Subthalamic deep brain stimulation sweet spots and hyperdirect cortical connectivity in Parkinson’s disease

Akram, Harith; Sotiropoulos, Stamatios N.; Jbabdi, Saad; Georgiev, Dejan; Mahlknecht, Philipp; Hyam, Jonathan; Foltynie, Thomas; Limousin, Patricia; De Vita, Enrico; Jahanshahi, Marjan; Hariz, Marwan; Ashburner, John; Behrens, Timothy; Zrinzo, Ludvic

Abstract

Objectives
Firstly, to identify subthalamic region stimulation clusters that predict maximum improvement in rigidity, bradykinesia and tremor, or emergence of side-effects; and secondly, to map-out the cortical fingerprint, mediated by the hyperdirect pathways which predict maximum efficacy.
Methods
High angular resolution diffusion imaging in twenty patients with advanced Parkinson’s disease was acquired prior to bilateral subthalamic nucleus deep brain stimulation. All contacts were screened one-year from surgery for efficacy and side-effects at different amplitudes. Voxel-based statistical analysis of volumes of tissue activated models was used to identify significant treatment clusters. Probabilistic tractography was employed to identify cortical connectivity patterns associated with treatment efficacy.
Results
All patients responded well to treatment (46% mean improvement off medication UPDRS-III [p<0.0001]) without significant adverse events. Cluster corresponding to maximum improvement in tremor was in the posterior, superior and lateral portion of the nucleus. Clusters corresponding to improvement in bradykinesia and rigidity were nearer the superior border in a further medial and posterior location. The rigidity cluster extended beyond the superior border to the area of the zona incerta and Forel-H2 field. When the clusters where averaged, the coordinates of the area with maximum overall efficacy was X=-10(-9.5), Y=-13(-1) and Z=-7(-3) in MNI(AC-PC) space. Cortical connectivity to primary motor area was predictive of higher improvement in tremor; whilst that to supplementary motor area was predictive of improvement in bradykinesia and rigidity; and connectivity to prefrontal cortex was predictive of improvement in rigidity.
Interpretation
These findings support the presence of overlapping stimulation sites within the subthalamic nucleus and its superior border, with different cortical connectivity patterns, associated with maximum improvement in tremor, rigidity and bradykinesia.

Citation

Akram, H., Sotiropoulos, S. N., Jbabdi, S., Georgiev, D., Mahlknecht, P., Hyam, J., Foltynie, T., Limousin, P., De Vita, E., Jahanshahi, M., Hariz, M., Ashburner, J., Behrens, T., & Zrinzo, L. (2017). Subthalamic deep brain stimulation sweet spots and hyperdirect cortical connectivity in Parkinson’s disease. NeuroImage, 158, https://doi.org/10.1016/j.neuroimage.2017.07.012

• Journal Article Type: Article
• Acceptance Date: Jul 9, 2017
• Online Publication Date: Jul 12, 2017
• Publication Date: Sep 1, 2017
• Deposit Date: Jul 12, 2017
• Publicly Available Date: Jul 12, 2017
• Journal: NeuroImage
• Print ISSN: 1053-8119
• Electronic ISSN: 1095-9572
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 158
• DOI: https://doi.org/10.1016/j.neuroimage.2017.07.012
• Keywords: Diffusion weighted imaging (DWI), connectivity, Parkinson’s disease (PD), subthalamic nucleus (STN), volume of tissue activated (VTA), hyperdirect pathway
• Public URL: https://nottingham-repository.worktribe.com/output/966437
• Publisher URL: http://www.sciencedirect.com/science/article/pii/S1053811917305803
• Contract Date: Jul 12, 2017