Physiological Differences in Pallidal Neurons and Predictors of Therapeutic Success with Deep Brain Stimulation in Jerky Dystonia, Dystonia with Tremor, and Their Combination

Physiological Differences in Pallidal Neurons and Predictors of Therapeutic Success with Deep Brain Stimulation in Jerky Dystonia, Dystonia with Tremor, and Their Combination | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 12 March 2025 V1 Latest version Share on Physiological Differences in Pallidal Neurons and Predictors of Therapeutic Success with Deep Brain Stimulation in Jerky Dystonia, Dystonia with Tremor, and Their Combination Authors : Indiko Dzhalagoniia , Ulia Semenova , Anna Gamaleya , Alexey Tomskiy , Hyder Jinnah , Alexey Sedov 0000-0003-3885-2578 , and Aasef Shaikh 0000-0003-4781-7176 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.174178810.01514399/v1 192 views 163 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Dystonia is characterized by abnormal twisting and turning of body parts, sometimes accompanied by tremulous movements, while tremor involves rhythmic oscillatory movements. These phenomena can coexist, particularly in forms of dystonia that resemble tremor, known as jerky dystonia. This study investigates the physiological differences in pallidal neurons among patients with jerky dystonia, tremor with dystonia, and their combination (mixed dystonia), and identifies neuronal characteristics that predict therapeutic success with deep brain stimulation (DBS). Our analysis of neuronal activity in patients undergoing DBS therapy revealed distinct patterns based on therapeutic effects. In the ’No Effect’ group, neurons had similar characteristics across jerky dystonia, dystonia with tremor, and mixed subgroups, with significant differences in firing rate and preburst interval. The ’Good Effect’ group showed more pronounced differences, with higher firing rates and lower preburst intervals in jerky dystonia compared to dystonia with tremor and mixed dystonia. Dystonia with tremor had higher burst spike percent and longer preburst intervals, while mixed dystonia had the highest preburst interval. These findings indicate that jerky dystonia and tremor with dystonia involve distinct physiological processes, characterized by different neuronal subtypes and firing responses. Mixed dystonia represents a unique physiological process, not merely a combination of the other two. The regions of the pallidum that improve jerky dystonia and tremor are anatomically different. This suggests distinct connectivity patterns and has practical implications for predicting therapeutic success with DBS in different dystonia subtypes. Physiological Differences in Pallidal Neurons and Predictors of Therapeutic Success with Deep Brain Stimulation in Jerky Dystonia, Dystonia with Tremor, and Their Combination Indiko Dzhalagoniya 1 , Ulia Semenova 1 , Anna Gamaleya 2 , Alexey Tomskiy 2 , H. A. Jinnah 3 , Alexey Sedov 1,4 *, Aasef G. Shaikh 5 *. (*Equal contribution) 1 N.N. Semenov Federal Research Center for Chemical Physics Russian Academy of Sciences, Moscow, Russian Federation 2 N.N. Burdenko National Medical Research Center for Neurosurgery, Moscow, Russian Federation 3 Department of Neurology, Emory University, Atlanta, GA 4 Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, Russia 5 Department of Neurology, University Hospitals, Case Western Reserve University, Cleveland, OH Word count: Text: 4728 Abstract: 234 ACKNOWLEDGEMENTS This study was funded by the Russian Science Foundation project 23-15-00487. Shaikh was supported by the Career Development Grant from the American Academy of Neurology, George C. Cotzias Memorial Fellowship, Network Models in Dystonia grant from the Dystonia Medical Research Foundation, and philanthropic funds to the Department of Neurology at University Hospitals (Penni and Stephen Weinberg Chair in Brain Health and Woll Fund). Corresponding Author: Aasef G. Shaikh,MD,PhD Department of Neurology University Hospitals 11100 Euclid Avenue Cleveland OH, 44022 Email: [email protected] Phone: 216-844-1000 Physiological Differences in Pallidal Neurons and Predictors of Therapeutic Success with Deep Brain Stimulation in Jerky Dystonia, Dystonia with Tremor, and Their Combination ABSTRACT Dystonia is characterized by abnormal twisting and turning of body parts, sometimes accompanied by tremulous movements, while tremor involves