Functional neuronal activity and connectivity within the subthalamic nucleus in Parkinson’s disease

ObjectiveCharacterization of the functional neuronal activity and connectivity within the subthalamic nucleus (STN) in patients with Parkinson’s disease (PD).MethodsSingle units were extracted from micro-electrode recording (MER) of 18 PD patients who underwent STN deep brain stimulation (DBS) surgery. The firing rate and pattern of simultaneously recorded spike trains and their coherence were analyzed. To provide a precise functional assignment of position to the observed activities, for each patient we mapped its classified multichannel STN MERs to a generic atlas representation with a sensorimotor part and a remaining part.ResultsWithin the sensorimotor part we found significantly higher mean firing rate (P < 0.05) and significantly more burst-like activity (P < 0.05) than within the remaining part. The proportion of significant coherence in the beta band (13–30 Hz) is significantly higher in the sensorimotor part of the STN than elsewhere (P =  0.015).ConclusionsThe STN sensorimotor part distinguishes itself from the remaining part with respect to beta coherence, firing rate and burst-like activity and postoperatively was found as the preferred target area.SignificanceOur firing behavior analysis may help to discriminate the STN sensorimotor part for the placement of the DBS electrode.     

Anterior lead location predicts verbal fluency decline following STN-DBS in Parkinson's disease

IntroductionVerbal fluency (VF) decline is a well-documented cognitive effect of Deep Brain Stimulation of the subthalamic nucleus (STN-DBS) in patients with Parkinson's disease (PD). This decline may be associated with disruption to left-sided frontostriatal circuitry involving the anteroventral non-motor area of the STN. While recent studies have examined the impact of lead location in relation to functional STN subdivisions on VF outcomes, results have been mixed and methods have been limited by atlas-based location mapping.MethodsParticipants included 59 individuals with PD who underwent bilateral STN-DBS. Each participant's active contact location was determined in an atlas-independent fashion, relative to their individual MR-visualized STN midpoint. Multiple linear regression was used to examine lead location in each direction as a predictor of phonemic and semantic VF decline, controlling for demographic and disease variables.ResultsMore anterior lead locations relative to the STN midpoint in the left hemisphere predicted greater phonemic VF decline (B = −2.34, B SE = 1.08, β = −0.29, sr² = 0.08). Lead location was not a significant predictor of semantic VF decline.ConclusionUsing an individualized atlas-independent approach, present findings suggest that more anterior stimulation of the left STN may uniquely contribute to post-DBS VF decline. This is consistent with models in which the anterior STN represents a “non-motor” functional subdivision with connections to frontal regions, e.g., the left dorsal prefrontal cortex. Future studies should investigate the effect of DBS lead trajectory on VF outcomes.     

Localization of motor and verbal fluency effects in subthalamic DBS for Parkinson's disease

IntroductionSubthalamic nucleus deep brain stimulation (STN DBS) improves cardinal motor symptoms of Parkinson's disease (PD) but can worsen verbal fluency (VF). An optimal site of stimulation for overall motor improvement has been previously identified using an atlas-independent, fully individualized, field-modeling approach. This study examines if cardinal motor components (bradykinesia, tremor, and rigidity) share this identified optimal improvement site and if there is co-localization with a site that worsens VF.MethodsAn atlas-independent, field-modeling approach was used to identify sites of maximal STN DBS effect on overall and cardinal motor symptoms and VF in 60 patients. Anatomic coordinates were referenced to the STN midpoint. Symptom severity was assessed with the MDS-UPDRS part III and established VF scales.ResultsSites for improved bradykinesia and rigidity co-localized with each other and the overall part III site (0.09 mm lateral, 0.93 mm posterior, 1.75 mm dorsal). The optimal site for tremor was posterior to this site (0.10 mm lateral, 1.40 mm posterior, 1.93 mm dorsal). Semantic and phonemic VF sites were indistinguishable and co-localized medial to the motor sites (0.32 mm medial, 1.18 mm posterior, 1.74 mm dorsal).ConclusionThis study identifies statistically distinct, maximally effective stimulation sites for tremor improvement, VF worsening, and overall and other cardinal motor improvements in STN DBS. Current electrode sizes and voltage settings stimulate all of these sites simultaneously. However, future targeted lead placement and focused directional stimulation may avoid VF worsening while maintaining motor improvements in STN DBS.     

