Objective

To determine whether initial presurgical evaluation of deep brain stimulation (DBS) candidacy with video telemedicine (VTEL) can reliably predict surgical candidacy (patients who will eventually undergo DBS surgery) and decrease resource utilization when compared to an in-person evaluation.

Methods

In this retrospective, cohort analysis, all out-of-state referrals to the San Francisco Veterans Affairs from 2008 to 2013 for DBS therapy were reviewed and their surgical outcomes were assessed until 2017. Patients were designated as good, borderline, or poor surgical candidates after initial evaluation, and their rates of undergoing DBS were recorded. An assessment of patient travel costs was performed.

Results

There were 60 out-of-state DBS referrals identified out of the 148 initial presurgical DBS evaluations completed for surgical treatment of dystonia, essential tremor, or Parkinson disease; 24 patients underwent in-person consultation and 36 patients underwent evaluation via VTEL. There was no difference between the rates of undergoing surgical treatment with DBS based on surgical candidacy for patients in the in-person and VTEL cohorts. Patients who underwent initial presurgical screening via VTEL saved time and money.

Conclusions

VTEL can be used to facilitate presurgical screening for DBS and saves costs.

In Parkinson's disease (PD), subthalamic nucleus beta band oscillations are decreased by therapeutic deep-brain stimulation (DBS) and this has been proposed as important to the mechanism of therapy. The globus pallidus is a common alternative target for PD with similar motor benefits as subthalamic DBS, but effects of pallidal stimulation in PD are not well studied, and effects of pallidal DBS on cortical function in PD are unknown. Here, in 20 PD and 14 isolated dystonia human patients of both genders undergoing pallidal DBS lead implantation, we recorded local field potentials from the globus pallidus and in a subset of these, recorded simultaneous sensorimotor cortex ECoG potentials. PD patients had elevated resting pallidal low beta band (13-20 Hz) power compared with dystonia patients, whereas dystonia patients had elevated resting pallidal theta band (4-8 Hz) power compared with PD. We show that this results in disease-specific patterns of interaction between the pallidum and motor cortex: PD patients demonstrated relatively elevated phase coherence with the motor cortex in the beta band and this was reduced by therapeutic pallidal DBS. Dystonia patients had greater theta band phase coherence. Our results support the hypothesis that specific motor phenomenology observed in movement disorders are associated with elevated network oscillations in specific frequency bands, and that DBS in movement disorders acts in general by disrupting elevated synchronization between basal ganglia output and motor cortex.SIGNIFICANCE STATEMENT Perturbations in synchronized oscillatory activity in brain networks are increasingly recognized as important features in movement disorders. The globus pallidus is a commonly used target for deep-brain stimulation (DBS) in Parkinson's disease (PD), however, the effects of pallidal DBS on basal ganglia and cortical oscillations are unknown. Using invasive intraoperative recordings in patients with PD and isolated dystonia, we found disease-specific patterns of elevated oscillatory synchronization within the pallidum and in coherence between pallidum and motor cortex. Therapeutic pallidal DBS in PD suppresses these elevated synchronizations, reducing the influence of diseased basal ganglia on cortical physiology. We propose a general mechanism for DBS therapy in movement disorders: functional disconnection of basal ganglia output and motor cortex by coherence suppression.

In Parkinson's disease (PD), striatal dopamine denervation results in a cascade of abnormalities in the single-unit activity of downstream basal ganglia nuclei that include increased firing rate, altered firing patterns, and increased oscillatory activity. However, the effects of these abnormalities on cortical function are poorly understood. Here, in humans undergoing deep brain stimulator implantation surgery, we use the novel technique of subdural electrocorticography in combination with subthalamic nucleus (STN) single-unit recording to study basal ganglia-cortex interactions at the millisecond time scale. We show that in patients with PD, STN spiking is synchronized with primary motor cortex (M1) local field potentials in two distinct patterns: first, STN spikes are phase-synchronized with M1 rhythms in the theta, alpha, or beta (4-30 Hz) bands. Second, STN spikes are synchronized with M1 gamma activity over a broad spectral range (50-200 Hz). The amplitude of STN spike-synchronized gamma activity in M1 is itself rhythmically modulated by the phase of a lower-frequency rhythm (phase-amplitude coupling), such that "waves" of phase-synchronized gamma activity precede the occurrence of STN spikes. We show the disease specificity of these phenomena in PD, by comparison with STN-M1 paired recordings performed in a group of patients with a different disorder, primary craniocervical dystonia. Our findings support a model of the basal ganglia-thalamocortical loop in PD in which gamma activity in primary motor cortex, modulated by the phase of low-frequency rhythms, drives STN unit discharge.