rhythmic oscillatory movements. These phenomena can coexist, particularly in forms of dystonia that resemble tremor, known as jerky dystonia. This study investigates the physiological differences in pallidal neurons among patients with jerky dystonia, tremor with dystonia, and their combination (mixed dystonia), and identifies neuronal characteristics that predict therapeutic success with deep brain stimulation (DBS). Our analysis of neuronal activity in patients undergoing DBS therapy revealed distinct patterns based on therapeutic effects. In the ’No Effect’ group, neurons had similar characteristics across jerky dystonia, dystonia with tremor, and mixed subgroups, with significant differences in firing rate and preburst interval. The ’Good Effect’ group showed more pronounced differences, with higher firing rates and lower preburst intervals in jerky dystonia compared to dystonia with tremor and mixed dystonia. Dystonia with tremor had higher burst spike percent and longer preburst intervals, while mixed dystonia had the highest preburst interval. These findings indicate that jerky dystonia and tremor with dystonia involve distinct physiological processes, characterized by different neuronal subtypes and firing responses. Mixed dystonia represents a unique physiological process, not merely a combination of the other two. The regions of the pallidum that improve jerky dystonia and tremor are anatomically different. This suggests distinct connectivity patterns and has practical implications for predicting therapeutic success with DBS in different dystonia subtypes. Key Words: dystonia, tremor, globus pallidus, cerebellum, deep brain stimulation, basal ganglia INTRODUCTION Dystonia is characterized most often by abnormal postures, often with slow twisting movements.[1] However, sometimes dystonic movements can be fast and jerky. In many individuals with dystonia, there is co-existing tremor, which is characterized by rhythmic to-and-fro oscillations of a body part. [2], [3] The best ways to describe these various movements has produced some controversy, especially when they overlap.[4] More importantly, whether these different movements reflect varied expressions of the same underlying physiology distinct underlying physiologies is not clear. This investigation addresses a fundamentally important question: whether “jerky dystonia”, “dystonia with tremor”, and their combinations (here called “mixed”) present distinct neurophysiological phenomenologies in single-unit recordings of the basal ganglia in a larger cohort of patients. Additionally, it seeks to determine whether the volume of activated tissue with pallidal deep brain stimulation (DBS) that improves these three types of movements involves specific cell types compared to the volume of activated tissue that improves jerky movements or pure tonic dystonia. Patients Fifteen dystonia patients (jerky dystonia, n=5; dystonia with tremor, n=7; and ‘mixed phenomenologies (both jerking and tremor) participated in the study. All patients underwent DBS implantation surgery into the motor area of the globus pallidus at the N.N. Burdenko Centre for Neurosurgery. The study and research protocol was approved by the institutional review board and ethics committee at N.N. Burdenko Centre for Neurosurgery. The procedures used in this study adhere to the tenets of the Declaration of Helsinki. The participants provided written informed consent prior to enrollment. Pre- and post-operative evaluations Clinical demographics and key features of neurological examination are outlined in Table 1. The features of interest were jerky dystonia, dystonia with tremor, and mixed variant. In addition to neurological examination based classification, the three subtypes were further classified with video based movement analysis. Standardized patient examination videos were recorded according to the Dystonia Study Group Videotape examination protocol[5] and analyzed using computer vision algorithms to assess the waveform characteristics further classifying the phenomenology in jerky dystonia versus dystonia with tremor. Video tracking was done using the CLM-framework package (https://github.com/TadasBaltrusaitis/CLM-framework), identifying facial reference points to reconstruct head movement trajectories. Spectral analysis was used to assess the average spectral power amplitude in the delta (0.5–2 Hz) range for