Temporally optimized patterned stimulation (TOPS®) as a therapy to personalize deep brain stimulation treatment of Parkinson's disease.

Deep brain stimulation (DBS) is a well-established therapy for the motor symptoms of Parkinson's disease (PD), but there remains an opportunity to improve symptom relief. The temporal pattern of stimulation is a new parameter to consider in DBS therapy, and we compared the effectiveness of Temporally Optimized Patterned Stimulation (TOPS) to standard DBS at reducing the motor symptoms of PD. Twenty-six subjects with DBS for PD received three different patterns of stimulation (two TOPS and standard) while on medication and using stimulation parameters optimized for standard DBS.

Stimulus features underlying reduced tremor suppression with temporally patterned deep brain stimulation.

Deep brain stimulation (DBS) provides dramatic tremor relief when delivered at high-stimulation frequencies (more than ∼100 Hz), but its mechanisms of action are not well-understood. Previous studies indicate that high-frequency stimulation is less effective when the stimulation train is temporally irregular. The purpose of this study was to determine the specific characteristics of temporally irregular stimulus trains that reduce their effectiveness: long pauses, bursts, or irregularity per se.

Tremor reduction and modeled neural activity during cycling thalamic deep brain stimulation.

Objective: The effectiveness of deep brain stimulation (DBS) depends on both the frequency and the temporal pattern of stimulation. We quantified responses to cycling DBS with constant frequency to determine if there was a critical on and/or off time for alleviating tremor.

Methods: We measured postural tremor in 10 subjects with thalamic DBS and quantified neuronal entropy in a network model of Vim thalamic DBS.

Deep brain stimulation alleviates parkinsonian bradykinesia by regularizing pallidal activity.

Deep brain stimulation (DBS) of the basal ganglia can alleviate the motor symptoms of Parkinson's disease although the therapeutic mechanisms are unclear. We hypothesize that DBS relieves symptoms by minimizing pathologically disordered neuronal activity in the basal ganglia. In human participants with parkinsonism and clinically effective deep brain leads, regular (i.

Myoclonus and tremor response to thalamic deep brain stimulation parameters in a patient with inherited myoclonus-dystonia syndrome.

We present a 74-year-old woman with inherited myoclonus-dystonia, with predominant myoclonus and a novel mutation in the epsilon-sarcoglycan gene. The patient reports a life-long history of rapid, jerking movements, most severe in the upper extremities as well as a postural and action tremor. Bilateral deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus was performed, and the patient demonstrated moderate clinical improvement in myoclonus.

A model predicting optimal parameters for deep brain stimulation in essential tremor.

In nine patients with essential tremor (14 thalami), the authors varied frequency, voltage, and pulsewidth of thalamic deep brain stimulation, and quantified postural tremor. Low frequency stimulation aggravated tremor; the effect increased with increasing voltage. High frequency stimulation had a U-shaped relation to voltage, with minimum tremor at an optimal voltage characteristic of the individual thalamus and increases in voltage beyond the optimum reduced tremor suppression.

A method to estimate the spatial extent of activation in thalamic deep brain stimulation.

Objective: The goal of this study was to develop, evaluate, and apply a method to quantify the unknown spatial extent of activation in deep brain stimulation (DBS) of the ventral intermedius nucleus (Vim) of the thalamus.

Methods: The amplitude-distance relationship and the threshold amplitudes to elicit clinical responses were combined to estimate the unknown amplitude-distance constant and the distance between the electrode and the border between the Vim and the ventrocaudal nucleus (Vc) of the thalamus. We tested the sensitivity of the method to errors in the input parameters, and subsequently applied the method to estimate the amplitude-distance constant from clinically-measured threshold amplitudes.

Tremor varies as a function of the temporal regularity of deep brain stimulation.

The frequency of stimulation is one of the primary factors determining the effectiveness of deep brain stimulation (DBS) in relieving tremor. DBS efficacy, however, may depend not only on the average frequency of stimulation, but also on the temporal pattern of stimulation. We conducted intraoperative measurements of the effect of temporally irregular DBS (nonconstant interpulse intervals) on tremor.

Amplitude- and frequency-dependent changes in neuronal regularity parallel changes in tremor With thalamic deep brain stimulation.

The mechanisms by which deep brain stimulation (DBS) alleviates tremor remain unclear, but successful treatment can be achieved with properly selected frequency and amplitude. The clinical tremor response to thalamic DBS for essential tremor is dependent on the stimulation frequency and amplitude, and for high frequencies (> or = 90 Hz), increasing amplitude suppressed tremor, whereas for low frequencies (< 60 Hz), increasing amplitude aggravated tremor. We studied the effects of stimulation frequency and amplitude on the output of a population of intrinsically active model neurons to test the hypothesis that regularization of neuronal firing patterns is responsible for the clinical effectiveness of DBS.

Clinical response to varying the stimulus parameters in deep brain stimulation for essential tremor.

Deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus for essential tremor is sometimes limited by side effects. The mechanisms by which DBS alleviates tremor or causes side effects are unclear; thus, it is difficult to select stimulus parameters that maximize the width of the therapeutic window. The goal of this study was to quantify the impact on side effect intensity (SE), tremor amplitude, and the therapeutic window of varying stimulus parameters.

Selection of stimulus parameters for deep brain stimulation.

Objective: To provide an analysis of stimulation parameters for deep brain stimulation (DBS).

Methods: Synthesis of theoretical and empirical findings is used to provide guidance for the selection of stimulus parameters. Finite element modeling is used to investigate the effects of contact location and electrode geometry on the electric field, and to estimate the effects of current density distribution on the limit for non-damaging stimulation.