The effect of dexmedetomidine on the firing properties of STN neurons in Parkinson's disease

Dexmedetomidine (an alpha‐2 adrenergic agonist) sedation is commonly used during subthalamic nucleus (STN) deep‐brain stimulation (DBS). Its effects on the electrophysiological characteristics of human STN neurons are largely unknown. We hypothesised that dexmedetomidine modulates the firing rates and bursting of human STN neurons. We analysed microelectrode recording (MER) data from patients with Parkinson's disease who underwent STN DBS. A ‘Dex bolus’ group (dexmedetomidine bolus prior to MER; 27 cells from seven patients) was compared with a ‘no sedation’ group (29 cells from 11 patients). We also performed within‐patient comparisons with varying dexmedetomidine states. Cells were classified as dorsal half or ventral half based on their relative location in the STN. Neuronal burst and oscillation characteristics were analysed using the Kaneoke–Vitek methodology and local field potential (LFP) oscillatory activity was also investigated. Dexmedetomidine was associated with a slight increase in firing rate (41.1 ± 9.9 vs. 34.5 ± 10.6 Hz, P = 0.02) but a significant decrease in burstiness (number of bursts, P = 0.02; burst index, P < 0.001; percentage of spikes in burst, P = 0.002) of dorsal but not ventral STN neurons. This was not associated with modulation of beta oscillations in the spike‐oscillations analysis(beta peak, P = 0.4; signal‐to‐noise ratio in the beta range for spikes and bursts, P = 0.3 and P = 0.5, respectively) and LFP analysis (Beta power, P = 0.17). As bursting pattern is often used to identify STN and guide electrode placement, we recommend that high‐dose dexmedetomidine should be avoided during DBS surgery.     

Flexible vs. standard subthalamic stimulation in Parkinson disease: A double-blind proof-of-concept cross-over trial

BackgroundDeep brain stimulation (DBS) of the subthalamus (STN) is effective for the treatment of cardinal motor signs of Parkinson disease (PD). Structures around the STN can suppress dyskinesia and tremor (zona incerta) and improve gait and balance (substantia nigra pars reticulata).ObjectiveIs the newer 8-contact linear lead connected to a ‘flexible’ DBS system superior to standard 4-contact stimulation in PD patients receiving STN DBS?MethodsAfter 3 months of open label programming, 10 patients were randomized to standard or flexible stimulation before crossing over to the other arm (3 months each period). Patients and assessors were blinded.ResultsA trend to improvement in Patient Global Impression of Change scores was seen with standard to flexible stimulation and worsening from flexible to standard stimulation (mean ± SD: 0.7 ± 1.2 and −0.4 ± 1.5 respectively, p = 0.152). There was a significant reduction in the number of troublesome symptoms reported prior to DBS (2.6 ± 3.3 per patient), more so with flexible stimulation (0.4 ± 0.6 vs. 1.5 ± 1.6 with standard stimulation, p = 0.001 and p = 0.034). There was no significant difference between the flexible and standard stimulation groups.ConclusionFurther studies confirming that flexible stimulation is superior to standard DBS are warranted.     