Objective

Recently, an iMRI-guided technique for implanting DBS electrodes without MER was developed at our center. Here we report the clinical outcomes of PD patients undergoing STN DBS surgery using this surgical approach.

Methods

Consecutive PD patients undergoing bilateral STN DBS using this method were prospectively studied. Severity of PD was determined using the UPDRS scores, Hoehn and Yahr staging score, stand-sit-walk testing, and the dyskinesia rating scale. The primary outcome measure was the change in UPDRS III off medication score at 6 months. DBS stimulation parameters, adverse events, levodopa equivalent daily dose (LEDD), and DBS lead locations were also recorded. Seventeen advanced PD patients (9M/8F) were enrolled from 2007 to 2009.

Results

The mean UPDRS III off medication score improved from 44.5 to 22.5 (49.4%) at 6 months (p=0.001). Other secondary outcome measures (UPDRS II, III on medication, and IV) significantly improved as well (p<0.01). LEDD decreased by an average of 24.7% (p=0.003). Average stimulation parameters were: 2.9V, 66.4μs, 154Hz.

Conclusion

This pilot study demonstrates that STN DBS leads placed using the iMRI-guided method results in significantly improved outcomes in PD symptoms, and these outcomes are similar to what has been reported using traditional frame-based, MER-guided stereotactic methods.

Local field potentials (LFP) recorded from the subthalamic nucleus in patients with Parkinson's disease (PD) demonstrate prominent oscillations in the beta (13-30 Hz) frequency range, and reduction of beta band spectral power by levodopa and deep brain stimulation (DBS) is correlated with motor symptom improvement. Several features of beta activity have been theorized to be specific biomarkers of the parkinsonian state, though these have rarely been studied in non-parkinsonian conditions. To compare resting state LFP features in PD and isolated dystonia and evaluate disease-specific biomarkers, we recorded subthalamic LFPs from 28 akinetic-rigid PD and 12 isolated dystonia patients during awake DBS implantation. Spectral power and phase-amplitude coupling characteristics were analyzed. In 26/28 PD and 11/12 isolated dystonia patients, the LFP power spectrum had a peak in the beta frequency range, with similar amplitudes between groups. Resting state power did not differ between groups in the theta (5-8 Hz), alpha (8-12 Hz), beta (13-30 Hz), broadband gamma (50-200 Hz), or high frequency oscillation (HFO, 250-350 Hz) bands. Analysis of phase-amplitude coupling between low frequency phase and HFO amplitude revealed significant interactions in 19/28 PD and 6/12 dystonia recordings without significant differences in maximal coupling or preferred phase. Two features of subthalamic LFPs that have been proposed as specific parkinsonian biomarkers, beta power and coupling of beta phase to HFO amplitude, were also present in isolated dystonia, including focal dystonias. This casts doubt on the utility of these metrics as disease-specific diagnostic biomarkers.

Deep brain stimulation (DBS) is increasingly applied for the treatment of brain disorders, but its mechanism of action remains unknown. Here we evaluate the effect of basal ganglia DBS on cortical function using invasive cortical recordings in Parkinson's disease (PD) patients undergoing DBS implantation surgery. In the primary motor cortex of PD patients, neuronal population spiking is excessively synchronized to the phase of network oscillations. This manifests in brain surface recordings as exaggerated coupling between the phase of the beta rhythm and the amplitude of broadband activity. We show that acute therapeutic DBS reversibly reduces phase-amplitude interactions over a similar time course as that of the reduction in parkinsonian motor signs. We propose that DBS of the basal ganglia improves cortical function by alleviating excessive beta phase locking of motor cortex neurons.

Background/aims

Nonrechargeable deep brain stimulation implantable pulse generators (IPGs) for movement disorders require surgical replacement every few years due to battery depletion. Rechargeable IPGs reduce frequency of replacement surgeries and inherent risks of complications but require frequent recharging. Here, we evaluate patient experience with rechargeable IPGs and define predictive characteristics for higher satisfaction.

Methods

We contacted all patients implanted with rechargeable IPGs at a single center in a survey-based study. We analyzed patient satisfaction with respect to age, diagnosis, target, charging duration, and body mass index. We tabulated hardware-related adverse events.

