Project Title
Neurobiological mechanisms of uncertainty processing and its relationship with anxiety symptoms in healthy individuals and patients with obsessive- compulsive disorder
Partner Organisations
Internal ID
1251073
Principal Investigator
Type
basic research
Status
VIGENTE
Start Date
April 1, 2025
End Date
April 1, 2029
Investigators
Valero-cabre Antoni
Description
Managing uncertainty is crucial for adaptive behavior in a constantly changing world. In such a context,
uncertainty refers to situations with low predictability of environmental events and the consequences of our
actions. Understanding how the brain estimates and manages uncertainty is vital for daily life. The ability to
handle uncertainty is linked to various psychological and neuropsychiatric disorders, including anxiety and
obsessive-compulsive disorder (OCD). Growing evidence indicated that anxiety impacts decision-making in
uncertain environments. Two key aspects of anxiety include heightened anticipation of aversive events and
anticipatory representations of possible uncertain future events. Anxiety symptoms are relevant across
different disorders, making their neurobiological understanding essential for therapeutic strategies. Although
anxiety is prevalent in various mental health disorders, it is also crucial for understanding OCD. This disorder
is characterized by obsessions and compulsions aimed at reducing anxiety. Patients with OCD show
impairments in decision-making under ambiguity, intolerance to uncertainty, and increased anxiety.
Neurobiological alterations in OCD include hyperactivity in the Cortico-Striato-Thalamo-Cortical (CSTC)
circuit and increased amygdala activity. Recent studies suggest that the neurological mechanisms linking
anxiety and uncertainty are key to certain OCD aspects. Compulsive behaviors in OCD may stem from the
brain's disrupted ability to manage uncertainty, especially in novel, goal-oriented contexts.
This research project aims to investigate the cognitive and neurobiological mechanisms underlying decisionmaking under uncertainty and their relationship with anxiety symptoms in healthy individuals and patients
with OCD. The study proposes three pathways that link uncertainty processing to anxiety, as follows.
• Uncertainty Aversion: the preference for known risks over unknown risks. It is linked to the Amygdala
Cingular-Insular network activity, anxiety symptoms, and perceiving and avoiding environmental threats.
• Uncertainty Management: how people manage high uncertainty when avoidance is impossible,
involving fronto-parietal networks and attentional biases. Although it represents less studying processing,
it is thought that it is related to anxiety by increasing attention to uncertainty threats.
• Learning Under Uncertainty: adjusting learning strategies in response to environmental uncertainty,
involving prediction errors estimations and exploratory behaviors. Evidence indicated an alteration in such
processing in healthy individuals with anxiety traits and patients with OCD linked to front-striatal value
network alterations.
The project hypothesizes that the degree to which uncertainty modulates decision-making and learning
correlates with anxiety traits, mediated by specific cognitive computations and activity in different brain
networks in both healthy individuals and OCD patients.
We propose an experimental design involving two decision-making tasks under uncertainty (Ambiguity
Attitude-Management task and Learning under Uncertainty task), neuroimaging techniques (fMRI and DTI),
non-invasive brain stimulation (TMS), and EEG to explore the proposed neuronal and cognitive pathways.
Additionally, the study will involve two participant groups: healthy controls and patients with OCD to test our
hypothesis. This approach aims to explore cognitive and neuronal mechanisms linking uncertainty to anxiety
and to establish whether these pathways represent mediated processing of uncertainty and anxiety,
understanding anxiety as a transdiagnostic symptom.
Our cognitive tasks aim to distinguish between Uncertainty Aversion, Uncertainty Management, and Learning
Under Uncertainty. Functional MRI, EEG, TMS, and computational cognitive modeling will be employed to
study brain activity in three different networks, testing their causal mechanisms in processing uncertainty.
Exploring the consistency in the relationship between the proposed neuronal representation and anxiety in
both healthy individuals and patients with OCD will provide insights into the transdiagnostic mechanisms of
anxiety. Additionally, Comparing OCD patients and healthy controls will shed light on the specific mechanisms
underlying decision-making impairments in OCD.