Electrophysiologic Evidence That Directional Deep Brain Stimulation Activates Distinct Neural Circuits in Patients With Parkinson Disease

ObjectivesDeep brain stimulation (DBS) delivered via multicontact leads implanted in the basal ganglia is an established therapy to treat Parkinson disease (PD). However, the different neural circuits that can be modulated through stimulation on different DBS contacts are poorly understood. Evidence shows that electrically stimulating the subthalamic nucleus (STN) causes a therapeutic effect through antidromic activation of the hyperdirect pathway—a monosynaptic connection from the cortex to the STN. Recent studies suggest that stimulating the substantia nigra pars reticulata (SNr) may improve gait. The advent of directional DBS leads now provides a spatially precise means to probe these neural circuits and better understand how DBS affects distinct neural networks.Materials and MethodsWe measured cortical evoked potentials (EPs) using electroencephalography (EEG) in response to low-frequency DBS using the different directional DBS contacts in eight patients with PD.ResultsA short-latency EP at 3 milliseconds originating from the primary motor cortex appeared largest in amplitude when stimulating DBS contacts closest to the dorsolateral STN (p < 0.001). A long-latency EP at 10 milliseconds originating from the premotor cortex appeared strongest for DBS contacts closest to the SNr (p < 0.0001).ConclusionsOur results show that at the individual patient level, electrical stimulation of different nuclei produces distinct EP signatures. Our approach could be used to identify the functional location of each DBS contact and thus help patient-specific DBS programming.Clinical Trial RegistrationThe ClinicalTrials.gov registration number for the study is NCT04658641.     

Utilizing 7-Tesla Subthalamic Nucleus Connectivity in Deep Brain Stimulation for Parkinson Disease

BackgroundDeep brain stimulation (DBS) of the subthalamic nucleus (STN) is a highly effective surgical treatment for patients with advanced Parkinson disease (PD). Combining 7.0-Tesla (7T) T2- and diffusion-weighted imaging (DWI) sequences allows for selective segmenting of the motor part of the STN and, thus, for possible optimization of DBS.Materials and Methods7T T2 and DWI sequences were obtained, and probabilistic segmentation of motor, associative, and limbic STN segments was performed. Left- and right-sided motor outcome (Movement Disorders Society Unified Parkinson’s Disease Rating Scale) scores were used for evaluating the correspondence between the active electrode contacts in selectively segmented STN and the clinical DBS effect. The Bejjani line was reviewed for crossing of segments.ResultsA total of 50 STNs were segmented in 25 patients and proved highly feasible. Although the highest density of motor connections was situated in the dorsolateral STN for all patients, the exact partitioning of segments differed considerably. For all the active electrode contacts situated within the predominantly motor-connected segment of the STN, the average hemi-body Unified Parkinson’s Disease Rating Scale motor improvement was 80%; outside this segment, it was 52% (p < 0.01). The Bejjani line was situated in the motor segment for 32 STNs.ConclusionThe implementation of 7T T2 and DWI segmentation of the STN in DBS for PD is feasible and offers insight into the location of the motor segment. Segmentation-guided electrode placement is likely to further improve motor response in DBS for PD. However, commercially available DBS software for postprocessing imaging would greatly facilitate widespread implementation.     

Sleep parameters associated with long-term outcome following subthalamic deep brain stimulation in Parkinson's disease

IntroductionWe aimed to investigate the effects of changes in sleep architecture on long-term clinical outcome in patients with Parkinson's disease (PD) who underwent deep brain stimulation of subthalamic nuclei (STN DBS).MethodsWe followed up eight PD patients before and three years after STN DBS surgery. In addition to clinical assessments, polysomnography (PSG) followed by multiple sleep latency tests was performed before and after STN DBS, while stimulator was ON and OFF.ResultsSubjective sleep latency was significantly decreased (P = 0.033) and sleep duration was increased (P = 0.041), as measured by Pittsburgh sleep quality index. Latency to REM sleep stage was shortened after surgery with STN DBS ON (P = 0.002). Index of central type of abnormal respiratory events was significantly increased while stimulator was ON (P = 0.034). Total number of major body movements was found to be increased when stimulator was turned OFF (P = 0.012). Among PSG data obtained during STN DBS ON, it was observed that duration of N3 sleep was negatively correlated with UPDRS scores at 1st (P = 0.038) and 3rd (P = 0.045) post-operative years. Among PSG variables during STN DBS OFF, durations of N3 sleep (P = 0.017) and REM sleep (P = 0.041) were negatively correlated with UPDRS scores at post-operative 1st year.ConclusionDisturbances in sleep architecture are associated with higher UPDRS scores and worse prognosis at 1st and 3rd post-operative years. Similar results obtained while stimulator was OFF at the end of 1st year support the presence of microlesion effect after STN DBS, which is probably not long lasting.     

