Opportunities of connectomic neuromodulation

Abstract

The process of altering neural activity – neuromodulation – has long been used to treat patients with brain disorders and answer scientific questions. Deep brain stimulation in particular has provided clinical benefit to over 150,000 patients. However, our understanding of how neuromodulation impacts the brain is evolving. Instead of focusing on the local impact at the stimulation site itself, we are considering the remote impact on brainregions connected to the stimulation site. Brain connectivity information derived from advanced magnetic resonance imaging data can be used to identify these connections and better understand clinical and behavioral effectsof neuromodulation. In this article, we review studies combining neuromodulation and brain connectomics, highlighting opportunities where this approach may prove particularly valuable. We focus on deep brain stimulation, but show that the same principles can be applied to other forms of neuromodulation, such as transcranial magnetic stimulation and MRI-guided focused ultrasound. We outline future perspectives and provide testable hypotheses for future work.

Functional Connectome Prediction of Anxiety Related to the COVID-19 Pandemic

“…The classification analysis confirms the potential clinical relevance of the neuromarkers of pandemic-related anxiety and also highlights the higher susceptibility to mental distress (e.g., pathological anxiety) during the pandemic. The anxiety-specific neuromarkers may provide a special contribution to novel clinical practice for stress and anxiety reduction, such as defining connectome-based targets for neuromodulation (39,40).…”

Effective subthalamic and pallidal deep brain stimulation – are we modulating the same network?

“…Applying normative connectome data to brain stimulation sites in 95 patients from two centers, the study concluded that effective STN-DBS electrodes would modulate a region within the STN that was functionally connected to large portions of the prefrontal cortex, including supplementary motor area (SMA) and inferior frontal cortex (IFC) and functionally anticorrelated with primary motor cortex (M1). Similar studies accumulated evidence that neuromodulation of a specific network may result in clinical responses specific to a certain symptom (for a review see Horn and Fox 6 ). Following this concept of circuitopathies – networks with impact on specific symptoms or behaviors – it might be possible to modulate the same network at different stimulation sites to reach similar changes in clinical or behavioral outcomes.…”

“…Augmenting such an analysis with additional cohorts could one day lead to a personalized DBS targeting the network tailored to the leading symptom in each patient. 6…”

“…Still, use of normative connectomes in context of DBS has led to models that were predictive in out-of-sample datasets. 5,6,8,61-64 Finally, electrode models themselves have inaccuracies that are based on factors such as i) resolution constraints of underlying data, ii) complexity of and small size of subcortical targets and iii) registration errors when aggregating data across patients to make them comparable. 16 To minimize impact of these constraints, we used a specialized DBS imaging pipeline that is based on multispectral normalizations evaluated for both STN and GPi, phantom-validated electrode localizations and careful manual inspection of results in each processing step.…”

Dual-Viral Transduction Utilizing Highly Efficient Retrograde Lentivirus Improves Labeling of Long Propriospinal Neurons

“…Understanding the complexity and specificity of neural pathways and circuits in the mammalian nervous system is a major goal for neuroanatomists and is vital to understand and treat nervous system injuries and disorders (Nassi et al, 2015;Zeng, 2018;Horn and Fox, 2020;Lanciego and Wouterlood, 2020;Ugolini, 2020;Wong et al, 2020). The development and refinement of technologies such as functional near-infrared spectroscopy (Cao et al, 2015;Hu et al, 2020), diffusion weighted magnetic resonance imaging (Jeurissen et al, 2019;Yeh et al, 2020), and resting-state functional magnetic resonance imaging (Fox and Raichle, 2007;Horn and Fox, 2020) have enhanced our understanding of macroscale connectomics, and improved patient treatments and outcomes (Horn et al, 2017;Joutsa et al, 2018;Okromelidze et al, 2020). Mesoscale connectomics-characterizing a single population of neurons and/or connectivity of those neurons-has made similar progress (Lanciego and Wouterlood, 2020;Ugolini, 2020), but traditional tracers such as horseradish peroxidase, cholera toxin subunit B (CTB), hydroxystilbamidine (known commercially as Fluoro-Gold), and conjugated dextran amines [which include biotinylated dextran amine (BDA), and rhodamine conjugated dextran amine (RDA), also known as Fluoro-Ruby (FR) or Mini Ruby depending on molecular weight] remain the most widely used technique.…”