Results

Dystonia patients had significantly higher satisfaction than Parkinson's disease patients in recharging, display, programmer, and training domains. Common positive responses were "fewer surgeries" and "small size." Common negative responses were "difficulty finding the right position to recharge" and "need to recharge every day." Hardware-related adverse events occurred in 21 of 59 participants.

Conclusion

Patient experience with rechargeable IPGs was largely positive; however, frustrations with recharging and adverse events were common. Dystonia diagnosis was most predictive of high satisfaction across multiple categories, potentially related to expected long disease duration with need for numerous IPG replacements.

OBJECTIVE Dysfunction of distributed neural networks underlies many brain disorders. The development of neuromodulation therapies depends on a better understanding of these networks. Invasive human brain recordings have a favorable temporal and spatial resolution for the analysis of network phenomena but have generally been limited to acute intraoperative recording or short-term recording through temporarily externalized leads. Here, the authors describe their initial experience with an investigational, first-generation, totally implantable, bidirectional neural interface that allows both continuous therapeutic stimulation and recording of field potentials at multiple sites in a neural network. METHODS Under a physician-sponsored US Food and Drug Administration investigational device exemption, 5 patients with Parkinson's disease were implanted with the Activa PC+S system (Medtronic Inc.). The device was attached to a quadripolar lead placed in the subdural space over motor cortex, for electrocorticography potential recordings, and to a quadripolar lead in the subthalamic nucleus (STN), for both therapeutic stimulation and recording of local field potentials. Recordings from the brain of each patient were performed at multiple time points over a 1-year period. RESULTS There were no serious surgical complications or interruptions in deep brain stimulation therapy. Signals in both the cortex and the STN were relatively stable over time, despite a gradual increase in electrode impedance. Canonical movement-related changes in specific frequency bands in the motor cortex were identified in most but not all recordings. CONCLUSIONS The acquisition of chronic multisite field potentials in humans is feasible. The device performance characteristics described here may inform the design of the next generation of totally implantable neural interfaces. This research tool provides a platform for translating discoveries in brain network dynamics to improved neurostimulation paradigms. Clinical trial registration no.: NCT01934296 (clinicaltrials.gov).

Objective

Essential tremor (ET) is characterized by an action tremor believed to be due to excessive theta-alpha activity in the cerebello-thalamo-cortical system. This study aimed to test the hypothesis that therapeutic thalamic stimulation in patients with ET decreases theta-alpha oscillatory activity in primary motor (M1) and sensory (S1) cortices.

Methods

During surgical treatment of ET in 10 patients, an electrocorticography (ECoG) strip electrode was placed temporarily over the arm region of M1 and S1. Local field potentials (LFP) were recorded at rest, during a tremor-inducing posture, during acute therapeutic thalamic stimulation, and following therapeutic thalamotomy (three patients). Power spectral density (PSD) was calculated using the Fast Fourier Transform.

Results

At rest, alpha activity (8-13Hz) in M1 was significantly decreased during high-frequency stimulation, while theta activity (4-8Hz) decreased in S1. Following thalamotomy, theta and beta (13-30Hz) was increased in M1. Induction of postural tremor reduced M1 theta, alpha and beta activity compared to the resting state.

Conclusions

High-frequency thalamic deep brain stimulation (DBS) significantly reduces alpha oscillatory activity in the primary motor cortex of patients with ET, though this change is probably not critical for therapeutic efficacy.

Significance

We demonstrate that ECoG can be effectively used to study the effect of subcortical stimulation on cortical oscillations.

An important mechanism for large-scale interactions between cortical areas involves coupling between the phase and the amplitude of different brain rhythms. Could basal ganglia disease disrupt this mechanism? We answered this question by analysis of local field potentials recorded from the primary motor cortex (M1) arm area in patients undergoing neurosurgery. In Parkinson disease, coupling between β-phase (13-30 Hz) and γ-amplitude (50-200 Hz) in M1 is exaggerated compared with patients with craniocervical dystonia and humans without a movement disorder. Excessive coupling may be reduced by therapeutic subthalamic nucleus stimulation. Peaks in M1 γ-amplitude are coupled to, and precede, the subthalamic nucleus β-trough. The results prompt a model of the basal ganglia-cortical circuit in Parkinson disease incorporating phase-amplitude interactions and abnormal corticosubthalamic feedback and suggest that M1 local field potentials could be used as a control signal for automated programming of basal ganglia stimulators.