Risks of intracranial hemorrhage in patients with Parkinson's disease receiving deep brain stimulation and ablation

ObjectivesThis study analyzed risk factors for hemorrhage in a large series of deep brain stimulation (DBS) and ablation procedures in patients with advanced Parkinson's disease (PD).MethodsSix hundred and forty four subjects with advanced PD treated with DBS or ablation procedures between March 1999 and December 2007 were enrolled in the study. Procedures were performed by the same surgeon, and included DBS in 126 patients, ablation in 507 patients and DBS after prior unilateral ablation procedures in 11 patients. Of 796 target procedures, 207 were DBS including 202 subthalamic nucleus (STN) targets, 3 ventralis intermedius nucleus (Vim) targets and 2 globus pallidus internus (GPi) targets, and the others were 589 ablation procedures including 474 GPi targets and 115 Vim targets. Postoperative CT or MRI was performed in all patients within 24 h of lead implantation or ablation treatment. Statistical correlation analysis of risk factors for intracranial hemorrhage (ICH) was performed by stepwise logistic regression. Explanatory variables were patient age, sex, blood pressure, anatomical targets, the number of microelectrode recording (MER) penetrations and surgical modality.ResultsPostoperative symptomatic ICH occurred in 10 cases (8 pallidotomy and 2 thalamotomy) and asymptomatic ICH in 14 cases (9 pallidotomy, 4 thalamotomy and 1 DBS). Hypertension and surgical modality were significant factors contributing to hemorrhage (both P < 0.05). The likelihood of hemorrhage in hypertensive patients was 2.5 times that in normotensive patients. The risk of hemorrhage during ablation was 5.4 times that in DBS. The number of MER trajectories did not significantly correlate with ICH occurrence (P = 0.07). No statistically significant difference was found in age, sex and anatomical targets.ConclusionThis study demonstrated that hypertension is a risk factor for ICH in PD patients. DBS is generally a safe surgical modality as compared with ablation. Increasing microelectrode trajectories seemed to increase the risk of ICH, but no statistically significant difference was found (P = 0.07).     

Eleven-Year Outcomes of Deep Brain Stimulation in Early-Stage Parkinson Disease

ObjectiveThe deep brain stimulation (DBS) in early-stage Parkinson's disease (PD) pilot clinical trial randomized 30 patients (Hoehn & Yahr II off; medication duration 0.5–4 years; without dyskinesia/motor fluctuations) to optimal drug therapy (ODT) (early ODT) or bilateral subthalamic nucleus (STN) DBS plus ODT (early DBS+ODT). This study aims to report the 11-year outcomes of patients who completed the DBS in early-stage PD pilot clinical trial.Materials and MethodsAttempts were made to contact all 29 subjects who completed the two-year trial to participate in an 11-year follow-up study. Mixed-effects models compared overall trend in outcomes for randomization groups (fixed-effects: assigned treatment, year, their interaction; random-effect: subject) to account for repeated measures.ResultsTwelve subjects participated in this 11-year follow-up study (n = 8 early ODT, n = 4 early DBS+ODT). Participating subjects were 70.0 ± 4.8 years old with a PD medication duration of 13.7 ± 1.7 years (early DBS duration 11.5 ± 1.3 years, n = 4). Three early ODT subjects received STN-DBS as standard of care (DBS duration 6.5 ± 2.0 years). Early ODT subjects had worse motor complications (Unified Parkinson’s Disease Rating Scale [UPDRS]–IV) than early DBS+ODT subjects over the 11-year follow-up period (between-group difference = 3.5 points; p_interaction = 0.03). Early DBS+ODT was well-tolerated after 11 years and showed comparable outcomes to early ODT for other UPDRS domains, Parkinson Disease Questionnaire–39 (PDQ-39), and levodopa equivalent daily dose (LEDD).ConclusionsEleven years after randomization, early DBS+ODT subjects had fewer motor complications than early ODT subjects. These results should be interpreted with caution because only 40% of pilot trial subjects participated in this 11-year follow-up study. The Food and Drug Administration has approved the conduct of a pivotal clinical trial evaluating DBS in early-stage PD (IDEG050016).Clinical Trial RegistrationThe Clinicaltrials.gov registration number for the study is NCT00282152.     

