Person:

Shih, Ludy

Background: There is increasing interest in the use of non-invasive brain stimulation to characterize and potentially treat essential tremor (ET). Studies have used a variety of stimulation coils, paradigms, and target locations to make these observations. We reviewed the literature to compare prior studies and to evaluate the rationale and the methods used in these studies. Methods: We performed a systematic literature search of the PubMed database using the terms “transcranial,” “noninvasive,” “brain stimulation,” “transcranial magnetic stimulation (TMS),” “transcranial direct current stimulation (tDCS),” “transcranial alternating current stimulation (tACS),” and “essential tremor.” Results: Single pulses of TMS to the primary motor cortex have long been known to reset tremor. Although there are relatively few studies showing alterations in motor cortical physiology, such as motor threshold, short and long intracortical inhibition, and cortical silent period, there may be some evidence of altered intracortical facilitation and cerebello-brain inhibition in ET. Repetitive TMS, theta burst stimulation, tDCS, and tACS have been applied to human subjects with tremor with some preliminary signs of tremor reduction, particularly in those studies that employed consecutive daily sessions. Discussion A variety of stimulation paradigms and targets have been explored, with the increasing rationale an interest in targeting the cerebellum. Rigorous assessment of coil geometry, stimulation paradigm, rationale for selection of the specific anatomic target, and careful phenotypic and physiologic characterization of the subjects with ET undergoing these interventions may be critical in extending these preliminary findings into effective stimulation therapies.

Background: Resting tremor is common in Parkinson’s disease (PD), but up to 47% of PD patients have action tremor, which is sometimes resistant to medications. Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus or subthalamic nucleus (STN) is effective for medication-refractory tremor in PD, though it remains unclear whether STN DBS is as effective as VIM DBS for postural/action tremor related to PD. Methods: We carried out a single-center retrospective review of patients with medication-refractory resting, postural, and action PD tremor, treated with either VIM or STN DBS between August 2004 and March 2014. We assessed the degree of improvement using items 20 and 21 of the Unified Parkinson’s Disease Rating Scale (UPDRS) motor scale and examined the proportion of patients achieving tremor arrest. Results: A total of 18 patients were analyzed, 10 treated with STN and eight treated with VIM, with similar off-medication motor UPDRS scores. There was no significant difference in improvement in tremor scores or in the proportion of patients experiencing tremor arrest between the two stimulation sites. Overall, 56% and 72% of patients experienced complete absence of postural/action tremor and resting tremor, respectively, at last follow-up. Discussion This study demonstrated excellent outcomes on both resting and postural/action tremor after either VIM or STN DBS. Resting tremor improved to a greater degree than postural/action tremor in both groups. These results suggest that a large randomized controlled trial is needed to show a superior effect of one target on PD tremor.

A method for capturing gait signatures in neurological conditions that allows comparison of human gait with animal models would be of great value in translational research. However, the velocity dependence of gait parameters and differences between quadruped and biped gait have made this comparison challenging. Here we present an approach that accounts for changes in velocity during walking and allows for translation across species. In mice, we represented spatial and temporal gait parameters as a function of velocity and established regression models that reproducibly capture the signatures of these relationships during walking. In experimental parkinsonism models, regression curves representing these relationships shifted from baseline, implicating changes in gait signatures, but with marked differences between models. Gait parameters in healthy human subjects followed similar strict velocity dependent relationships which were altered in Parkinson’s patients in ways that resemble some but not all mouse models. This novel approach is suitable to quantify qualitative walking abnormalities related to CNS circuit dysfunction across species, identify appropriate animal models, and it provides important translational opportunities.

The proceedings of the 3rd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, imaging, and computational work on DBS for the treatment of neurological and neuropsychiatric disease. Significant innovations of the past year are emphasized. The Think Tank's contributors represent a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers, and members of industry. Presentations and discussions covered a broad range of topics, including policy and advocacy considerations for the future of DBS, connectomic approaches to DBS targeting, developments in electrophysiology and related strides toward responsive DBS systems, and recent developments in sensor and device technologies.