jerky dystonia and the theta (3–6 Hz) range for dystonia with tremor. As amplitudes of different bands can’t be directly compared using OScores[6], the latter values were normalized (Equation 1) to compare jerky dystonia and dystonia with tremor movements. The higher component determined if the patient had jerky dystonia or dystonia with tremor. In the cases when jerky dystonia and dystonia with tremor Oscores differed less than 15%, we considered these patients as “mixed”. The DBS effect was evaluated by calculating the OScore before and after DBS Using the Equation 2. An effect 66% as ‘good effect’, and those in between as ‘moderate effect’. \(\text{Oscore}=\frac{\text{Oscore}{}_{i}\ -\ \text{Oscore}{}_{\min}}{\text{Oscore}{}_{\max}\ -\ \text{Oscore}{}_{\min}}\)(1) \(\text{Effect}=\frac{\text{OScore}{}_{\text{before}\ }-\text{OScore}{}_{\text{after}}}{\text{OScore}{}_{\text{before}}}\times 100\)% (2) Intra-operative measures and computational modeling Participants provided written consent prior to DBS surgery, and the study was approved by the ethics committee at the N.N. Burdenko Neurosurgical Institute. All patients underwent DBS electrode implantation while awake. During surgery, microelectrode registration (MER) and NeuroNavi equipment (AlphaOmega) were used to specify the brain structure for electrode implantation. Microelectrodes (NeuroProbe, AlphaOmega) with impedance between 0.5 to 1 MOhm were used. MER started 15 mm from the target position, advancing in 0.1-0.2 mm steps. Spontaneous single-unit activity (in the absence of voluntary muscle activation) was recorded as the electrode advanced through the GPe and GPi, with recordings containing more than 200 spikes included in the analysis. The signals were preprocessed and analyzed with Offline sorter (Plexon, USA, RRID:SCR_000012). The signal was band-pass filtered (300–5000 Hz) and then aligned for subsequent spike sorting. Amplitude threshold, at the value of 4 times standard deviation, was used to isolate the spikes. Once identified, the single units were separated by manual cluster selection in principal component analysis feature space based on several waveform parameters. Extracted single unit data were then analyzed and all neurons were divided into 3 groups (burst, pause and tonic) depending on neuron activity pattern (Fig. 1A) by using unsupervised clusterization method (Fig. 1B).[7] For each cell we calculated activity parameters such as firing rate, asymmetry index (AI) as ratio of the median to mean interspike intervals (ISI), percent of ISI larger than mean ISI (ISI larger mean), burst spike percent as ratio of spikes in bursts to the total number of spikes and preburst interval. Volume of Activated Tissue The study aimed to determine how pallidal neural activity characteristics in the stimulated area influence the effectiveness of DBS on jerky dystonia versus dystonia with tremor and versus mixed variant. The stimulation zone (Volume of Activated Tissue, VAT) was modeled (LEAD-DBS, RRID:SCR_002915). We subsequently classified neurons recorded during MER as inside or outside the VAT that was therapeutic for jerky dystonia and dystonia with tremor. Neurons’ Localization Upon initiating the MER at a height of 15mm above the target, we successfully recorded both the upper and lower boundaries of the GPe and GPi. This allowed us to accurately calculate the sizes of these structures. Our goal was to analyze the localization of the stimulated neurons. Given that the size of the GP varies among patients, we standardized the recording depth of the neurons using Equation 3. \(\text{Normalized}\ \text{dept}h=\frac{\text{Neuron}^{\prime}s\ \text{dept}h\ -\text{Lower}\ \text{GPi}\ \text{border}\ \times 100}{\text{GPi}\ \text{size}}\)(3) The resulting normalized depth indicates the precise location of neuronal stimulation: at the lower border (normalized depth = 0%), in the middle of GPi (normalized depth = 50%), at the upper border (normalized depth = 100%), or outside GPi (normalized depth > 100%). Statistics Statistical analysis was performed using STATISTICA (RRID:SCR_014213). Post-hoc Dunn’s test detected differences between the three tremor groups and patients with absent and good DBS effects. Mann-Whitney U test was used to compare the ‘Good effect’ and ‘No effect’ groups for each dystonia type. Median values of each parameter were compared, with statistically significant