽

Insular Cortex ◽

Memory Formation ◽

Intrinsic Properties ◽

Insight Into ◽

Taste Experience ◽

Neophobic Response

To survive in an ever-changing environment, animals must detect and learn salient information. The anterior insular cortex (aIC) and medial prefrontal cortex (mPFC) are heavily implicated in salience and novelty processing, and specifically, the processing of taste sensory information. Here, we examined the role of aIC-mPFC reciprocal connectivity in novel taste neophobia and memory formation, in mice. Using pERK and neuronal intrinsic properties as markers for neuronal activation, and retrograde AAV (rAAV) constructs for connectivity, we demonstrate a correlation between aIC-mPFC activity and novel taste experience. Furthermore, by expressing inhibitory chemogenetic receptors in these projections, we show that aIC-to-mPFC activity is necessary for both taste neophobia and its attenuation. However, activity within mPFC-to-aIC projections is essential only for the neophobic reaction but not for the learning process. These results provide an insight into the cortical circuitry needed to detect, react to- and learn salient stimuli, a process critically involved in psychiatric disorders.

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Basolateral Amygdala but Not Medial Prefrontal Cortex Contributes to Chronic Fluoxetine Treatments for PTSD Symptoms in Mice

Behavioural Neurology ◽

10.1155/2020/8875087 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Ying Hao Yu ◽

Chen Yin Ou ◽

Bai Chuang Shyu ◽

Andrew Chih Wei Huang

Keyword(s):

Prefrontal Cortex ◽

Fear Conditioning ◽

Medial Prefrontal Cortex ◽

Basolateral Amygdala ◽

Neural Mechanism ◽

Ptsd Symptoms ◽

Comorbid Depression ◽

Chronic Fluoxetine ◽

Swimming Test ◽

Fos Expression

Do chronic fluoxetine treatments reduced footshock-induced posttraumatic stress disorder (PTSD) symptoms, including fear and comorbid depression, in the situational reminder phase? Moreover, are the subareas of the medial prefrontal cortex (mPFC), including the cingulate cortex 1 (Cg1), prelimbic cortex (PrL), infralimbic cortex (IL), and basolateral amygdala (BLA), involved in the fluoxetine amelioration of PTSD symptoms? These two crucial issues were addressed in the present study. All mice were injected with chronic fluoxetine or normal saline treatments for the adaptation (14 days), footshock fear conditioning (1 day), and situational reminder (3 days) phases. After adaptation, the mice were subjected to footshock (2 mA, 10 seconds) or nonfootshock and stayed 2 min in a footshock box for 2 min for fear conditioning. Later, they were placed in the footshock box for 2 min in the situational reminder phase. In the final session of the situational reminder phase, a forced swimming test (FST) and immunohistochemical staining were conducted. The results indicated that footshock induced fear and comorbid depression. Meanwhile, chronic fluoxetine treatments reduced fear and depression behaviors. The Cg1, PrL, IL, and BLA were seemingly to increase c-Fos expression after footshock-induced PTSD symptoms in the situational reminder phase. The fluoxetine treatments reduced only the BLA’s c-Fos expression. The findings suggest that BLA contributes to the fluoxetine amelioration of PTSD symptoms; however, the mPFC, including the Cg1, PrL, and IL, did not mediate PTSD symptoms’ amelioration stemming from fluoxetine. The present data might help us to further understand the neural mechanism of fluoxetine treatments in PTSD symptoms.

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Early memory deficits and extensive brain network disorganization in the AppNL-F/MAPT double knock-in mouse model of familial Alzheimer's disease.

10.1101/2021.04.11.439177 ◽

2021 ◽

Author(s):

Christopher Borcuk ◽

Celine Heraud ◽

Karine Herbeaux ◽

Margot Diringer ◽

Elodie Panzer ◽

...

