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.