differences considered at p < 0.05. The 25th and 75th quartiles were also analyzed to identify distribution anomalies. Differences in the ratio of burst/pause/tonic neurons in each dystonia group were detected using the χ2 test. RESULTS The overarching goal of this study was to answer following questions: 1) Are there differences in physiology of pallidal neurons in patients with jerky dystonia, tremor with dystonia, and their combination (i.e., mixed)2) Which neuronal characteristics can predict therapeutic success with DBS in those with jerky dystonia, tremor with dystonia, and their combination? In order to answer these questions, we analyzed a total of 944 pallidal neurons inside VAT: 357 neurons from 5 patients with jerky dystonia, 444 neurons from 7 patients with dystonia with tremor and 143 neurons from 3 patients with mixed variant. Influence on therapeutic effect This analysis compared the activity of neurons inside VAT for patients with lack of therapeutic effect from the DBS stimulation and good therapeutic effect (improvement in O-score >66% as a good effect and improvement in O-score <33% as a lack of the effect). The activity of the neurons inside VAT for the patients with jerky dystonia and without effect were characterized by firing rate 64 imp/sec (43 - 93) [median (25th quartile - 75 quartile)] and AI 0.64 (0.61 - 0.71). The ISI larger mean 33% (30 - 35) and burst spike percent 23 (16 - 32) indicate low density of bursts in patients with jerky dystonia. Despite this, the activity pattern does not tend to become more pause with preburst interval 18.4 ms (14 - 30) (Table 2). Pattern clusterization showed that in patients with jerky dystonia 36% of the registered in VAT neurons were burst, 10% were pause and 54% were tonic (Fig.1c,d). The activity of the neurons inside VAT for patients with dystonia with tremor with no effect were characterized by firing rate 61 imp/sec (42 - 84) and AI 0.65 (0.6 – 0.69). The ISI larger mean 34% (31 - 35) and burst spike percent 24% (17 - 34) again as in the jerky dystonia group indicate low density of bursts. Nevertheless, activity pattern tends to become more pause with a high preburst interval 20 ms (16 - 35) (Table 2). Pattern clusterization showed that in patients with dystonia with tremor 53% registered in VAT neurons were burst, 18% were pause and 29% were tonic (Fig.1c,d). The activity of the neurons inside VAT for patients in the Mixed group with no effect were characterized by firing rate 39 imp/sec (23 - 51) and AI 0.7 (0.61 - 0.88). The ISI larger mean 33% (31 - 38) and burst spike percent 18% (7 - 32) indicate even less density of bursts than in patients with dystonia with tremor or jerky dystonia. Nevertheless, activity pattern tends to become even more pause with a high preburst interval 26 ms (23 - 34) (Table 2). Pattern clusterization showed that in patients with Mixed 53% registered in VAT neurons were burst, 16% were pause and 31% were tonic (Fig.1c,d). Statistical analysis showed that neurons from the ‘No effect’ group tend to be similar between jerky dystonia, dystonia with tremor and Mixed subgroups. The significant differences between dystonia groups were found only in two parameters of neuronal activity: firing rate and preburst interval. The firing rate in the Mixed group was significantly lower compared with the jerky dystonia and dystonia with tremor neurons (39 imp/sec vs 64 imp/sec and 61 imp/sec respectively, p-value < 0.05). The preburst interval was significantly higher in the Mixed subgroup compared with the jerky dystonia subgroup (26 ms vs 18.4 ms respectively, p-value < 0.05). It’s quite indicative that no significant differences were found between the jerky dystonia and dystonia with tremor groups. Also, the neuronal composition in three groups was significantly different (the chi-square statistic is 22.3835, the p-value is 0.000168). The activity of the neurons inside VAT for the patients with jerky dystonia and with good effect were characterized by firing rate 65 imp/sec (42 - 89) and AI 0.67 (0.61 - 0.74). The ISI larger mean 33% (31 - 36) and burst spike percent 22% (15 - 31) indicate low density of bursts in patients with jerky dystonia. Despite this, the activity pattern does not tend to be pause with preburst interval 22 ms (13 - 33) (Table 2). Pattern clusterization showed that in patients with jerky dystonia 34% of the registered in VAT