Periodic Reporting for period 4 - DARE2APPROACH (Dare to Approach: A Neurocognitive Approach to Alleviating Persistent Avoidance in Anxiety Disorders)
Période du rapport: 2023-07-01 au 2024-11-30
Anxiety disorders are among the most common mental disorders forming a serious burden for the individual, and the society at large. Because avoidance behaviour is a major causal and maintaining factor in anxiety disorders, the central aim of DARE2APPRAOCH is to understand and alleviate persistent avoidance behaviour in anxious individuals. Although avoidance during a threatening situation has the immediate benefit of causing relief, it comes with serious costs in the long run. For instance, as long as a patient with social anxiety avoids social situations, the anxiety cannot extinguish and one misses out on important opportunities, for instance to meet significant others or to obtain a job.
Current interventions for anxiety disorders often fail because we lack understanding of how anxious individuals make approach-avoidance decisions and how their brains weigh the consequences of approach versus avoidance. Moreover, perceived threat elicits psychophysiological changes, such as freezing, that affect approach-avoidance decision making. However, due to a lack of integration between knowledge from decision neuroscience on the one hand and knowledge from the field of emotional-action control on the other hand, current neurocomputational models of approach-avoidance decisions do not consider those bodily states during acute threat. As a consequence, those models are not optimized to inform new interventions into persistent anxiety. Therefore, our objectives were to 1) develop a neurocomputational model of approach-avoidance (AA) decisions that accounts for the psychophysiological states of the decision maker; 2) to define how neural control over avoidance decisions is altered in anxious individuals, and 3) based on that to developed a neurocognitively grounded intervention to improve decision making in healthy individuals and in patients with anxiety symptoms.
Current interventions for anxiety disorders often fail because we lack understanding of how anxious individuals make approach-avoidance decisions and how their brains weigh the consequences of approach versus avoidance. Moreover, perceived threat elicits psychophysiological changes, such as freezing, that affect approach-avoidance decision making. However, due to a lack of integration between knowledge from decision neuroscience on the one hand and knowledge from the field of emotional-action control on the other hand, current neurocomputational models of approach-avoidance decisions do not consider those bodily states during acute threat. As a consequence, those models are not optimized to inform new interventions into persistent anxiety. Therefore, our objectives were to 1) develop a neurocomputational model of approach-avoidance (AA) decisions that accounts for the psychophysiological states of the decision maker; 2) to define how neural control over avoidance decisions is altered in anxious individuals, and 3) based on that to developed a neurocognitively grounded intervention to improve decision making in healthy individuals and in patients with anxiety symptoms.
Our concrete work can be best summarized along two important research lines that have each led to important publications, theoretical, methodological breakthrough and has had significant exploitation in clinical practice.
1) To test what brain mechanisms enable people to override automatic avoidance tendencies and how this fails in anxiety patients, we applied approach-avoidance tasks combined with various neuroimaging and neuromodulation techniques, looking at functional brain connectivity, structural connections in the brain, chemical reactions but also by directly manipulating brain connectivity (neuromodulation). The results show that anxious individuals indeed show difficulty to override their automatic avoidance tendencies and to approach a situation, for instance to achieve a goal. We revealed the neural mechanisms underlying this failure: In contrast to previous accounts, their anterior prefrontal cortex does not show reduced activation but is over-excitable, due to increased inputs from subcortical brain regions, including the amygdala. We detected alterations in chemical, structural and functional brain mechanisms and detected a compensatory mechanism by which anxiety patients can still function relatively well in mildly stressful situations (Bramson ea Roelofs, Nature Communications 2023). However, this mechanism is less able to deal with highly demanding situations, potentially explaining their failure in decision making in highly stressful situations. These insights led to direct implications for novel interventions that do not only improve emotion control in healthy individuals (Bramson ea Roelofs, eLife 2020) but also in anxious individuals (Meijer ea Roelofs, bioRxiv). The intervention (called dual-site transcranial alternating stimulation, in short dual-site-tACS) improves synchronicity between frontal and motor regions in the brain, while at the same time impacting activity in the amygdala. In terms of dissemination, it is relevant to mention that we are currently testing if the intervention can enhance efficacy of exposure therapy for anxiety patients together with mental health organisations. The insights have also led to theoretical innovations (Roelofs ea., New York Academy of Sciences, 2023; Bramson ea, NBBR, 2023).
