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IntroductionDeep brain stimulation (DBS) is widely used for treatment of advanced, medication-refractory Parkinson's disease (PD). However, a significant proportion of patients may suffer adverse effects; up to 10% will present one or more transient or permanent neurobehavioral events.Patient and MethodsIn our case study, a 44-year-old woman diagnosed with PD 6 years previously who was suffering from motor fluctuations, dyskinesia, and freezing of gait episodes was submitted for DBS and implanted with directional electrodes. Intraoperative local field potentials (LFPs) were recorded. After surgery, conventional monopolar revision was performed. Preoperative 3T MRI studies and postoperative 3D and X-ray data were integrated using the Guide DTI software application (Brainlab), and diffusion tensor imaging tractography traced from cortical areas to each subthalamic nucleus (STN) using Elements software (Brainlab).ResultsWe observed that left STN stimulation in the ring mode significantly improved motor symptoms, but the patient presented uncontrollable mirthful laughter. Stimulation was then switched to the directional mode; laughter remained when using the more posteromedial contact (3-C+) but not 2-C+ or 4-C+ at the same parameters. Interestingly, LFP recordings showed the highest beta-band activity over contacts 4 and 2, and very scarce beta power over contact 3. The orientation of the directional leads was selected based on the 3D postoperative X-rays. Associative fibers showed the shortest distance to contact number 3.ConclusionStimulation of the STN can affect motor and associative loops. The use of directional electrodes is a good option to avoid not only undesirable capsular or lemniscal effects, but also limbic/associative events. Oscillatory activity in the beta range that preferentially takes place over the somatomotor STN region and is closely related to motor improvement, provides a reliable guide for optimizing the DBS programming. The importance of the exact location of electrical stimulation to determine the non-motor symptoms such as mood, apathy, attention, and memory, as well as the usefulness of biological markers such as LFP for optimal programming, is discussed in relation to this case.

Introduction: Deep brain stimulation (DBS) is widely used for treatment of advanced, medication-refractory Parkinson's disease (PD). However, a significant proportion of patients may suffer adverse effects; up to 10% will present one or more transient or permanent neurobehavioral events. Patient and Methods: In our case study, a 44-year-old woman diagnosed with PD 6 years previously who was suffering from motor fluctuations, dyskinesia, and freezing of gait episodes was submitted for DBS and implanted with directional electrodes. Intraoperative local field potentials (LFPs) were recorded. After surgery, conventional monopolar revision was performed. Preoperative 3T MRI studies and postoperative 3D and X-ray data were integrated using the Guide DTI software application (Brainlab), and diffusion tensor imaging tractography traced from cortical areas to each subthalamic nucleus (STN) using Elements software (Brainlab). Results: We observed that left STN stimulation in the ring mode significantly improved motor symptoms, but the patient presented uncontrollable mirthful laughter. Stimulation was then switched to the directional mode; laughter remained when using the more posteromedial contact (3-C+) but not 2-C+ or 4-C+ at the same parameters. Interestingly, LFP recordings showed the highest beta-band activity over contacts 4 and 2, and very scarce beta power over contact 3. The orientation of the directional leads was selected based on the 3D postoperative X-rays. Associative fibers showed the shortest distance to contact number 3. Conclusion: Stimulation of the STN can affect motor and associative loops. The use of directional electrodes is a good option to avoid not only undesirable capsular or lemniscal effects, but also limbic/associative events. Oscillatory activity in the beta range that preferentially takes place over the somatomotor STN region and is closely related to motor improvement, provides a reliable guide for optimizing the DBS programming. The importance of the exact location of electrical stimulation to determine the non-motor symptoms such as mood, apathy, attention, and memory, as well as the usefulness of biological markers such as LFP for optimal programming, is discussed in relation to this case. [ABSTRACT FROM AUTHOR]