This project aims to provide causal evidence of how different brain networks contribute to decision-making
under uncertainty and its link with anxiety in healthy individuals and OCD patients. The findings could inform
the development of targeted, non-invasive brain stimulation therapies for anxiety, enhancing mental health
treatment and patient outcomes.
uncertainty refers to situations with low predictability of environmental events and the consequences of our
actions. Understanding how the brain estimates and manages uncertainty is vital for daily life. The ability to
handle uncertainty is linked to various psychological and neuropsychiatric disorders, including anxiety and
obsessive-compulsive disorder (OCD). Growing evidence indicated that anxiety impacts decision-making in
uncertain environments. Two key aspects of anxiety include heightened anticipation of aversive events and
anticipatory representations of possible uncertain future events. Anxiety symptoms are relevant across
different disorders, making their neurobiological understanding essential for therapeutic strategies. Although
anxiety is prevalent in various mental health disorders, it is also crucial for understanding OCD. This disorder
is characterized by obsessions and compulsions aimed at reducing anxiety. Patients with OCD show
impairments in decision-making under ambiguity, intolerance to uncertainty, and increased anxiety.
Neurobiological alterations in OCD include hyperactivity in the Cortico-Striato-Thalamo-Cortical (CSTC)
circuit and increased amygdala activity. Recent studies suggest that the neurological mechanisms linking
anxiety and uncertainty are key to certain OCD aspects. Compulsive behaviors in OCD may stem from the
brain's disrupted ability to manage uncertainty, especially in novel, goal-oriented contexts.
This research project aims to investigate the cognitive and neurobiological mechanisms underlying decisionmaking under uncertainty and their relationship with anxiety symptoms in healthy individuals and patients
with OCD. The study proposes three pathways that link uncertainty processing to anxiety, as follows.
• Uncertainty Aversion: the preference for known risks over unknown risks. It is linked to the Amygdala
Cingular-Insular network activity, anxiety symptoms, and perceiving and avoiding environmental threats.
• Uncertainty Management: how people manage high uncertainty when avoidance is impossible,
involving fronto-parietal networks and attentional biases. Although it represents less studying processing,
it is thought that it is related to anxiety by increasing attention to uncertainty threats.
• Learning Under Uncertainty: adjusting learning strategies in response to environmental uncertainty,
involving prediction errors estimations and exploratory behaviors. Evidence indicated an alteration in such
processing in healthy individuals with anxiety traits and patients with OCD linked to front-striatal value
network alterations.
The project hypothesizes that the degree to which uncertainty modulates decision-making and learning
correlates with anxiety traits, mediated by specific cognitive computations and activity in different brain
networks in both healthy individuals and OCD patients.
We propose an experimental design involving two decision-making tasks under uncertainty (Ambiguity
Attitude-Management task and Learning under Uncertainty task), neuroimaging techniques (fMRI and DTI),
non-invasive brain stimulation (TMS), and EEG to explore the proposed neuronal and cognitive pathways.
Additionally, the study will involve two participant groups: healthy controls and patients with OCD to test our
hypothesis. This approach aims to explore cognitive and neuronal mechanisms linking uncertainty to anxiety
and to establish whether these pathways represent mediated processing of uncertainty and anxiety,
understanding anxiety as a transdiagnostic symptom.
Our cognitive tasks aim to distinguish between Uncertainty Aversion, Uncertainty Management, and Learning
Under Uncertainty. Functional MRI, EEG, TMS, and computational cognitive modeling will be employed to
study brain activity in three different networks, testing their causal mechanisms in processing uncertainty.
Exploring the consistency in the relationship between the proposed neuronal representation and anxiety in
both healthy individuals and patients with OCD will provide insights into the transdiagnostic mechanisms of
anxiety. Additionally, Comparing OCD patients and healthy controls will shed light on the specific mechanisms
underlying decision-making impairments in OCD.
This project aims to provide causal evidence of how different brain networks contribute to decision-making
under uncertainty and its link with anxiety in healthy individuals and OCD patients. The findings could inform
the development of targeted, non-invasive brain stimulation therapies for anxiety, enhancing mental health
treatment and patient outcomes.
Keywords
Fields of Science and Technology (OECD)
Medical and Health sciences
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