Failing as Doorman and Disc Jockey at the Same Time: Amygdalar Dysfunction in Parkinson’s Disease

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, medicationinduced 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. VC 2015 International Parkinson and Movement Disorder Society