Dopamine in amygdala gates limbic processing of aversive stimuli in humans

Abstract

Dopamine is released under stress and modulates processing of aversive stimuli. We found that dopamine storage capacity in human amygdala, measured with 6-[ 18 F]fluoro-L-DOPA positron emission tomography, was positively correlated with functional magnetic resonance imaging blood oxygen leveldependent signal changes in amygdala and dorsal anterior cingulate cortex that were evoked by aversive stimuli. Furthermore, functional connectivity between these two regions was inversely related to trait anxiety. Our results suggest that individual dopamine storage capacity in amygdala subserves modulation of emotional processing in amygdala and dorsal cingulate, thereby contributing to individual differences in anxious temperament.An emphasis is frequently placed on the importance of dopamine in shaping complex behavior and in regulating neural responses to rewarding stimuli 1 , often overshadowing its contribution to aversive processing [2][3][4] . Animal studies demonstrate that dopamine release in the amygdala augments excitatory sensory input and attenuates inhibitory prefrontal input, resulting in augmented aversive conditioning 5 . Consistent with these findings, human pharmacological neuroimaging studies show that increased dopamine release potentiates human amygdala function 6,7 . These convergent findings suggest that variability in dopamine signaling may contribute to individual variability in amygdala function and related emotional behaviors.Blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is an effective and reliable tool for measuring stable individual differences in amygdala function 8 . Positron emission tomography (PET) recordings with 6-[ 18 F]fluoro-L-DOPA (FDOPA) provide the basis for calculating the net influx of FDOPA to the brain relative to the metabolite-corrected plasma input (K in app ; ml g -1 min -1 ) and steady-state distribution volume in brain of FDOPA (V d ; ml g -1 ), defined below.We used combined BOLD fMRI and FDOPA-PET to examine the relationship between regional dopamine storage and functional reactivity to affective visual cues in the amygdala and in the functionally coupled anterior cingulate cortex (ACC) in 13 healthy adult men 9-11 . All subjects provided informed written consent according to the declaration of Helsinki and the study was approved by the local ethics committee of the We used event-related BOLD fMRI to measure amygdala reactivity during the passive viewing of standardized affectively negative and neutral visual stimuli (Supplementary Methods). The general linear model in SPM5 (Statistical Parametric Mapping, see Supplementary Methods) was used to calculate single-subject activation for the contrast of negative versus neutral stimuli. Consistent with prior studies (for example, see ref. 12), the presentation of negative versus neutral stimuli elicited significant activation in the left amygdala (x ¼ -21, y ¼ -1, z ¼ -15; t ¼ 3.23, P ¼ 0.036, FWE (family-wise error) corrected for volume of interest). We next examined functional coupling ...

Contribution of Dopamine D1 and D2 Receptors to Amygdala Activity in Human

“…We found that DA D1 receptors, but not D2 receptors, predicted amygdala response induced by novel facial stimuli with either neutral or fearful expression. Our findings broaden our knowledge about dopaminergic transmission in amygdala response beyond the recent study (Kienast et al, 2008) that elucidated the relation between presynaptic dopamine synthesis and amygdala reactivity.…”

“…In addition, another fMRI study of healthy volunteers has demonstrated that amphetamine potentiated the response of the amygdala during an emotional task . More recently, Kienast et al (2008) reported that dopamine storage capacity in human amygdala, measured with 6-[…”

Effect of Schizophrenia Risk-Associated Alleles in SREB2 (GPR85) on Functional MRI Phenotypes in Healthy Volunteers

“…fMRI paradigms. FMT based on emotion identity recognition, this task, originally developed by Hariri et al (2000), has been widely used by our group and others (Hariri et al, 2002;Kienast et al, 2008) and has been shown to strongly engage the amygdala and HF. The subjects underwent two experimental conditions: emotional identity face matching and a sensorimotor task.…”

Errors recruit both cognitive and emotional monitoring systems: Simultaneous intracranial recordings in the dorsal anterior cingulate gyrus and amygdala combined with fMRI

“…There are also strong anatomical connections between rostral parts of ACC and other limbic structures involved in affect and motivation, such as the amygdala and insula (van Hoesen, Morecraft, & Vogt, 1993;Ongur & Price, 2000; see also Ochsner & Gross, 2005;Kienast et al, 2008). Based on this evidence, some theories proposed that ACC activity following errors could also reflect an appraisal of the affective significance or salience of errors (Luu, Tucker, Derryberry, Reed, & Poulsen, 2003;Hajcak, Moser, Yeung, & Simons, 2005;Pizzagalli, Peccoralo, Davidson, & Cohen, 2006;Taylor et al, 2006;Polli et al, 2008Polli et al, , 2009Li et al, 2008;Hajcak & Foti, 2008).…”

“…Further, in a recent scalp ERP study in healthy participants, Hajcak & Foti (2008) found that the startle blink reflex was enhanced following errors during a flanker task, suggesting that error monitoring could also activate the defensive motivational system responsible for the startle reflex (Lang, Bradley, & Cuthbert, 1990). Because both the amygdala and insula are implicated in anxiety and defensive behaviors, these limbic regions might also contribute to error detection processes taking place in dorsal ACC (Ochsner & Gross, 2005;Fales et al, 2008;Kienast et al, 2008). Indirect evidence in support of this theory comes from a few neuroimaging studies that showed increased activity to errors not only in ACC and PFC, but also in deeper limbic brain structures such as the amygdala, insula, and thalamus (Menon, Adleman, White, Glover, & Reiss, 2001;Garavan, Ross, Murphy, Roche, & Stein, 2002;Polli et al, 2008;Li et al, 2008).…”