title: Failing as doorman and disc jockey at the same time: Amygdalar dysfunction in Parkinson's disease.
abstract: In Braak's model of ascending degeneration in Parkinson's disease (PD), involvement of the amygdala occurs simultaneously with substantia nigra degeneration. However, the clinical manifestations of amygdalar involvement in PD have not been fully delineated. Considered a multitask manager, the amygdala is a densely connected "hub," coordinating and integrating tasks ranging from prompt, multisensorial emotion recognition to adequate emotional responses and emotional tuning of memories. Although phylogenetically predisposed to handle fear, the amygdala handles both aversive and positive emotional inputs. In PD, neuropathological and in vivo studies suggest primarily amygdalar hypofunction. However, as dopamine acts as an inverted U-shaped amygdalar modulator, medication-induced hyperactivity of the amygdala can occur. We propose that amygdalar (network) dysfunction contributes to reduced recognition of negative emotional face expressions, impaired theory of mind, reactive hypomimia, and impaired decision making. Similarly, impulse control disorders in predisposed individuals, hallucinations, anxiety, and panic attacks may be related to amygdalar dysfunction. When available, we discuss amygdala-independent trigger mechanisms of these symptoms. Although dopaminergic agents have mostly an activation effect on amygdalar function, adaptive and compensatory network changes may occur as well, but these have not been sufficiently explored. In conclusion, our model of amygdalar involvement brings together several elements of Parkinson's disease phenomenology heretofore left unexplained and provides a framework for testable hypotheses in patients during life and in autopsy analyses.
authors.affiliation: Department of Neurosciences, Centre Hospitalier de Luxembourg, Luxembourg-City, Luxembourg.|Centre for Systems Biomedicine, University of Luxembourg, Campus Esch-Belval, Esch-s.-Alzette, Luxembourg.|Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Nico J
authors.initials: NJ
authors.lastname: Diederich
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Goldman
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Glenn T
authors.initials: GT
authors.lastname: Stebbins
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Goetz
mesh_terms: D000679:Amygdala / Q000473:pathology / Q000503:physiopathology*; D004644:Emotions / Q000502:physiology*; D006801:Humans; D010300:Parkinson Disease / Q000150:complications* / Q000473:pathology*; D010802:Phylogeny
keywords: amygdala; anxiety; emotional face recognition; hallucinations; impulse control disorders