Deep brain stimulation for Parkinson's disease dissociates mood and motor circuits: A functional MRI case study

Abstract

Behavioral disturbances have been reported with subthalamic (STN) deep brain stimulation (DBS) treatment in Parkinson's disease (PD). We report correlative functional imaging (fMRI) of mood and motor responses induced by successive right and left DBS. A 36-year-old woman with medically refractory PD and a history of clinically remitted depression underwent uncomplicated implantation of bilateral STN DBS. High-frequency stimulation of the left electrode improved motor symptoms. Unexpectedly, right DBS alone elicited several reproducible episodes of acute depressive dysphoria. Structural and functional magnetic resonance imaging (fMRI) imaging was carried out with sequential individual electrode stimulation. The electrode on the left was within the inferior STN, whereas the right electrode was marginally superior and lateral to the intended STN target within the Fields of Forel/zona incerta. fMRI image analysis (Analysis of Functional NeuroImages, AFNI) contrasting OFF versus ON stimulation identified significant lateralized blood oxygen level-dependent (BOLD) signal changes with DBS (P < 0.001). Left DBS primarily showed changes in motor regions: increases in premotor and motor cortex, ventrolateral thalamus, putamen, and cerebellum as well as decreases in sensorimotor/supplementary motor cortex. Right DBS showed similar but less extensive change in motor regions. More prominent were the unique increases in superior prefrontal cortex, anterior cingulate (Brodmann's area [BA] 24), anterior thalamus, caudate, and brainstem, and marked widespread decreases in medial prefrontal cortex (BA 9/10). The mood disturbance resolved spontaneously in 4 weeks despite identical stimulation parameters. Transient depressive mood induced by subcortical DBS stimulation was correlated with changes in mesolimbic cortical structures. This case provides new evidence supporting cortical segregation of motor and nonmotor cortico-basal ganglionic systems that may converge in close proximity at the level of the STN and the adjacent white matter tracts (Fields of Forel/zona incerta).

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

“…Mood problems are more common in patients treated with STN-DBS than those treated with GPi-DBS Follett et al, 2010;Moro et al, 2010;Bronstein et al, 2011). Although the underlying substrate of these side effects remains to be characterized, it has been suggested that they may be induced by stimulation in non-motor areas of STN or GPi, inadvertent involvement of limbic structures outside of the target regions (Bejjani et al, 1999;Krack and Vercueil, 2001;Kulisevsky et al, 2002;Romito et al, 2002;Herzog et al, 2003a;Okun et al, 2003;Stefurak et al, 2003), and preexisting psychiatric conditions (Lilleeng and Dietrichs, 2008). Although significant unpleasant mood side effects following STN or GPi DBS are relatively rare (Funkiewiez et al, 2004;Castelli et al, 2006;Tir et al, 2007), their occurrence significantly disrupts patients' quality of life.…”

A three-dimensional, histological and deformable atlas of the human basal ganglia. I. Atlas construction based on immunohistochemical and MRI data

“…(For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.) mood responses are obtained by stimulation of different parts of the STN in human parkinsonian patients (MacKinnon et al, 2005;Mallet et al, 2002;Stefurak et al, 2003). However, it must be remembered that the relative size of the territories could be different in the two species.…”

Deep brain stimulation in Parkinson disease—what went wrong?

“…The STN and mood Depression, apathy and anxiety can arise as complications after surgery [60][61][62][63] and rare cases of acute stimulationinduced depressed mood have been reported [57,58]. However, the vast majority of cases with an acute emotional response to STN DBS exhibit hypomania [50] or mania [25,52].…”