Sleep disturbances, specifically decreases in total sleep time and sleep efficiency as well as increased sleep onset latency and wakefulness after sleep onset, are highly prevalent in patients with Parkinson's disease (PD). Impairment of sleep significantly and adversely impacts several comorbidities in this patient population, including cognition, mood, and quality of life. Sleep disturbances and other non-motor symptoms of PD have come to the fore as the effectiveness of advanced therapies such as deep brain stimulation (DBS) optimally manage the motor symptoms. Although some studies have suggested that DBS provides benefit for sleep disturbances in PD, the mechanisms by which this might occur, as well as the optimal stimulation parameters for treating sleep dysfunction, remain unknown. In patients treated with DBS, electrophysiologic recording from the stimulating electrode, in the form of local field potentials (LFPs), has led to the identification of several findings associated with both motor and non-motor symptoms including sleep. For example, beta frequency (13–30 Hz) oscillations are associated with worsened bradykinesia while awake and decrease during non-rapid eye movement sleep. LFP investigation of sleep has largely focused on the subthalamic nucleus (STN), though corresponding oscillatory activity has been found in the globus pallidus internus (GPi) and thalamus as well. LFPs are increasingly being recognized as a potential biomarker for sleep states in PD, which may allow for closed-loop optimization of DBS parameters to treat sleep disturbances in this population. In this review, we discuss the relationship between LFP oscillations in STN and the sleep architecture of PD patients, current trends in utilizing DBS to treat sleep disturbance, and future directions for research. In particular, we highlight the capability of novel technologies to capture and record LFP data in vivo, while patients continue therapeutic stimulation for motor symptoms. These technological advances may soon allow for real-time adaptive stimulation to treat sleep disturbances.

Introduction: Up to 27% of individuals undergoing subthalamic nucleus deep brain stimulation (STN-DBS) have a genetic form of Parkinson's disease (PD). Glucocerebrosidase (GBA) mutation carriers, compared to sporadic PD, present with a more aggressive disease, less asymmetry, and fare worse on cognitive outcomes with STN-DBS. Evaluating STN intra-operative local field potentials provide the opportunity to assess and compare symmetry between GBA and non-GBA mutation carriers with PD; thus, providing insight into genotype and STN physiology, and eligibility for and programming of STN-DBS. The purpose of this pilot study was to test differences in left and right STN resting state beta power in non-GBA and GBA mutation carriers with PD.Materials and Methods: STN (left and right) resting state local field potentials were recorded intraoperatively from 4 GBA and 5 non-GBA patients with PD while off medication. Peak beta power expressed as a ratio to total beta power (peak beta ratio) was compared between STN hemispheres and groups while co-varying for age, age of disease onset, and disease severity.Results: Peak beta ratio was significantly different between the left and the right STN for the GBA group (p < 0.01) but not the non-GBA group (p = 0.56) after co-varying for age, age of disease onset, and disease severity.Discussion: Peak beta ratio in GBA mutation carriers was more asymmetric compared with non-mutation carriers and this corresponded with the degree of clinical asymmetry as measured by rating scales. This finding suggests that GBA mutation carriers have a physiologic signature that is distinct from that found in sporadic PD.

Sleep disturbances, specifically decreases in total sleep time and sleep efficiency as well as increased sleep onset latency and wakefulness after sleep onset, are highly prevalent in patients with Parkinson's disease (PD). Impairment of sleep significantly and adversely impacts several comorbidities in this patient population, including cognition, mood, and quality of life. Sleep disturbances and other non-motor symptoms of PD have come to the fore as the effectiveness of advanced therapies such as deep brain stimulation (DBS) optimally manage the motor symptoms. Although some studies have suggested that DBS provides benefit for sleep disturbances in PD, the mechanisms by which this might occur, as well as the optimal stimulation parameters for treating sleep dysfunction, remain unknown. In patients treated with DBS, electrophysiologic recording from the stimulating electrode, in the form of local field potentials (LFPs), has led to the identification of several findings associated with both motor and non-motor symptoms including sleep. For example, beta frequency (13–30 Hz) oscillations are associated with worsened bradykinesia while awake and decrease during non-rapid eye movement sleep. LFP investigation of sleep has largely focused on the subthalamic nucleus (STN), though corresponding oscillatory activity has been found in the globus pallidus internus (GPi) and thalamus as well. LFPs are increasingly being recognized as a potential biomarker for sleep states in PD, which may allow for closed-loop optimization of DBS parameters to treat sleep disturbances in this population. In this review, we discuss the relationship between LFP oscillations in STN and the sleep architecture of PD patients, current trends in utilizing DBS to treat sleep disturbance, and future directions for research. In particular, we highlight the capability of novel technologies to capture and record LFP data in vivo , while patients continue therapeutic stimulation for motor symptoms. These technological advances may soon allow for real-time adaptive stimulation to treat sleep disturbances. [ABSTRACT FROM AUTHOR]