2) In terms of neurocomputational models, we invested in task and model development and revealed that bodily states (such as freezing-induced bradycardia) impact how we weigh the costs and benefits when we make approach-avoidance decisions under threat (Klaassen ea Roelofs, 2024 Comm Biology). As a brief background, our autonomic nervous system has two branches, a sympathetic branch hat brings us in a fight/flight state and is associated with increased heart rate and a parasympathetic branch that is associated with freeze and decreased heart rate (bradycardia) under threat. Using computational models of decision making we showed that those bodily states impact how we weigh the costs and benefits in a situation of approach-avoidance conflict: Sympathetic dominance in highly anxious hampers to override persistent avoidance, and thereby hinders to obtain a reward or to achieve a longer term goal. These findings have direct implications for future research and development of tailored intervention. It has for instance led to a VR-based biofeedback training to optimize decisions under threat by improving the heart rhythm.
In total the project has led to 36 publications (including in Nature Human Behaviour, Nature Communications, Nature Reviews Neuroscience, PNAS), significant media coverage (including, radio television and news papers), patent applications, novel methods (passive-active avoidance (PAT)-task, dual-site tACS, VR-based biofeedback training). The work has also led to clinical breakthroughs and our methods are currently used to enhance efficacy of exposure therapy.
1) To test what brain mechanisms enable people to override automatic avoidance tendencies and how this fails in anxiety patients, we applied approach-avoidance tasks combined with various neuroimaging and neuromodulation techniques, looking at functional brain connectivity, structural connections in the brain, chemical reactions but also by directly manipulating brain connectivity (neuromodulation). The results show that anxious individuals indeed show difficulty to override their automatic avoidance tendencies and to approach a situation, for instance to achieve a goal. We revealed the neural mechanisms underlying this failure: In contrast to previous accounts, their anterior prefrontal cortex does not show reduced activation but is over-excitable, due to increased inputs from subcortical brain regions, including the amygdala. We detected alterations in chemical, structural and functional brain mechanisms and detected a compensatory mechanism by which anxiety patients can still function relatively well in mildly stressful situations (Bramson ea Roelofs, Nature Communications 2023). However, this mechanism is less able to deal with highly demanding situations, potentially explaining their failure in decision making in highly stressful situations. These insights led to direct implications for novel interventions that do not only improve emotion control in healthy individuals (Bramson ea Roelofs, eLife 2020) but also in anxious individuals (Meijer ea Roelofs, bioRxiv). The intervention (called dual-site transcranial alternating stimulation, in short dual-site-tACS) improves synchronicity between frontal and motor regions in the brain, while at the same time impacting activity in the amygdala. In terms of dissemination, it is relevant to mention that we are currently testing if the intervention can enhance efficacy of exposure therapy for anxiety patients together with mental health organisations. The insights have also led to theoretical innovations (Roelofs ea., New York Academy of Sciences, 2023; Bramson ea, NBBR, 2023).
2) In terms of neurocomputational models, we invested in task and model development and revealed that bodily states (such as freezing-induced bradycardia) impact how we weigh the costs and benefits when we make approach-avoidance decisions under threat (Klaassen ea Roelofs, 2024 Comm Biology). As a brief background, our autonomic nervous system has two branches, a sympathetic branch hat brings us in a fight/flight state and is associated with increased heart rate and a parasympathetic branch that is associated with freeze and decreased heart rate (bradycardia) under threat. Using computational models of decision making we showed that those bodily states impact how we weigh the costs and benefits in a situation of approach-avoidance conflict: Sympathetic dominance in highly anxious hampers to override persistent avoidance, and thereby hinders to obtain a reward or to achieve a longer term goal. These findings have direct implications for future research and development of tailored intervention. It has for instance led to a VR-based biofeedback training to optimize decisions under threat by improving the heart rhythm.
In total the project has led to 36 publications (including in Nature Human Behaviour, Nature Communications, Nature Reviews Neuroscience, PNAS), significant media coverage (including, radio television and news papers), patent applications, novel methods (passive-active avoidance (PAT)-task, dual-site tACS, VR-based biofeedback training). The work has also led to clinical breakthroughs and our methods are currently used to enhance efficacy of exposure therapy.
The DARE2APPROACH project moved beyond the state in at least three ways: 1) From fear to avoidance: Providing a comprehensive neurocomputational model of persistent avoidance in anxiety disorders. 2) Concrete intervention to enhance treatment of anxiety disorders based on the newly derived mechanistic neurocognitive insights. 3) and the impact of DARE2APPRACH will go beyond improving insight into and interventions for anxiety disorders. The knowledge can also be used for other stress-related disorders, such as affective disorders and for individuals who have to make decisions under threat on a daily basis, such as primary responders, including police officers and fire workers. Indeed, the insights into the relation between bodily threat state (freezing-related bradycardia) and decision making have led to the development of a VR-based biofeedback training hat is currently being tested in police officers to improve decision making under stress.