Intraoperative vs. Postoperative Side-Effects-Thresholds During Pallidal and Thalamic DBS

Background: It is currently unknown whether results from intraoperative test stimulation of two types of Deep Brain Stimulation (DBS), either during awake pallidal (GPi) or thalamic (Vim), are comparable to the results generated by chronic stimulation through the definitive lead.Objective: To determine whether side-effects-thresholds from intraoperative test stimulation are indicative of postoperative stimulation findings.Methods: Records of consecutive patients who received GPi or Vim were analyzed. Thresholds for the induction of either capsular or non-capsular side-effects were compared at matched depths and at group-level.Results: Records of fifty-two patients were analyzed (20 GPis, 75 Vims). The induction of side-effects was not significantly different between intraoperative and postoperative assessments at matched depths, although a large variability was observed (capsular: GPi DBS: p = 0.79; Vim DBS: p = 0.68); non-capsular: GPi DBS: p = 0.20; and Vim DBS: p = 0.35). Linear mixed-effect models revealed no differences between intraoperative and postoperative assessments, although the Vim had significantly lower thresholds (capsular side-effects p = 0.01, non-capsular side-effects p < 0.01). Unpaired survival analyses demonstrated lower intraoperative than postoperative thresholds for capsular side-effects in patients under GPi DBS (p = 0.01), while higher intraoperative thresholds for non-capsular side-effects in patients under Vim DBS (p = 0.01).Conclusion: There were no significant differences between intraoperative and postoperative assessments of GPi and Vim DBS, although thresholds cannot be directly extrapolated at an individual level due to high variability.

Effects of Chewing Gum Stimuli on General and Emotional Stroop Test

The aim of this study was to determine whether chewing gum affects cognitive function and stress relief. Sixty volunteers (mean age 23.3±3.01 years) without general or neuropsychiatric disease were recruited, and Stroop tests and stress surveys were conducted. Volunteers were administered performed a General and Emotional Stroop test with and without chewing gum, and the response time was recorded. The response time after chewing gum was significantly faster while conducting the General Stroop test. Stimulation of chewing gum may increase blood flow to the brain, which results in increased cognitive function. The response time was longer in the incongruent stimuli test compared to the congruent stimuli test, due to the effect of Stroop interference. However, when the chewing gum stimulus was introduced, the possibility of effectively reducing this effect. Stress index and response time of negative stimuli test showed weak positive correlation. This study suggests that chewing gum may play a positive role in increasing cognitive function and relieving stress.

Centromedian–Parafascicular and Somatosensory Thalamic Deep Brain Stimulation for Treatment of Chronic Neuropathic Pain: A Contemporary Series of 40 Patients

Introduction: The treatment of neuropathic and central pain still remains a major challenge. Thalamic deep brain stimulation (DBS) involving various target structures is a therapeutic option which has received increased re-interest. Beneficial results have been reported in several more recent smaller studies, however, there is a lack of prospective studies on larger series providing long term outcomes. Methods: Forty patients with refractory neuropathic and central pain syndromes underwent stereotactic bifocal implantation of DBS electrodes in the centromedian–parafascicular (CM–Pf) and the ventroposterolateral (VPL) or ventroposteromedial (VPM) nucleus contralateral to the side of pain. Electrodes were externalized for test stimulation for several days. Outcome was assessed with five specific VAS pain scores (maximum, minimum, average pain, pain at presentation, allodynia). Results: The mean age at surgery was 53.5 years, and the mean duration of pain was 8.2 years. During test stimulation significant reductions of all five pain scores was achieved with either CM–Pf or VPL/VPM stimulation. Pacemakers were implanted in 33/40 patients for chronic stimulation for whom a mean follow-up of 62.8 months (range 3–180 months) was available. Of these, 18 patients had a follow-up beyond four years. Hardware related complications requiring secondary surgeries occurred in 11/33 patients. The VAS maximum pain score was improved by ≥50% in 8/18, and by ≥30% in 11/18 on long term follow-up beyond four years, and the VAS average pain score by ≥50% in 10/18, and by ≥30% in 16/18. On a group level, changes in pain scores remained statistically significant over time, however, there was no difference when comparing the efficacy of CM–Pf versus VPL/VPM stimulation. The best results were achieved in patients with facial pain, poststroke/central pain (except thalamic pain), or brachial plexus injury, while patients with thalamic lesions had the least benefit. Conclusion: Thalamic DBS is a useful treatment option in selected patients with severe and medically refractory pain.

