Goyal, Abhinav

Abstract Neurochemical recording techniques have expanded our understanding of the pathophysiology of neurological disorders, as well as the mechanisms of action of treatment modalities like deep brain stimulation (DBS). DBS is used to treat diseases such as Parkinson’s disease, Tourette syndrome, and obsessive-compulsive disorder, among others. Although DBS is effective at alleviating symptoms related to these diseases and improving the quality of life of these patients, the mechanism of action of DBS is currently not fully understood. A leading hypothesis is that DBS modulates the electrical field potential by modifying neuronal firing frequencies to non-pathological rates thus providing therapeutic relief. To address this gap in knowledge, recent advances in electrochemical sensing techniques have given insight into the importance of neurotransmitters, such as dopamine, serotonin, glutamate, and adenosine, in disease pathophysiology. These studies have also highlighted their potential use in tandem with electrophysiology to serve as biomarkers in disease diagnosis and progression monitoring, as well as characterize response to treatment. Here, we provide an overview of disease-relevant neurotransmitters and their roles and implications as biomarkers, as well as innovations to the biosensors used to record these biomarkers. Furthermore, we discuss currently available neurochemical and electrophysiological recording devices, and discuss their viability to be implemented into the development of a closed-loop DBS system.

The thalamic ventral intermediate nucleus (VIM) can be targeted for treatment of tremor by several procedures, including deep brain stimulation (DBS) and, more recently, MR-guided focused ultrasound (MRgFUS). To date, such targeting has relied predominantly on coordinate-based or atlas-based techniques rather than directly targeting the VIM based on imaging features. While general regional differences of features within the thalamus and some related white matter tracts can be distinguished with conventional imaging techniques, internal nuclei such as the VIM are not discretely visualized. Advanced imaging methods such as quantitative susceptibility mapping (QSM) and fast gray matter acquisition T1 inversion recovery (FGATIR) MRI and high-field MRI pulse sequences that improve the ability to image the VIM region are emerging but have not yet been shown to have reliability and accuracy to serve as the primary method of VIM targeting. Currently, the most promising imaging approach to directly identify the VIM region for clinical purposes is MR diffusion tractography. In this review and update, the capabilities and limitations of conventional and emerging advanced methods for evaluation of internal thalamic anatomy are briefly reviewed. The basic principles of tractography most relevant to VIM targeting are provided for familiarization. Next, the key literature to date addressing applications of DTI and tractography for DBS and MRgFUS is summarized, emphasizing use of direct targeting. This literature includes 1-tract (dentatorubrothalamic tract [DRT]), 2-tract (pyramidal and somatosensory), and 3-tract (DRT, pyramidal, and somatosensory) approaches to VIM region localization through tractography. The authors introduce a 3-tract technique used at their institution, illustrating the oblique curved course of the DRT within the inferior thalamus as well as the orientation and relationship of the white matter tracts in the axial plane. The utility of this 3-tract tractography approach to facilitate VIM localization is illustrated with case examples of variable VIM location, targeting superior to the anterior commissure–posterior commissure plane, and treatment in the setting of pathologic derangement of thalamic anatomy. Finally, concepts demonstrated with these case examples and from the prior literature are synthesized to highlight several potential advantages of tractography for VIM region targeting.