Cognitive and psychiatric outcome 3 years after globus pallidus pars interna or subthalamic nucleus deep brain stimulation for Parkinson's disease

BackgroundEffects on non-motor symptoms, mainly cognitive and psychiatric side effects, could influence the decision for either globus pallidus pars interna (GPi) or subthalamic nucleus (STN) deep brain stimulation (DBS) for patients with Parkinson's disease (PD).Objective1) To compare cognitive and psychiatric outcomes 3 years after GPi DBS versus STN DBS, and 2) to report on occurrence of suicidal ideation, psychiatric diagnoses, social functioning, and marital satisfaction 3 years after DBS.MethodsPatients were randomized to receive GPi DBS (n = 65) or STN DBS (n = 63). Standardized assessments were performed at baseline, 1 year, and 3 years. We used linear mixed model analyses to investigate between-group differences on the Mattis Dementia Rating Scale (MDRS), neuropsychological tests, and psychiatric questionnaires 3 years after DBS.ResultsEighty-seven patients (68%) completed at least one neuropsychological test after 3 years. No significant between-group differences were found on the MDRS (p = 0.61), neuropsychological tests (p-values between 0.17 and 0.87), and psychiatric questionnaires (p-values between 0.23 and 0.88) 3 years after DBS. The Mini International Neuropsychiatric Interview did not indicate a substantial number of psychiatric diagnoses after 3 years. Social functioning and marital satisfaction were comparable in both groups.ConclusionsThree years after GPi DBS and STN DBS no pronounced between-group differences on measures of cognitive and psychiatric functioning could be demonstrated. Overall, cognitive and psychiatric outcome 3 years after DBS do not provide a clear direction for clinicians when considering which of these two surgical targets to choose.     

Combining Multimodal Biomarkers to Guide Deep Brain Stimulation Programming in Parkinson Disease

BackgroundDeep brain stimulation (DBS) programming of multicontact DBS leads relies on a very time-consuming manual screening procedure, and strategies to speed up this process are needed. Beta activity in subthalamic nucleus (STN) local field potentials (LFP) has been suggested as a promising marker to index optimal stimulation contacts in patients with Parkinson disease.ObjectiveIn this study, we investigate the advantage of algorithmic selection and combination of multiple resting and movement state features from STN LFPs and imaging markers to predict three relevant clinical DBS parameters (clinical efficacy, therapeutic window, side-effect threshold).Materials and MethodsSTN LFPs were recorded at rest and during voluntary movements from multicontact DBS leads in 27 hemispheres. Resting- and movement-state features from multiple frequency bands (alpha, low beta, high beta, gamma, fast gamma, high frequency oscillations [HFO]) were used to predict the clinical outcome parameters. Subanalyses included an anatomical stimulation sweet spot as an additional feature.ResultsBoth resting- and movement-state features contributed to the prediction, with resting (fast) gamma activity, resting/movement-modulated beta activity, and movement-modulated HFO being most predictive. With the proposed algorithm, the best stimulation contact for the three clinical outcome parameters can be identified with a probability of almost 90% after considering half of the DBS lead contacts, and it outperforms the use of beta activity as single marker. The combination of electrophysiological and imaging markers can further improve the prediction.ConclusionLFP-guided DBS programming based on algorithmic selection and combination of multiple electrophysiological and imaging markers can be an efficient approach to improve the clinical routine and outcome of DBS patients.     

