TY - JOUR
T1 - GABA content within medial prefrontal cortex predicts the variability of fronto-limbic effective connectivity
AU - Delli Pizzi, Stefano
AU - Chiacchiaretta, Piero
AU - Mantini, Dante
AU - Bubbico, Giovanna
AU - Edden, Richard A.
AU - Onofrj, Marco
AU - Ferretti, Antonio
AU - Bonanni, Laura
N1 - Funding Information:
Acknowledgements The work has been supported by the Italian Ministry of Health (Grant No. GR-2010-2313418) and the Wellcome Trust (Grant No. 101253/A/13/Z). This study applies tools developed under NIH R01 EB016089 and P41 EB015909; RAEE also receives salary support from these grants.
Publisher Copyright:
© Springer-Verlag Berlin Heidelberg 2017.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - The amygdala-medial prefrontal cortex (mPFC) circuit plays a key role in social behavior. The amygdala and mPFC are bidirectionally connected, functionally and anatomically, via the uncinate fasciculus. Recent evidence suggests that GABA-ergic neurotransmission within the mPFC could be central to the regulation of amygdala activity related to emotions and anxiety processing. However, the functional and neurochemical interactions within amygdala-mPFC circuits are unclear. In the current study, multimodal magnetic resonance imaging techniques were combined to investigate effective connectivity within the amygdala-mPFC network and its relationship with mPFC neurotransmission in 22 healthy subjects aged between 41 and 88 years. Effective connectivity in the amygdala-mPFC circuit was assessed on resting-state functional magnetic resonance imaging data using spectral dynamic causal modelling. State and trait anxiety were also assessed. The mPFC was shown to be the target of incoming outputs from the amygdalae and the source of exciting inputs to the limbic system. The amygdalae were reciprocally connected by excitatory projections. About half of the variance relating to the strength of top-down endogenous connection between right amygdala and mPFC was explained by mPFC GABA levels. State anxiety was correlated with the strength of the endogenous connections between right amygdala and mPFC. We suggest that mPFC GABA content predicts variability in the effective connectivity within the mPFC-amygdala circuit, providing new insights on emotional physiology and the underlying functional and neurochemical interactions.
AB - The amygdala-medial prefrontal cortex (mPFC) circuit plays a key role in social behavior. The amygdala and mPFC are bidirectionally connected, functionally and anatomically, via the uncinate fasciculus. Recent evidence suggests that GABA-ergic neurotransmission within the mPFC could be central to the regulation of amygdala activity related to emotions and anxiety processing. However, the functional and neurochemical interactions within amygdala-mPFC circuits are unclear. In the current study, multimodal magnetic resonance imaging techniques were combined to investigate effective connectivity within the amygdala-mPFC network and its relationship with mPFC neurotransmission in 22 healthy subjects aged between 41 and 88 years. Effective connectivity in the amygdala-mPFC circuit was assessed on resting-state functional magnetic resonance imaging data using spectral dynamic causal modelling. State and trait anxiety were also assessed. The mPFC was shown to be the target of incoming outputs from the amygdalae and the source of exciting inputs to the limbic system. The amygdalae were reciprocally connected by excitatory projections. About half of the variance relating to the strength of top-down endogenous connection between right amygdala and mPFC was explained by mPFC GABA levels. State anxiety was correlated with the strength of the endogenous connections between right amygdala and mPFC. We suggest that mPFC GABA content predicts variability in the effective connectivity within the mPFC-amygdala circuit, providing new insights on emotional physiology and the underlying functional and neurochemical interactions.
KW - Amygdala
KW - Anxiety
KW - Emotions
KW - Medial prefrontal cortex (mPFC)
KW - γ-Aminobutyric acid (GABA)
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U2 - 10.1007/s00429-017-1399-x
DO - 10.1007/s00429-017-1399-x
M3 - Article
C2 - 28386778
AN - SCOPUS:85017190496
SN - 1863-2653
VL - 222
SP - 3217
EP - 3229
JO - Brain Structure and Function
JF - Brain Structure and Function
IS - 7
ER -