Neuromodulation for Depression: Insights Gained from Neuroimaging and Computational Models

Major depressive disorder (MDD) is a public health concern worldwide, affecting a sixth of the American population. Neuromodulation therapies have been employed to treat severe cases of treatment resistant depression. These procedures attempt to modulate activity in cortical regions that represent nodes in brain circuits believed to be involved in MDD. One challenge in neuromodulation trials has been the difficulty in quantifying outcome variability. We sought to understand the effects of neuromodulation therapies and their sources of variability while adding an objective perspective to assess clinical improvement in neuropsychiatric disorders such as depression. The goal of my dissertation was to investigate the neuronal circuitry of MDD patients who were treated using neuromodulation. Our primary measures were behavior scores and results from functional neuroimaging. The specific aims of this study were to answer three fundamental questions: 1) What is the role of stimulation parameters in patient response to chronic epidural cortical stimulation (EpCS) for MDD? 2) What functional changes result from repetitive transcranial magnetic stimulation (rTMS) for MDD? 3) How does stimulation of different targets in the depressive circuit affect antidepressive response? Our results suggest that combining neuroimaging with computational tools can increase the predictive power to determine who is likely to respond to a specific neuromodulation treatment course. We demonstrated the significance of stimulation parameters (location, polarity, duration) and the engagement of crucial nodes of the depressive circuit in order to achieve a sustained clinical improvement. Additionally, we showed that it is possible to affect deeper brain regions by targeting superficial areas that are easier to access with noninvasive modalities. The approaches highlighted in this dissertation can provide valuable insights about patients evaluated for neuromodulation for depression

Proceedings of the 11th Annual Deep Brain Stimulation Think Tank: pushing the forefront of neuromodulation with functional network mapping, biomarkers for adaptive DBS, bioethical dilemmas, AI-guided neuromodulation, and translational advancements

The Deep Brain Stimulation (DBS) Think Tank XI was held on August 9–11, 2023 in Gainesville, Florida with the theme of “Pushing the Forefront of Neuromodulation”. The keynote speaker was Dr. Nico Dosenbach from Washington University in St. Louis, Missouri. He presented his research recently published in Nature inn a collaboration with Dr. Evan Gordon to identify and characterize the somato-cognitive action network (SCAN), which has redefined the motor homunculus and has led to new hypotheses about the integrative networks underpinning therapeutic DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers, and researchers (from industry and academia) can freely discuss current and emerging DBS technologies, as well as logistical and ethical issues facing the field. The group estimated that globally more than 263,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. This year's meeting was focused on advances in the following areas: cutting-edge translational neuromodulation, cutting-edge physiology, advances in neuromodulation from Europe and Asia, neuroethical dilemmas, artificial intelligence and computational modeling, time scales in DBS for mood disorders, and advances in future neuromodulation devices

Proceedings of the Eighth Annual Deep Brain Stimulation Think Tank: Advances in Optogenetics, Ethical Issues Affecting DBS Research, Neuromodulatory Approaches for Depression, Adaptive Neurostimulation, and Emerging DBS Technologies

We estimate that 208,000 deep brain stimulation (DBS) devices have been implanted to address neurological and neuropsychiatric disorders worldwide. DBS Think Tank presenters pooled data and determined that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. The DBS Think Tank was founded in 2012 providing a space where clinicians, engineers, researchers from industry and academia discuss current and emerging DBS technologies and logistical and ethical issues facing the field. The emphasis is on cutting edge research and collaboration aimed to advance the DBS field. The Eighth Annual DBS Think Tank was held virtually on September 1 and 2, 2020 (Zoom Video Communications) due to restrictions related to the COVID-19 pandemic. The meeting focused on advances in: (1) optogenetics as a tool for comprehending neurobiology of diseases and on optogenetically-inspired DBS, (2) cutting edge of emerging DBS technologies, (3) ethical issues affecting DBS research and access to care, (4) neuromodulatory approaches for depression, (5) advancing novel hardware, software and imaging methodologies, (6) use of neurophysiological signals in adaptive neurostimulation, and (7) use of more advanced technologies to improve DBS clinical outcomes. There were 178 attendees who participated in a DBS Think Tank survey, which revealed the expansion of DBS into several indications such as obesity, post-traumatic stress disorder, addiction and Alzheimer’s disease. This proceedings summarizes the advances discussed at the Eighth Annual DBS Think Tank

Longitudinal Changes in Depressive Circuitry in Response to Neuromodulation Therapy

Major depressive disorder (MDD) is a public health problem worldwide. There is increasing interest in using non-invasive therapies such as repetitive transcranial magnetic stimulation (rTMS) to treat MDD. However, the changes induced by rTMS on neural circuits remain poorly characterized. The present study aims to test whether the brain regions previously targeted by deep brain stimulation (DBS) in the treatment of MDD respond to rTMS, and whether functional connectivity (FC) measures can predict clinical response..

Longitudinal Changes in Depressive Circuitry in Response to Neuromodulation Therapy

Background: Major Depressive Disorder (MDD) is a public health problem worldwide. There is increasing interest in using non-invasive therapies such as repetitive transcranial magnetic stimulation (rTMS) to treat MDD. However, the changes induced by rTMS on neural circuits remain poorly characterized. The present study aims to test whether the brain regions previously targeted by deep brain stimulation (DBS) in the treatment of MDD respond to rTMS, and whether functional connectivity measures can predict clinical response.Methods: rTMS (20 sessions) was administered to five MDD patients at the left-dorsolateral prefrontal cortex (L-DLPFC) over 4 weeks. Magnetoencephalography (MEG) recordings and Montgomery-Asberg Depression Rating Scale (MADRS) assessments were acquired before, during and after treatment. Our primary measures, obtained with MEG source imaging, were changes in power spectral density (PSD) and changes in functional connectivity as measured using coherence.Results: Of the five patients, four met the clinical response criterion (40% or greater decrease in MADRS) after four weeks of treatment. An increase in gamma power at the L-DLPFC was correlated with improvement in symptoms. We also found that increases in delta band connectivity between L-DLPFC/amygdala and L-DLPFC/pregenual anterior cingulate cortex (pACC), and decreases in gamma band connectivity between L-DLPFC/subgenual anterior cingulate cortex (sACC), were correlated with improvements in depressive symptoms. Conclusions: Our results suggest that non-invasive intervention techniques, such as rTMS, modulate the ongoing activity of depressive circuits targeted for DBS, and that MEG can capture these changes. Gamma oscillations may originate from GABA-mediated inhibition, which increases synchronization of large neuronal populations, possibly leading to increased long-range functional connectivity. We postulate that responses to rTMS could provide valuable insights into early evaluation of patient candidates to DBS surgery

The Artificial Pancreas (semester?), IPRO 308

The objective of this IPRO is to develop a system that will function as an artificial pancreas and will incorporate an insulin delivery system with a non invasive glucose monitor.Deliverables for IPRO 308: The Artificial Pancreas for the Fall 2006 semeste