The actual use of directional steering and shorter pulse width in selected patients undergoing deep brain stimulation

IntroductionDirectional deep brain stimulation (DBS) and pulse with <60μs increase side-effects threshold, enlarging the therapeutic window. However, new systems allowing these advanced features are more expensive and often available only for a limited number of patients in some centers. It is unknown how many and which DBS patients actually need the advanced features because of an insufficient improvement with standard parameters.MethodsWe included in the analysis all patients with Parkinson's disease, dystonia and tremor who were selected to receive implantation of advanced DBS systems based on specific preoperative or intraoperative clinical features.ResultsAfter a median follow-up of 15 months, 54.9% of the 51 patients implanted with directional leads were using the advanced features in one or both leads (n = 42 leads, 42%), meaning these leads were programmed either with directional stimulation (n = 9, 9%), a shorter pw (n = 20, 20%) or both (n = 13, 13%). This included 92% of patients implanted in the Vim, 44% of those implanted in the STN, and 40% of those implanted in the GPi.ConclusionsDBS systems with advanced features may be particularly indicated for selected patients based on some clinical characteristics and the chosen target. This data may help clinicians allocate resources in a more informed way.     

Comparison of intraoperative imaging guided versus microelectrode recording guided deep brain stimulation for Parkinson's disease: A meta-analysis

BackgroundTraditionally, most centers would use microelectrode recording (MER) to refine targeting in deep brain stimulation (DBS) surgery. In recent years, intraoperative imaging (IMG) guided DBS has become an alternative way to verify lead placement. Currently, there is still controversy surrounding the necessity of MER or IMG for DBS. This meta-analysis aims to explore lead accuracy, clinical efficacy and safety between IMG and MER guided DBS for Parkinson's disease (PD).MethodsPubMed, Embase, Web of Science, Cochrane Library were searched up to Mar, 2021 for studies reporting comparisons between IMG and MER guided DBS for PD. Subgroup analysis was conducted to assess effects of different IMG technology and DBS targeting site.ResultsSix studies, comprising of 478 patients were included in our analysis. The mean difference between the two implantation techniques in stereotactic accuracy, lead passes per trajectory, improvement% of Unified Parkinson's Disease Rating Scale part III and levodopa equivalent daily dose were −0.45 (95% confidence interval, CI = −1.11 to 0.20), −0.18 (95% CI = −0.41 to 0.06), 3.40 (95% CI = −5.36 to 12.16), and 5.00 (95% CI = −1.40 to 11.39), respectively. No significant differences were observed in each adverse event and operation/procedure time between the two implantation techniques.ConclusionsBoth IMG and MER guided DBS offered effective control of motor symptoms for PD. Besides, IMG guided is comparable to MER guided DBS, in terms of safety, accuracy and efficiency. It is recommended for each hospital to select DBS guidance technology based on available resources and equipment.     

Increased Subthalamic Nucleus Deep Brain Stimulation Amplitude Impairs Inhibitory Control of Eye Movements in Parkinson's Disease

Background and ObjectivesBilateral subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson's disease (PD) can have detrimental effects on eye movement inhibitory control. To investigate this detrimental effect of bilateral STN DBS, we examined the effects of manipulating STN DBS amplitude on inhibitory control during the antisaccade task. The prosaccade error rate during the antisaccade task, that is, directional errors, was indicative of impaired inhibitory control. We hypothesized that as stimulation amplitude increased, the prosaccade error rate would increase.Materials and MethodsTen participants with bilateral STN DBS completed the antisaccade task on six different stimulation amplitudes (including zero amplitude) after a 12-hour overnight withdrawal from antiparkinsonian medication.ResultsWe found that the prosaccade error rate increased as stimulation amplitude increased (p < 0.01). Additionally, prosaccade error rate increased as the modeled volume of tissue activated (VTA) and STN overlap decreased, but this relationship depended on stimulation amplitude (p = 0.04).ConclusionsOur findings suggest that higher stimulation amplitude settings can be modulatory for inhibitory control. Some individual variability in the effect of stimulation amplitude can be explained by active contact location and VTA-STN overlap. Higher stimulation amplitudes are more deleterious if the active contacts fall outside of the STN resulting in a smaller VTA-STN overlap. This is clinically significant as it can inform clinical optimization of STN DBS parameters. Further studies are needed to determine stimulation amplitude effects on other aspects of cognition and whether inhibitory control deficits on the antisaccade task result in a meaningful impact on the quality of life.     