Keyword(s):

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Information Flow ◽

Medial Temporal Lobe ◽

Disease Onset ◽

Memory Loss ◽

Brain Network ◽

Retrosplenial Cortex ◽

Network Efficiency ◽

The Relationship

A critical challenge in current research on AD is to clarify the relationship between early neuropathology and network dysfunction associated to the emergence of subtle memory alterations which announce disease onset. In the present work, the new generation AppNL-F/MAPT double knock in (dKI) model was used to evaluate early stages of AD. The initial step of tau pathology was restricted to the perirhinal-entorhinal region, sparing the hippocampus. This discrete neuropathological sign was associated with deficits in the object-place associative memory, one of the earliest recognition memories affected in individuals at risk for developing AD. Analyses of task-dependent c-Fos activation was carried out in 22 brain regions across the medial prefrontal cortex, claustrum, retrosplenial cortex, and medial temporal lobe. Initial hyperactivity was detected in the entorhinal cortex and the claustrum of dKI mice. The retention phase was associated to reduced network efficiency especially across cingulate cortical regions, which may be caused by a disruption of information flow through the retrosplenial cortex. Moreover, the relationship between network global efficiency and memory performance in the WT could predict memory loss in the dKI, further linking reduced network efficiency to memory dysfunction. Our results suggest that early perirhinal-entorhinal pathology is associated with local hyperactivity which spreads towards connected regions such as the claustrum, the medial prefrontal cortex and ultimately the key retrosplenial hub which is needed to relay information flow from frontal to temporal lobes. The similarity between our findings and those reported in the earliest stages of AD suggests that the AppNL-F/MAPT dKI model has a high potential for generating key information on the initial stage of the disease.

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Insula to mPFC reciprocal connectivity differentially underlies novel taste neophobic response and learning

eLife ◽

10.7554/elife.66686 ◽

2021 ◽

Vol 10 ◽

Author(s):

Haneen Kayyal ◽

Sailendrakumar Kolatt Chandran ◽

Adonis Yiannakas ◽

Nathaniel Gould ◽

Mohammad Khamaisy ◽

...

Keyword(s):

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Sensory Information ◽

Insular Cortex ◽

Memory Formation ◽

Intrinsic Properties ◽

Insight Into ◽

Taste Experience ◽

Neophobic Response

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Metabolic Brain Network Analysis With 18F-FDG PET in a Rat Model of Neuropathic Pain

Frontiers in Neurology ◽

10.3389/fneur.2021.566119 ◽

2021 ◽

Vol 12 ◽

Author(s):

Bei-Bei Huo ◽

Mou-Xiong Zheng ◽

Xu-Yun Hua ◽

Jun Shen ◽

Jia-Jia Wu ◽

...

Keyword(s):

Neuropathic Pain ◽

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Entorhinal Cortex ◽

Brain Regions ◽

Brain Network ◽

Caudate Putamen ◽

Metabolic Connectivity ◽

Network Properties ◽

The Brain

Neuropathic pain has been found to be related to profound reorganization in the function and structure of the brain. We previously demonstrated changes in local brain activity and functional/metabolic connectivity among selected brain regions by using neuroimaging methods. The present study further investigated large-scale metabolic brain network changes in 32 Sprague–Dawley rats with right brachial plexus avulsion injury (BPAI). Graph theory was applied in the analysis of 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) PET images. Inter-subject metabolic networks were constructed by calculating correlation coefficients. Global and nodal network properties were calculated and comparisons between pre- and post-BPAI (7 days) status were conducted. The global network properties (including global efficiency, local efficiency and small-world index) and nodal betweenness centrality did not significantly change for all selected sparsity thresholds following BPAI (p > 0.05). As for nodal network properties, both nodal degree and nodal efficiency measures significantly increased in the left caudate putamen, left medial prefrontal cortex, and right caudate putamen (p < 0.001). The right entorhinal cortex showed a different nodal degree (p < 0.05) but not nodal efficiency. These four regions were selected for seed-based metabolic connectivity analysis. Strengthened connectivity was found among these seeds and distributed brain regions including sensorimotor area, cognitive area, and limbic system, etc. (p < 0.05). Our results indicated that the brain had the resilience to compensate for BPAI-induced neuropathic pain. However, the importance of bilateral caudate putamen, left medial prefrontal cortex, and right entorhinal cortex in the network was strengthened, as well as most of their connections with distributed brain regions.

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