Pharmacologic activation of limbic structures and neuroimaging studies of emotions

Two primary paradigms have been employed to study the neurobiological basis of human emotions. These are induced emotions in normal subjects and the comparison of patients suffering from emotional disorders with normal control subjects. These traditional methods, which have limitations, may be complemented by a third approach: the experimental elicitation of affect through pharmacologic limbic stimulation with intravenous procaine hydrochloride. In this paper, the authors review their research using the direct stimulation approach. To determine whether procaine produces affectively laden experiences accompanied by a reliable change in brain activity, 10 normal subjects received two injections each of placebo (A) and procaine (B)-in ABBA order-while in a positron emission tomography (PET) scanner. In a further study, emotional responses were observed among 24 subjects (including the 10 subjects in the PET study) for a total of 80 procaine injections. Procaine was shown to induce bilateral activation of an anterior limbic network concomitant with powerful, transient emotional and other subjective phenomena as well as autonomic and endocrine responses. Considerable between-subject variability in responses was noted, suggesting that this method can be used to explore individual differences in the neurobiological basis of emotion and affective disposition. Experimental elicitation of affect through limbic stimulation with procaine, when used as part of a triangulation strategy with traditional imaging paradigms, can contribute to our understanding of emotion and its disorders, of the different components of emotion-response systems (e.g., subjective, autonomic, and endocrine), and of individual differences in affective disposition.