How to deal with climate change related trauma and anxiety Neurostimulation as a new frontier of treatment

The ongoing climate crisis is not only an environmental challenge but also a growing threat to individuals’ mental health and well-being. Climate anxiety is now a widespread phenomenon characterized by chronic anticipatory distress and physiological hyperarousal, while the rising exposure to environmental disasters is leading to increased rates of posttraumatic stress disorder (PTSD). Hence, understanding the neural mechanisms through which defensive and memory systems –which are deeply intertwined and adaptively ensure survival– may be dysregulated, and emotional memories related to dangerous experiences may become maladaptive, is essential to deal with these emerging forms of suffering. The main purpose of this thesis was to test whether neurostimulation of the prefrontal cortex (PFC) through repetitive transcranial magnetic stimulation (rTMS) can downregulate defensive alarm reactions to learned threat-predictive stimuli and threat generalization in a sample of healthy low-anxiety participants and individuals reporting high trait anxiety levels. Across three distinct experimental studies, we combined psychophysiological, cognitive, and neuromodulatory approaches to explore the mechanisms underpinning implicit and explicit threat memories and their dysregulation in vulnerable populations. In the first study (n = 172, mixed between-within design), we demonstrated that a single session of low-frequency (1 Hz) rTMS over the anterior prefrontal cortex (aPFC, BA 10) enduringly downregulated implicit defensive responses to learned threats in low-anxiety individuals (ηp 2 = 0.188), preventing the spontaneous recovery and contextual renewal of fear over time. In the second study (n = 85, mixed between-within design), we showed that high trait anxiety widens generalization of defensive responses to new stimuli, reflected in both undecomposed and phasic autonomic reactions, while tonic activity revealed globally heightened sympathetic arousal. However, a single aPFC-rTMS session did not significantly modulate these anxiety-related patterns, suggesting that enduring trait anxiety may limit the efficacy of this protocol targeting traumatic-like memories. In the third study (n = 32, mixed between-within design), we found that individuals with obesity −a clinical condition associated with emotional vulnerability− exhibited widened autonomic threat generalization despite unaffected threat learning (ηp 2 = 0.184) and explicit memory, pointing to shared prefrontal– subcortical mechanisms underlying dysregulated defensive behavior. Collectively, these findings identify the aPFC as a key node in the regulation of implicit defensive reactivity and highlight the need for refined, multi-session, and personalized neurostimulation strategies to treat persistent hyperarousal and overgeneralization. By linking laboratory models to real-world phenomena, this work contributes to understanding and mitigating the neural basis of maladaptive defensive states, offering translational insights for clinical conditions such as PTSD and the growing phenomenon of climate anxiety, in which fear and memory intertwine to shape human responses to an increasingly uncertain world