Introduction: Up to 27% of individuals undergoing subthalamic nucleus deep brain stimulation (STN-DBS) have a genetic form of Parkinson's disease (PD). G lucocerebrosidase (GBA) mutation carriers, compared to sporadic PD, present with a more aggressive disease, less asymmetry, and fare worse on cognitive outcomes with STN-DBS. Evaluating STN intra-operative local field potentials provide the opportunity to assess and compare symmetry between GBA and non- GBA mutation carriers with PD; thus, providing insight into genotype and STN physiology, and eligibility for and programming of STN-DBS. The purpose of this pilot study was to test differences in left and right STN resting state beta power in non- GBA and GBA mutation carriers with PD. Materials and Methods: STN (left and right) resting state local field potentials were recorded intraoperatively from 4 GBA and 5 non- GBA patients with PD while off medication. Peak beta power expressed as a ratio to total beta power (peak beta ratio) was compared between STN hemispheres and groups while co-varying for age, age of disease onset, and disease severity. Results: Peak beta ratio was significantly different between the left and the right STN for the GBA group (p < 0.01) but not the non- GBA group (p = 0.56) after co-varying for age, age of disease onset, and disease severity. Discussion: Peak beta ratio in GBA mutation carriers was more asymmetric compared with non-mutation carriers and this corresponded with the degree of clinical asymmetry as measured by rating scales. This finding suggests that GBA mutation carriers have a physiologic signature that is distinct from that found in sporadic PD. [ABSTRACT FROM AUTHOR]

Background: Adaptive Deep Brain Stimulation (aDBS) is now considered as a new feasible and effective paradigm to deliver DBS to patients with Parkinson's disease (PD) in such a way that not only stimulation is personalized and finely tuned to the instantaneous patient's state, but also motor improvement is obtained with a lower amount of energy transferred to the tissue. Amplitude-controlled aDBS was shown to significantly decrease the amplitude-driven total electrical energy delivered to the tissue (aTEED), an objective measure of the amount of energy transferred by DBS amplitude to the patient's brain. However, there is no direct evidence of a relationship between aTEED and the occurrence of DBS-related adverse events in humans.Objective: In this work, we investigated the correlation of aTEED with the occurrence of levodopa-induced dyskinesias pooling all the data available from our previous experiments using aDBS and cDBS.Methods: We retrospectively analyzed data coming from 19 patients with PD undergoing surgery for STN-DBS electrode positioning and participating to experiments involving cDBS and aDBS delivery. Patients were all studied some days after the surgery (acute setting). The aTEED and dyskinesia assessments (Rush Dyskinesia Rating Scale, RDRS) considered in the Med ON-Stim ON condition.Results: We confirmed both that aTEED values and RDRS were significantly lower in the aDBS than in cDBS sessions (aTEED mean value, cDBS: 0.0278 ± 0.0011 j, vs. aDBS: 0.0071 ± 0.0003 j, p < 0.0001 Wilcoxon's rank sum; normalized RDRS mean score, cDBS: 0.66 ± 0.017 vs. aDBS: 0.45 ± 0.01, p = 0.025, Wilcoxon's rank sum test). In addition, we found a direct significant correlation between aTEED and RDRS (ρ = 0.44, p = 0.0032, Spearman's correlation).Conclusions: Our results provide a first piece of evidence that aTEED is correlated to the amount of levodopa-induced dyskinesias in patients with PD undergoing STN-DBS, thus supporting the role of aDBS as feasible and safe alternative to cDBS.

Background: Adaptive Deep Brain Stimulation (aDBS) is now considered as a new feasible and effective paradigm to deliver DBS to patients with Parkinson's disease (PD) in such a way that not only stimulation is personalized and finely tuned to the instantaneous patient's state, but also motor improvement is obtained with a lower amount of energy transferred to the tissue. Amplitude-controlled aDBS was shown to significantly decrease the amplitude-driven total electrical energy delivered to the tissue (aTEED), an objective measure of the amount of energy transferred by DBS amplitude to the patient's brain. However, there is no direct evidence of a relationship between aTEED and the occurrence of DBS-related adverse events in humans. Objective: In this work, we investigated the correlation of aTEED with the occurrence of levodopa-induced dyskinesias pooling all the data available from our previous experiments using aDBS and cDBS. Methods: We retrospectively analyzed data coming from 19 patients with PD undergoing surgery for STN-DBS electrode positioning and participating to experiments involving cDBS and aDBS delivery. Patients were all studied some days after the surgery (acute setting). The aTEED and dyskinesia assessments (Rush Dyskinesia Rating Scale, RDRS) considered in the Med ON-Stim ON condition. Results: We confirmed both that aTEED values and RDRS were significantly lower in the aDBS than in cDBS sessions (aTEED mean value, cDBS: 0.0278 ± 0.0011 j, vs. aDBS: 0.0071 ± 0.0003 j, p < 0.0001 Wilcoxon's rank sum; normalized RDRS mean score, cDBS: 0.66 ± 0.017 vs. aDBS: 0.45 ± 0.01, p = 0.025, Wilcoxon's rank sum test). In addition, we found a direct significant correlation between aTEED and RDRS (ρ = 0.44, p = 0.0032, Spearman's correlation). Conclusions: Our results provide a first piece of evidence that aTEED is correlated to the amount of levodopa-induced dyskinesias in patients with PD undergoing STN-DBS, thus supporting the role of aDBS as feasible and safe alternative to cDBS. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) has been clinically useful in the treatment of PD at all stages, especially in those patients with motor symptoms only partly controlled by dopaminergic drugs, such as severe rest tremor or off-period dystonia, and motor fluctuations. Parkinson's disease, brain stimulation, sleep disturbance, local field potential (LFP), transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS) Keywords: Parkinson's disease; brain stimulation; local field potential (LFP); transcranial direct current stimulation (tDCS); repetitive transcranial magnetic stimulation (rTMS); sleep disturbance; deep brain stimulation (DBS) EN Parkinson's disease brain stimulation local field potential (LFP) transcranial direct current stimulation (tDCS) repetitive transcranial magnetic stimulation (rTMS) sleep disturbance deep brain stimulation (DBS) 1 3 3 06/22/22 20220620 NES 220620 Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, substantially impacting quality of life and economic burden. [Extracted from the article]

