Revaluing the Role of vmPFC in the Acquisition of Pavlovian Threat Conditioning in Humans

• Published in: The Journal of neuroscience 2020-10, Vol.40 (44), p.8491-8500
• Main Authors: Battaglia, Simone, Garofalo, Sara, di Pellegrino, Giuseppe, Starita, Francesca
• Format: Article
• Language: English
• Subjects: Adult; Aged; Brain Injuries - diagnostic imaging; Brain Injuries - physiopathology; Brain Injuries - psychology; Brain Mapping; Classical conditioning; Conditioning; Conditioning, Classical - physiology; Conductance; Extinction behavior; Extinction, Psychological; Fear - physiology; Female; Galvanic Skin Response - physiology; Humans; Learning; Lesions; Magnetic Resonance Imaging; Male; Medical imaging; Memory - physiology; Middle Aged; Neuroimaging; Neuropsychological Tests; Prefrontal cortex; Prefrontal Cortex - diagnostic imaging; Prefrontal Cortex - injuries; Prefrontal Cortex - physiology; Resistance; Reversal learning; Skin conductance response; Unconditioned stimulus
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.0304-20.2020

The role of the ventromedial prefrontal cortex (vmPFC) in human pavlovian threat conditioning has been relegated largely to the extinction or reversal of previously acquired stimulus-outcome associations. However, recent neuroimaging evidence questions this view by also showing activity in the vmPFC during threat acquisition. Here we investigate the casual role of vmPFC in the acquisition of pavlovian threat conditioning by assessing skin conductance response (SCR) and declarative memory of stimulus-outcome contingencies during a differential pavlovian threat-conditioning paradigm in eight patients with a bilateral vmPFC lesion, 10 with a lesion outside PFC and 10 healthy participants (each group included both females and males). Results showed that patients with vmPFC lesion failed to produce a conditioned SCR during threat acquisition, despite no evidence of compromised SCR to unconditioned stimulus or compromised declarative memory for stimulus-outcome contingencies. These results suggest that the vmPFC plays a causal role in the acquisition of new learning and not just in the extinction or reversal of previously acquired learning, as previously thought. Given the role of the vmPFC in schema-related processing and latent structure learning, the vmPFC may be required to construct a detailed representation of the task, which is needed to produce a sustained conditioned physiological response in anticipation of the unconditioned stimulus during threat acquisition. Pavlovian threat conditioning is an adaptive mechanism through which organisms learn to avoid potential threats, thus increasing their chances of survival. Understanding what brain regions contribute to such a process is crucial to understand the mechanisms underlying adaptive as well as maladaptive learning, and has the potential to inform the treatment of anxiety disorders. Importantly, the role of the ventromedial prefrontal cortex (vmPFC) in the acquisition of pavlovian threat conditioning has been relegated largely to the inhibition of previously acquired learning. Here, we show that the vmPFC actually plays a causal role in the acquisition of pavlovian threat conditioning.