Deep Brain Stimulation Evoked Potentials May Relate to Clinical Benefit in Childhood Dystonia

BackgroundDeep brain stimulation (DBS) of the globus pallidus internus (GPi) is a treatment for severe childhood-onset dystonia. A common challenge for clinicians is determining which contacts of the DBS electrode to stimulate in order to provide maximum future benefit to the patient.ObjectiveTo characterize how the cortical responses to DBS relate to stimulation parameters (i.e. electrode contacts, voltage, and pulse width) and clinical outcomes.MethodsWe examined 11 patients with dystonia undergoing DBS therapy (9–21 years old when implanted). We varied the active contacts, voltage, and pulse width of the stimulating electrode and analyzed the deep-brain stimulator evoked potentials (DBSEPs) measured with electroencephalogram, and assessed symptoms with the Barry-Albright dystonia scale. Statistical tests included: Repeated measures ANOVA, Mann–Whitney U test and paired t-test.ResultsDBSEPs near sensorimotor areas were larger ipsilaterally than contralaterally (P = 0.007). The rate of DBSEP amplitude increase with respect to stimulator voltage (voltage gain) and pulse width (pulse width gain) varied across subjects and stimulating contacts. Voltage gains were significantly higher among patients who showed larger improvements with DBS (P = 0.038). Additionally, a within-subject comparison of all patients showed that voltage gains were higher for contacts chosen for chronic stimulation as compared to those that were not (P = 0.007).ConclusionsDBSEPs may be good predictors of therapeutic response to stimulation at different electrode contacts. Furthermore, effective DBS therapy appears to modulate sensorimotor cortex. These findings may help clinicians optimize stimulator programming and may eventually lead to improved targeting during implantation.     

Lack of differential motor outcome with subthalamic nucleus region stimulation in Parkinson’s disease

Deep brain stimulation (DBS) has emerged as a viable therapy for Parkinson’s disease (PD). The impact of subthalamic nucleus (STN) lead placement (lateral versus medial) on motor outcome, however, has not been systematically evaluated. Forty-eight patients with PD underwent STN-DBS surgery and were evaluated postoperatively for 48 weeks for motor improvement as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS) part III (standardized motor examination) and levodopa equivalent daily dose (LEDD). Postoperative MRI was used to identify the location of the active stimulating contact and motor outcome was analyzed. STN-DBS was associated with significant improvement in motor outcome as determined by a reduction in the UPDRS part III subscore from 34.44 ± 1.29 at baseline to 18.76 ± 1.06 at end visit (p < 0.0001) and a reduction in LEDD from 1721 ± 152 mg/day at baseline to 1134 ± 119 mg/day at end visit (p = 0.0024). Patients with stimulating contacts in the medial STN compared to the lateral STN did not demonstrate any significant differences in motor outcome (UPDRS, p = 0.5811; LEDD, p = 0.7341). No significant differences were found in motor outcome between patients with STN stimulation compared to stimulation of surrounding fiber tracts (p = 0.80). No significant difference in stimulation voltage was noted with respect to lead location. Our study did not find a significant effect for the location of active contact and motor outcome neither within the subregions of the STN nor between the STN and surrounding fibers. Further research is needed to better understand the neurophysiological basis for these results.     

