Deep Brain Stimulation Initiative: Toward Innovative Technology, New Disease Indications, and Approaches to Current and Future Clinical Challenges in Neuromodulation Therapy

Abstract

Deep brain stimulation (DBS) is one of the most important clinical therapies for neurological disorders. DBS also has great potential to become a great tool for clinical neuroscience research. Recently, the National Engineering Laboratory for Neuromodulation at Tsinghua University held an international Deep Brain Stimulation Initiative workshop to discuss the cutting-edge technological achievements and clinical applications of DBS. We specifically addressed new clinical approaches and challenges in DBS for movement disorders (Parkinson's disease and dystonia), clinical application toward neurorehabilitation for stroke, and the progress and challenges toward DBS for neuropsychiatric disorders. This review highlighted key developments in (1) neuroimaging, with advancements in 3-Tesla magnetic resonance imaging DBS compatibility for exploration of brain network mechanisms; (2) novel DBS recording capabilities for uncovering disease pathophysiology; and (3) overcoming global healthcare burdens with online-based DBS programming technology for connecting patient communities. The successful event marks a milestone for global collaborative opportunities in clinical development of neuromodulation to treat major neurological disorders.

Keywords: MRI compatibility; deep brain stimulation; depression; gait disability; neuromoxdulation.

Figure 1

Follow-ups of patients with MR-compatible deep brain stimulation (DBS) implanted were successfully completed at 1, 3, 6, and 12 months, with intensive 3T MR scan. High in-plan resolution T2-weighted fast spin echo sequences (T2_TSE_COR and T2_TSE_TRA) and high specific absorption rate (SAR) isotropic sequences (T1_3D, T2_3D, and QSM) were adopted for anatomy analysis. Simultaneous non-contrast angiographies (SNAP) and diffusion tensor imaging (DTI) were taken for monitoring potential lesion on blood vessels and edema occurrence. A special sequence, magnetic resonance thermometry (MRT) used for tissue temperature online assessment. No adverse events were found that related to MRI.

Figure 2

This is an illustration on how deep brain stimulation parameters can be learned and optimized online with feedback. Patient conditions are represented in the State Space. Action Space contains all possible stimulating patterns. The Learning Algorithm learns from domain knowledge and history data, then observes treatment effects (Reward) and optimizes stimulating pattern (Action) online.

Figure 3

Connectivity predicts deep brain stimulation (DBS) outcome in Parkinson's disease (25). (A) Active stimulation coordinates from five cohorts out of two DBS centers mapped to subcortical anatomy [subthalamic nucleus (STN) shown in orange]. (B) Cortical connectivity map predictive of clinical outcome analyzed using normative-connectome based on resting-state functional MRI (rs-fMRI). Hot colors show areas that are associated with good clinical outcome if the electrode is strongly connected to them. In contrast, functional anticorrelation to areas in cold colors is associated with beneficial outcome. (C) Fiber tracts associated with good (red), intermediate (yellow), or poor (blue) clinical outcome. Connectivity profiles shown in (B,C) are able to predict motor improvement in out-of-sample data (across DBS cohorts and centers; R in the range of 0.5; ~20% variance explained).

Figure 4

Subthalamic nucleus stimulation suppresses functional activity in large-scale brain networks, including sensorimotor and association regions in the frontal lobe. The map shows the functional MRI (fMRI) contrast between “DBS on” condition and “DBS off” condition in 11 patients with Parkinson's disease. Functional data were recorded using 3-Tesla MRI when deep brain stimulation (DBS) was turned on (36-s blocks) and off (24-s blocks) using a block design.

Figure 5

Rules ventral prefrontal cortical axons use to reach their targets: implications for diffusion tensor imaging tractography and deep brain stimulation for psychiatric illness (61). Organization of fibers passing through the subgenual cingulate gyrus white matter (SCGwm) (A) and anterior limb of the internal capsule (ALIC) (B). (A) Schematic of an electrode passing through the SCGwm, indicating the cortical fibers involved at each contact. AF, amygdala fugal pathway; CB, cingulate bundle; CC, corpus callosum, EC, external capsule; EMC, extreme capsule; IC, internal capsule; los, lateral orbital sulcus; mos, medial orbital sulcus; olfs, olfactory sulcus; SLF, superior longitudinal fasciculus; UF, uncinate fasciculus. (B) Organization of fibers in the human ALIC. Red, OFC and vmPFC fibers; yellow, ventrolateral PFC fibers; light blue, dACC fibers; green, dorsolateral PFC fibers; blue, dorsomedial PFC fibers.

Figure 6

Prospective targeting of these four white matter bundles can be performed reliably in individual patients, and use of this method improves long-term outcomes. (A) Four-bundle white matter “blueprint”: cingulum (yellow), uncinate fasciculus (blue), forceps minor (red), frontal-striatal (white). (B) Whole-brain tractography loaded in patient-specific stereotactic frame space using StimVision. (C) Visualizing tracts passing through the volume of tissue activated (VTA) to define optimal target location that best visually matched the “blueprint.” (D) Finalization of lead trajectory with the neurosurgeon to avoid cerebral vasculature and choosing the point of entry.

Figure 7

Effects of spinal cord stimulation on postural control in Parkinson's disease patients with freezing of gait (132). On the top left, the figures show the representation of the step initiation task from quiet standing to the actual step, showing the marker on the right malleolus to detect the moment that the foot clears the floor. The graph below shows body weight shifting toward the supporting leg [anticipatory postural adjustment (APA)] during the three different conditions [gray curve, spinal cord stimulation (SCS) OFF; blue curve, 60 Hz-CS; green curve, 300 Hz-SCS]. On the right is a representation of the spinal cord showing the site of stimulation (T2) used in the same report.

Figure 8

(A) Illustration depicting a suboccipital approach to delivering deep brain stimulation therapy to the cerebellar dentate nucleus. (B) Simplified overview of the human dentatothalamocortical (DTC) and corticopontocerebellar (CPC) pathways. The DTC (red) projects through the ipsilateral superior cerebellar peduncle, decussating at the level of the pons, to terminate in contralateral thalamus, where its activity influences widespread thalamocortical interactions. The CPC is shown in green descending from the cortex, decussating in the ipsilateral pons, and terminating in the contralateral cerebellar hemisphere.

Figure 9

Pediatric Deep Brain Stimulation Using Awake Recording and Stimulation for Target Selection in an Inpatient Neuromodulation Monitoring Unit (170). Axial (A,B) and coronal (C,D) MRI showing the position of temporary leads within the basal ganglia and thalamus. Stereotactic planning trajectories are shown in (B,D).