For researchers who meet the criteria for access to the data access to the ADNI data is available through an online application, which can be submitted at the following link. All data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database ( ). This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: This study used baseline structural magnetic resonance images (MRI) and diffusion weighted MRI (DW-MRI) corresponding to 41 Alzheimer's patients. Received: NovemAccepted: ApPublished: May 24, 2018Ĭopyright: © 2018 Sanchez-Rodriguez et al. PLoS Comput Biol 14(5):Įditor: Saad Jbabdi, Oxford University, UNITED KINGDOM (2018) Design of optimal nonlinear network controllers for Alzheimer's disease.
Although focused on Alzheimer’s in this study, our methodology could be applied to other clinical conditions characterized by abnormalities in brain dynamics, like epilepsy and Parkinson’s, the treatment of which can benefit from the use of optimal control strategies.Ĭitation: Sanchez-Rodriguez LM, Iturria-Medina Y, Baines EA, Mallo SC, Dousty M, Sotero RC, et al. Our approach leads to the identification of potential target regions and subjects to successfully respond to brain stimulation therapies and yields various disease-reverting signals. This is the first time, to our knowledge, that brain stimulation for the most common cause of dementia, Alzheimer’s disease, is theoretically addressed. Amid the current efforts for developing personalized medicine, we introduce a framework for producing tailored stimulation signals, based on individual neuroimaging data and innovative modeling. Previous modeling approaches for stimulation have overlooked the nonlinear dynamical nature of the brain and failed to shed light on efficient mechanisms for the exogenous control of the brain. This work aims to close the knowledge gap between theory and experiment in brain stimulation. Other diseases associated with alterations in brain dynamics and the self-control mechanisms of the brain can be addressed through our framework. Patients with highly integrated anatomical networks–namely, networks having low average shortest path length, high global efficiency–are the most suitable candidates for the propagation of stimuli and consequent success on the control task. We also found that limbic system and basal ganglia structures constitute the top target locations for stimulation in AD. There are changes to the way stimulated regions are ranked in terms of the energetic cost of controlling the entire network, from a linear to a nonlinear approach. By considering nonlinearities in our model, we identified regions for which control inputs fail to correct abnormal activity. The nonlinear nature of the brain dynamics is preserved, given that we extend the so-called state-dependent Riccati equation control to reflect the stimulation objective in the high-dimensional neural system. We used anatomical networks obtained from diffusion magnetic resonance images acquired by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) as mediators for the interaction between Duffing oscillators. In this study, we introduce a control theory framework for obtaining exogenous signals that revert pathological electroencephalographic activity in AD at a minimal energetic cost, while reflecting patients’ biological variability. However, all individuals with the same condition currently receive identical brain stimulation, with limited theoretical basis for this generic approach. It is open label in the sense that they know what they are eating.Brain stimulation can modulate the activity of neural circuits impaired by Alzheimer’s disease (AD), having promising clinical benefit. Note on masking: The title of the study presented to participants is "IONsport: Women and Protein" and the funding source is withheld to mask from participants our underlying hypothesis. Study participants will be randomized to either one serving of beef or a macronutrient equivalent "veggie patty" per day for 30 days. Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information Why Should I Register and Submit Results?.