Neural plasticity in human brain connectivity: the effects of long term deep brain stimulation of the subthalamic nucleus in Parkinson's disease.
BACKGROUND
Positive clinical outcomes are now well established for deep brain stimulation, but little is known about the effects of long-term deep brain stimulation on brain structural and functional connectivity. Here, we used the rare opportunity to acquire pre- and postoperative diffusion tensor imaging in a patient undergoing deep brain stimulation in bilateral subthalamic nuclei for Parkinson's Disease. This allowed us to analyse the differences in structural connectivity before and after deep brain stimulation. Further, a computational model of spontaneous brain activity was used to estimate the changes in functional connectivity arising from the specific changes in structural connectivity.


RESULTS
We found significant localised structural changes as a result of long-term deep brain stimulation. These changes were found in sensory-motor, prefrontal/limbic, and olfactory brain regions which are known to be affected in Parkinson's Disease. The nature of these changes was an increase of nodal efficiency in most areas and a decrease of nodal efficiency in the precentral sensory-motor area. Importantly, the computational model clearly shows the impact of deep brain stimulation-induced structural alterations on functional brain changes, which is to shift the neural dynamics back towards a healthy regime. The results demonstrate that deep brain stimulation in Parkinson's Disease leads to a topological reorganisation towards healthy bifurcation of the functional networks measured in controls, which suggests a potential neural mechanism for the alleviation of symptoms.


CONCLUSIONS
The findings suggest that long-term deep brain stimulation has not only restorative effects on the structural connectivity, but also affects the functional connectivity at a global level. Overall, our results support causal changes in human neural plasticity after long-term deep brain stimulation and may help to identify the underlying mechanisms of deep brain stimulation.
Center of Functionally Integrative Neuroscience (CFIN), Aarhus University, Aarhus, Denmark ; Department of Psychiatry, University of Oxford, Oxford, United Kingdom.
Tim J
TJ
van Hartevelt
Department of Psychiatry, University of Oxford, Oxford, United Kingdom ; Center of Brain and Cognition, Theoretical and Computational Neuroscience Group, Universitat Pompeu Fabra, Barcelona, Spain.
Joana
J
Cabral
Center of Brain and Cognition, Theoretical and Computational Neuroscience Group, Universitat Pompeu Fabra, Barcelona, Spain ; Institució Catalana de la Recerca i Estudis Avançats (ICREA), Universitat Pompeu Fabra, Barcelona, Spain.
Gustavo
G
Deco
Center of Functionally Integrative Neuroscience (CFIN), Aarhus University, Aarhus, Denmark.
Arne
A
Møller
Nuffield Department of Surgical Sciences, John Radcliffe Hospital, Oxford, United Kingdom.
Alexander L
AL
Green
Center of Functionally Integrative Neuroscience (CFIN), Aarhus University, Aarhus, Denmark ; Nuffield Department of Surgical Sciences, John Radcliffe Hospital, Oxford, United Kingdom.
Tipu Z
TZ
Aziz
Center of Functionally Integrative Neuroscience (CFIN), Aarhus University, Aarhus, Denmark ; Department of Psychiatry, University of Oxford, Oxford, United Kingdom.
Morten L
ML
Kringelbach
D000328:Adult; D000465:Algorithms; D001921:Brain / Q000503:physiopathology*; D016022:Case-Control Studies; D063132:Connectome; D046690:Deep Brain Stimulation; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D016571:Neural Networks, Computer; D009473:Neuronal Plasticity; D010300:Parkinson Disease / Q000503:physiopathology; D020531:Subthalamic Nucleus / Q000503:physiopathology; D055815:Young Adult