Aim 1: Determine the relationship between active contact location and acute mood responses to STN DBS. We hypothesize that stimulation near ventromedial STN will induce more acute change in mood than stimulation near dorsal STN. This finding would indicate that there is functional heterogeneity within the STN for mood. In addition, there may be a lateralized effect to these mood changes such that positively valenced mood will increase temporarily with right STN stimulation more than left, and vice-versa for negatively valenced mood. We will employ a novel, validated atlas-based registration technique to pre and post-surgical brain images to identify the location of contacts relative to the STN. STN DBS patients will then perform a mood assessment battery while contacts within the STN are activated.

Aim 2: Determine whether acute mood responses to STN stimulation are different in patients with past or current mood or anxiety disorders. We hypothesize that acute increases in negatively valenced mood in response to stimulation of ventromedial STN will be more significant in patients with a history of or with current clinically significant depression and anxiety, as measured with structured clinical interviews and self- and proxy-reports. This finding would indicate that STN circuitry dysfunction is influenced by (or precedes) clinical mood and/or anxiety disorders.

Aim 3: Determine whether acute mood changes with STN DBS predict risk for future, clinically significant mood or anxiety disorders. We hypothesize that patients who experience acute increases in negatively valenced mood in response to stimulation of ventromedial STN may also be more likely to develop clinically significant chronic depression or anxiety in the future. This finding would indicate that a vulnerability of the neural circuits underlying mood dysfunction can be detected through a stimulation challenge paradigm. We propose to follow STN DBS patients prospectively, assessing emerging psychiatric problems with structured clinical interviews and self- and proxy-reports. A non-DBS PD group will also be followed to determine if STN DBS patients are representative of the PD population in terms of risk for developing mood or anxiety disorders.