title: GABA content within medial prefrontal cortex predicts the variability of fronto-limbic effective connectivity.
abstract: 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.
authors.affiliation: Department of Neuroscience, Imaging and Clinical Sciences, University "G. d'Annunzio" of Chieti-Pescara, Via dei Vestini, 66100, Chieti, Italy.|Institute for Advanced Biomedical Technologies (ITAB), "G. d'Annunzio" University, Chieti-Pescara, Italy.|Center of Aging Sciences and Translational Medicine (CeSI-MeT), University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Delli Pizzi
authors.affiliation: Department of Neuroscience, Imaging and Clinical Sciences, University "G. d'Annunzio" of Chieti-Pescara, Via dei Vestini, 66100, Chieti, Italy.|Institute for Advanced Biomedical Technologies (ITAB), "G. d'Annunzio" University, Chieti-Pescara, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Chiacchiaretta
authors.affiliation: Research Centre for Motor Control and Neuroplasticity, KU Leuven, Heverlee, Belgium.|Department of Health Sciences and Technology, Neural Control of Movement Lab, Zurich, Switzerland.|Department of Experimental Psychology, Oxford University, Oxford, UK.
authors.forename: Dante
authors.initials: D
authors.lastname: Mantini
authors.affiliation: Department of Neuroscience, Imaging and Clinical Sciences, University "G. d'Annunzio" of Chieti-Pescara, Via dei Vestini, 66100, Chieti, Italy.|Institute for Advanced Biomedical Technologies (ITAB), "G. d'Annunzio" University, Chieti-Pescara, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Bubbico
authors.affiliation: Russell H. Morgan Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.|F.M. Kirby Center for Functional MRI, Kennedy Krieger Institute, Baltimore, MD, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Edden
authors.affiliation: Department of Neuroscience, Imaging and Clinical Sciences, University "G. d'Annunzio" of Chieti-Pescara, Via dei Vestini, 66100, Chieti, Italy.|Center of Aging Sciences and Translational Medicine (CeSI-MeT), University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Onofrj
authors.affiliation: Department of Neuroscience, Imaging and Clinical Sciences, University "G. d'Annunzio" of Chieti-Pescara, Via dei Vestini, 66100, Chieti, Italy.|Institute for Advanced Biomedical Technologies (ITAB), "G. d'Annunzio" University, Chieti-Pescara, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ferretti
authors.affiliation: Department of Neuroscience, Imaging and Clinical Sciences, University "G. d'Annunzio" of Chieti-Pescara, Via dei Vestini, 66100, Chieti, Italy. l.bonanni@unich.it.|Center of Aging Sciences and Translational Medicine (CeSI-MeT), University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy. l.bonanni@unich.it.
authors.forename: Laura
authors.identifier: http://orcid.org/0000-0003-4075-0132
authors.initials: L
authors.lastname: Bonanni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001288:Attention; D001931:Brain Mapping; D003071:Cognition / Q000502:physiology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007802:Language; D008032:Limbic System / Q000000981:diagnostic imaging / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000502:physiology*; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D011569:Psychiatric Status Rating Scales; D014316:Tritium / Q000493:pharmacokinetics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D014316:Tritium; D005680:gamma-Aminobutyric Acid
keywords: Amygdala; Anxiety; Emotions; Medial prefrontal cortex (mPFC); γ-Aminobutyric acid (GABA)