Addiction History Moderates the Effect of Prefrontal 10Hz Transcranial Alternating Current Stimulation on Habitual Action Selection

Individuals with substance use disorders (SUDs) transition more quickly from goal-directed to habitual action-selection, but the neural mechanisms underlying this phenomenon remain unclear. Data from animal models suggest that drugs of abuse can modify the neurocircuits that regulate action-selection, enhancing circuits that drive inflexible, habit-based stimulus-response (S-R) action-selection, and weakening circuits that drive flexible, goal-directed actions. Here we tested the effect of bilateral 10 Hz transcranial alternating current stimulation (10Hz-tACs) of the dorsolateral prefrontal cortex on action-selection in men and women with a SUD history and an age- and gender-matched control group. We tested the hypothesis that true 10Hz-tACS versus active sham stimulation would reduce perseverative errors after changed response contingencies for well-learned S-R associations, reflecting reduced habit-based action-selection, specifically in the SUD group (McKim et al. 2016). We found that 10Hz-tACS increased perseverative errors in the control group, but in the SUD group, 10Hz-tACS effects on perseverative errors depended on substance abuse duration: a longer addiction history was associated with a greater reduction of perseverative errors. These results suggest that 10Hz-tACs altered circuit level dynamics regulating behavioral flexibility, and provide a foundation for future studies to test stimulation site, frequency, and timing specificity. Moreover, these data suggest that chronic substance abuse is associated with altered circuit dynamics that are ameliorated by 10Hz-tACs. Determining the generalizability of these effects and their duration merits investigation as a direction for novel therapeutic interventions. These findings are timely based on growing interest in transcranial stimulation methods for treating SUDs (Ekhtiari et al. 2019).

Selecting the Most Effective DBS Contact in Essential Tremor Patients Based on Individual Tractography

Postoperative choice of the most effective deep brain stimulation (DBS) contact in patients with essential tremor (ET) so far relies on lengthy clinical testing. Previous studies showed that the postoperative effectiveness of DBS contacts depends on the distance to the dentatorubrothalamic tract (DRTT). Here, we investigated whether the most effective DBS contact could be determined from calculating stimulation overlap with the individual DRTT. Seven ET patients with bilateral thalamic deep brain stimulation were included retrospectively. Tremor control was assessed for each contact during test stimulation with 2mA. Individual DRTTs were identified from diffusion tensor imaging and contacts were ranked by their stimulation overlap with the respective DRTT in relation to their clinical effectiveness. A linear mixed-effects model was calculated to determine the influence of the DRTT overlap on tremor control. In 92.9% of investigated DBS leads, the contact with the best clinical effect was the contact with the highest or second-highest DRTT-overlap. At the group level, the DRTT-overlap explained 26.7% of the variance in the clinical outcomes (p < 0.001). Our data suggest that the overlap with the DRTT based on individual tractography may serve as a marker to determine the most effective DBS contact in ET patients and reduce burdensome clinical testing in the future.

The role of intraoperative microelectrode recording and stimulation in subthalamic lead placement for Parkinson’s disease

Objective Intraoperative microelectrode recording (MER) and test-stimulation are regarded as the gold standard for proper placement of subthalamic (STN) deep brain stimulation (DBS) electrodes in Parkinson’s disease (PD), requiring the patient to be awake during the procedure. In accordance with good clinical practice, most attending neurologists will request the clinically most efficacious trajectory for definite lead placement. However, the necessity of microelectrode-test-stimulation is disputed, as it may limit the access to DBS therapy, excluding those not willing or incapable of undergoing awake surgery. Methods We retrospectively analyzed the MERs and microelectrode-test-stimulation results with regard to the decision on definite lead placement and clinical outcome in a cohort of 67 PD-patients with STN-DBS. All patients received bilateral quadripolar ring electrodes. To ascertain overall procedural efficacy, we calculated the surgical index (SI) by comparing preoperative motor improvement induced by levodopa to that induced by stimulation 7 to 18 months after surgery, measured as the relative difference between ON and OFF-states on the Unified Parkinson’s Disease Rating Scale motor part (UPDRS-3). Additionally, a side-specific surgical index (SSSI) was calculated using the unilateral assessable items of the UPDRS-3. The SSSI where microelectrode-test-stimulation overruled MER were compared to those where the result of microelectrode-test-stimulation was congruent to MER results. Results A total of 134 electrodes were analyzed. For final lead placement, the central trajectory was chosen in 54% of patient hemispheres. The mean SI was 0.99 (± 0.24). SSSI averaged 1.04 (± 0.45). In 37 lead placements, microelectrode-test-stimulation overruled MER in the final trajectory selection, in 27 of these lead placements adverse effects during microelectrode-test-stimulation were decisive. Neither the number of test electrodes used nor the STN-signal length had an impact on the SSSI. The SSSI did not differ between lead placements with MER/microelectrode-test-stimulation congruency and those where the results of microelectrode-test-stimulation initiated lead placement in a trajectory with shorter STN signal. Conclusion Intraoperative testing is mandatory to ensure an optimal motor outcome of STN DBS in PD-patients when using quadripolar ring electrodes. However, we also demonstrated that neither the length of the STN-signal on MER nor the number of test electrodes influenced the motor outcome.