Background: Dystonia and Huntington's disease (HD) are both hyperkinetic movement disorders but exhibit distinct clinical characteristics. Aberrant output from the globus pallidus internus (GPi) is involved in the pathophysiology of both HD and dystonia, and deep brain stimulation (DBS) of the GPi shows good clinical efficacy in both disorders. The electrode externalized period provides an opportunity to record local field potentials (LFPs) from the GPi to examine if activity patterns differ between hyperkinetic disorders and are associated with specific clinical characteristics.Methods: LFPs were recorded from 7 chorea-dominant HD and nine cervical dystonia patients. Differences in oscillatory activities were compared by power spectrum and Lempel-Ziv complexity (LZC). The discrepancy band power ratio was used to control for the influence of absolute power differences between groups. We further identified discrepant frequency bands and frequency band ratios for each subject and examined the correlations with clinical scores.Results: Dystonia patients exhibited greater low frequency power (6–14 Hz) while HD patients demonstrated greater high-beta and low-gamma power (26–43 Hz) (p < 0.0298, corrected). United Huntington Disease Rating Scale chorea sub-score was positively correlated with 26–43 Hz frequency band power and negatively correlated with the 6–14 Hz/26–43 Hz band power ratio.Conclusion: Dystonia and HD are characterized by distinct oscillatory activity patterns, which may relate to distinct clinical characteristics. Specifically, chorea may be related to elevated high-beta and low-gamma band power, while dystonia may be related to elevated low frequency band power. These LFPs may be useful biomarkers for adaptive DBS to treat hyperkinetic diseases.

Background: Dystonia and Huntington's disease (HD) are both hyperkinetic movement disorders but exhibit distinct clinical characteristics. Aberrant output from the globus pallidus internus (GPi) is involved in the pathophysiology of both HD and dystonia, and deep brain stimulation (DBS) of the GPi shows good clinical efficacy in both disorders. The electrode externalized period provides an opportunity to record local field potentials (LFPs) from the GPi to examine if activity patterns differ between hyperkinetic disorders and are associated with specific clinical characteristics. Methods: LFPs were recorded from 7 chorea-dominant HD and nine cervical dystonia patients. Differences in oscillatory activities were compared by power spectrum and Lempel-Ziv complexity (LZC). The discrepancy band power ratio was used to control for the influence of absolute power differences between groups. We further identified discrepant frequency bands and frequency band ratios for each subject and examined the correlations with clinical scores. Results: Dystonia patients exhibited greater low frequency power (6–14 Hz) while HD patients demonstrated greater high-beta and low-gamma power (26–43 Hz) (p < 0.0298, corrected). United Huntington Disease Rating Scale chorea sub-score was positively correlated with 26–43 Hz frequency band power and negatively correlated with the 6–14 Hz/26–43 Hz band power ratio. Conclusion: Dystonia and HD are characterized by distinct oscillatory activity patterns, which may relate to distinct clinical characteristics. Specifically, chorea may be related to elevated high-beta and low-gamma band power, while dystonia may be related to elevated low frequency band power. These LFPs may be useful biomarkers for adaptive DBS to treat hyperkinetic diseases. [ABSTRACT FROM AUTHOR]