Phonemic verbal fluency decline after subthalamic nucleus deep brain stimulation does not depend on number of microelectrode recordings or lead tip placement

BackgroundEvidence suggests that both motor improvement and decline in verbal fluency in Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) may be attributed to a lead implantation effect.ObjectiveWe investigated whether the number of microelectrode recording (MER) passes influenced either motor UPDRS scores just prior to stimulation initiation at 4 weeks or decline in verbal fluency 6–24 months after surgery.MethodsWe retrospectively analyzed 50 PD patients who underwent bilateral STN DBS. Off medication UPDRS III motor scores were obtained before surgery and before stimulation was initiated. Neuropsychological testing was completed pre- and post-operatively in 28 patients at a mean of 377 days. Coordinates of lead tip and active stimulation site were calculated.ResultsThere was no improvement in off-medication UPDRS III motor scores at a mean 33.9 days following surgery, with mean change of 0.04 ± 10.48 (p = 0.98). There was no correlation between the number of MER passes and change in individual UPDRS motor score (r = −0.0001, p = 1.0). We observed significant decline in phonemic verbal fluency by 16% (p = 0.003) but it was not correlated with number of left hemisphere (r = −0.15, p = 0.46), or total number of passes (r = −0.02, p = 0.94) or coordinates of the lead tip or active stimulation site. There was a trend toward correlation with age (r = 0.38, p = 0.07).ConclusionsSignificant decline in phonemic verbal fluency did not correlate with surgical passes nor with location of the lead tip or active stimulation site. These data suggest that age may influence verbal fluency decline more than surgical technique.     

Subthalamic Nucleus Deep Brain Stimulation Induces Motor Network BOLD Activation: Use of a High Precision MRI Guided Stereotactic System for Nonhuman Primates

BackgroundFunctional magnetic resonance imaging (fMRI) is a powerful method for identifying in vivo network activation evoked by deep brain stimulation (DBS).ObjectiveIdentify the global neural circuitry effect of subthalamic nucleus (STN) DBS in nonhuman primates (NHP).MethodAn in-house developed MR image-guided stereotactic targeting system delivered a mini-DBS stimulating electrode, and blood oxygenation level-dependent (BOLD) activation during STN DBS in healthy NHP was measured by combining fMRI with a normalized functional activation map and general linear modeling.ResultsSTN DBS significantly increased BOLD activation in the sensorimotor cortex, supplementary motor area, caudate nucleus, pedunculopontine nucleus, cingulate, insular cortex, and cerebellum (FDR < 0.001).ConclusionOur results demonstrate that STN DBS evokes neural network grouping within the motor network and the basal ganglia. Taken together, these data highlight the importance and specificity of neural circuitry activation patterns and functional connectivity.     

Acute Changes in Mood Induced by Subthalamic Deep Brain Stimulation in Parkinson Disease Are Modulated by Psychiatric Diagnosis

BackgroundDeep brain stimulation of the subthalamic nucleus (STN DBS) reduces Parkinson disease (PD) motor symptoms but has unexplained, variable effects on mood.ObjectiveThe study tested the hypothesis that pre-existing mood and/or anxiety disorders or increased symptom severity negatively affects mood response to STN DBS.MethodsThirty-eight PD participants with bilateral STN DBS and on PD medications were interviewed with Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID) and completed Beck Depression Inventory (BDI) and Spielberger State Anxiety Inventory (SSAI) self-reports. Subsequently, during OFF and optimal ON (clinical settings) STN DBS conditions and while off PD medications, motor function was assessed with the United Parkinson Disease Rating Scale (UPDRS, part III), and participants rated their mood with Visual Analogue Scales (VAS), and again completed SSAI. VAS mood variables included anxiety, apathy, valence and emotional arousal.ResultsSTN DBS improved UPDRS scores and mood. Unexpectedly, PD participants diagnosed with current anxiety or mood disorders experienced greater STN DBS-induced improvement in mood than those diagnosed with remitted disorders or who were deemed as having never met threshold criteria for diagnosis. BDI and SSAI scores did not modulate mood response to STN DBS, indicating that clinical categorical diagnosis better differentiates mood response to STN DBS than self-rated symptom severity. SCID diagnosis, BDI and SSAI scores did not modulate motor response to STN DBS.ConclusionsPD participants diagnosed with current mood or anxiety disorders are more sensitive to STN DBS-induced effects on mood, possibly indicating altered basal ganglia circuitry in this group.