Selecting the most effective DBS contact in essential tremor patients based on individual tractography

Postoperative choice of the most effective DBS contact in patients with essential tremor (ET) so far relies on lengthy clinical testing. It has been shown that the postoperative effectiveness of DBS contacts depends on the distance to the dentatorubrothalamic tract (DRTT). Here, we investigated whether the most effective DBS contact could be determined from the stimulation overlap with the individual DRTT. Seven ET patients with bilateral thalamic deep brain stimulation were included retrospectively. Tremor control was assessed contact-wise during test stimulation with 2mA. The individual DRTTs were identified from diffusion tensor imaging. Contacts were ranked by their overlap of the test stimulation with the respective DRTT in relation to their clinical effectiveness. A linear mixed-effects model was calculated to determine the influence of the DRTT-overlap on tremor control. In 92.9 % of the cases, the contact with the best clinical effect was the contact with the highest or second-highest DRTT-overlap. On the group level, the DRTT-overlap explained 26.7% of the variance of the clinical outcome (p<0.001). To conclude, data suggest that the overlap with the DRTT based on individual tractography may serve as a marker to determine the most effective DBS contact in ET patients and reduce burdensome clinical testing in the future.

O-Arm Navigated Frameless and Fiducial-Less Deep Brain Stimulation

Object: Deep brain stimulation (DBS) is a very useful procedure for the treatment of idiopathic Parkinson’s disease (PD), essential tremor, and dystonia. The authors evaluated the accuracy of the new method used in their center for the placing of DBS electrodes. Electrodes are placed using the intraoperative O-arm™ (Medtronic)-controlled frameless and fiducial-less system, Nexframe™ (Medtronic). Accuracy was evaluated prospectively in eleven consecutive PD patients (22 electrodes). Methods: Eleven adult patients with PD were implanted using the Nexframe system without fiducials and with the intraoperative O-arm (Medtronic) system and StealthStation™ S8 navigation (Medtronic). The implantation of DBS leads was performed using multiple-cell microelectrode recording, and intraoperative test stimulation to determine thresholds for stimulation-induced adverse effects. The accuracy was checked in three different steps: (1) using the intraoperative O-arm image and its fusion with preoperative planning, (2) using multiple-cell microelectrode recording and counting the number of microelectrodes with the signal of the subthalamic nucleus (STN) and finally, (3) total error was calculated according to a postoperative CT control image fused to preoperative planning. Results: The total error of the procedure was 1.79 mm; the radial error and the vector error were 171 mm and 163 mm. Conclusions: Implantation of DBS electrodes using an O-arm navigated frameless and fiducial-less system is a very useful and technically feasible procedure with excellent patient toleration with experienced Nexframe users. The accuracy of the method was confirmed at all three steps, and it is comparable to other published results.

Activation of the Supplementary Motor Areas Enhances Spinal Reciprocal Inhibition in Healthy Individuals

The supplementary motor area (SMA) may modulate spinal reciprocal inhibition (RI) because the descending input from the SMA is coupled to interneurons in the spinal cord via the reticulospinal tract. Our study aimed to verify whether the anodal transcranial direct current stimulation (anodal-tDCS) of the SMA enhances RI. Two tDCS conditions were used: the anodal stimulation (anodal-tDCS) and sham stimulation (sham-tDCS) conditions. To measure RI, there were two conditions: one with the test stimulus (alone) and the other with the conditioning-test stimulation intervals (CTIs), including 2 ms and 20 ms. RI was calculated at multiple time points: before the tDCS intervention (Pre); at 5 (Int 5) and 10 min; and immediately after (Post 0); and at 5, 10 (Post 10), 15, and 20 min after the intervention. In anodal-tDCS, the amplitude values of H-reflex were significantly reduced for a CTI of 2 ms at Int 5 to Post 0, and a CTI of 20 ms at Int 5 to Pot 10 compared with Pre. Stimulation of the SMA with anodal-tDCS for 15 min activated inhibitory interneurons in RIs by descending input from the reticulospinal tract via cortico–reticulospinal projections. The results showed that 15 min of anodal-tDCS in the SMA enhanced and sustained RI in healthy individuals.

Deactivation of One Subthalamic Nucleus Deep Brain Stimulation Device to Address Brittle Ipsilateral Dyskinesia in a Patient With Tremor-Dominant Parkinson Disease

A 78-year-old right-handed woman with a 10-year history of tremor-dominant Parkinson disease (PD) was recommended for bilateral deep brain stimulation (DBS) in the subthalamic nucleus (STN). The patient was implanted with bilateral omnidirectional STN DBS electrodes after intraoperative microelectrode recordings and intraoperative test stimulation. Immediately after implantation, the motor symptoms improved considerably, but 3 to 4 weeks later, a debilitating left-sided resting tremor re-emerged. Personalized programming at the right STN ameliorated the tremor, while painful dyskinesia and hemiballism of the ipsilateral right side of the body developed subsequently over the next few days. Adapting the stimulation parameters and the dopaminergic medication improved these symptoms only marginally. After turning off the left STN electrode, the dyskinesia and hemiballism disappeared completely. In the following weeks, the amperage of the right STN electrode was increased gradually to control the left-sided resting tremor. This was possible without the development of ipsilateral hyperkinesia. During the off phases of stimulation, a considerable direct improvement of hyperkinesia was noted, and the decision to turn off the left STN electrode was ultimately made.