neurons were burst, 11% were pause and 55% were tonic (Fig.1c,d). The activity of the neurons inside VAT for patients with dystonia with tremor and with good effect were characterized by firing rate 42 imp/sec (25 - 60) and AI 0.62 (0.52 - 0.69). The ISI larger mean 31% (26 - 33) and burst spike percent 33% (21 - 45) indicate high density of bursts. Nevertheless, activity pattern tends to become more pause with a high preburst interval 34 ms (19 - 54) (Table 2). Pattern clusterization showed that in patients with dystonia with tremor 44% registered in VAT neurons were burst, 24% were pause and 32% were tonic (Fig.1c,d). The activity of the neurons inside VAT for patients with Mixed and with good effect were characterized by firing rate 42 imp/sec (28 - 52) and AI 0.6 (0.51 - 0.68). The ISI larger mean 31% (30 -35) and burst spike percent 31% (20 - 41) indicate high density of bursts. Nevertheless, activity pattern tends to become even more pause than in the jerky dystonia and dystonia with tremor groups with a high preburst interval 37 ms (30 - 47) (Table 2). Pattern clusterization showed that in patients with Mixed 53% registered in VAT neurons were burst, 16% were pause and 31% were tonic (Fig.1c,d). Statistical analysis showed opposite relations between jerky dystonia, dystonia with tremor and Mixed compared with the ‘No effect’ group: all parameters of neuronal activity were statistically significant between the jerky dystonia and dystonia with tremor groups, but not with the Mixed group. The firing rate in the jerky dystonia group was higher than in the dystonia with tremor group (firing rate 65 imp/sec vs 42 imp/sec respectively, p-value < 0.01), and the activity was more regular (AI 0.67 vs 0.62 respectively, p-value < 0.01). The burst density was higher in the dystonia with tremor neurons compared to the jerky dystonia neurons (the ISI larger mean 31% vs 33% respectively, p-value < 0.01 and burst spike percent 33% vs 23% respectively, p-value < 0.01). In the dystonia with tremor group the preburst interval was significantly higher compared with the jerky dystonia group (33.5 ms - 22.4 ms respectively, p-value < 0.01). Which neuronal characteristics determine favorable and not favorable effects of DBS on jerky dystonia, dystonia with tremor and Mixed Neurons in VATs that were associated with significant improvement in the jerky dystonia had a firing rate 65 imp/sec (42 - 89) and AI 0.67 (0.61 - 0.74). These neurons were characterized by low burst density with the ISI larger mean equal to 33% (31 - 36) and burst spike percent equal to 23% (15 - 31). Also, the pattern of neurons with good DBS effect in the jerky dystonia group tend to be pause with a preburst interval 0.0224 ms (0.0128 - 0.0329). (Fig.2a) Neurons in VATs that were associated with no effect in the jerky dystonia had a firing rate 64 imp/sec (43 - 93) and AI 0.64 (0.61 - 0.71). As it was in the group with significant effect, these neurons were characterized by low burst density with the ISI larger mean equal to 33% (30 - 35) and burst spike percent equal to 23% (16 - 32). The pattern of activity was less ‘pause’ activity than in the group with good effect: preburst interval 0.0183 ms (0.0139 - 0.0298).(Fig.2a) Statistical analysis of neuronal activity parameters between ‘Good effect’ and ‘No effect’ groups in the jerky dystonia showed no significant differences in any of the analyzed parameters (Table 2). However, one difference was that in VATs with good effects on jerky dystonia had more pause activity. Neurons in VATs that were associated with significant improvement in the dystonia with tremor had a firing rate 42 imp/sec (25 - 60) and AI 0.62 (0.52 - 0.69). These neurons were characterized by dense bursts according to the ISI larger mean 31% (26 - 33) and the burst spike percent 33% (21 - 45). Also, we noticed that neurons tend to be more paused than in the corresponding jerky dystonia group with preburst interval 0.0335 ms (0.0191 - 0.0541). (Fig.2b) Neurons in VATs that were associated with no effect in the dystonia with tremor had a firing rate 61 imp/sec (42 - 84) and AI 0.65 (0.6 - 0.69). These neurons had less burst density compared with dystonia with tremor neurons with good effect according to the ISI larger mean 34% (31 -35) and the burst spike percent 24% (18 - 34). But the pause activity was lower with preburst interval 0.021 ms (0.016 - 0.035). (Fig.2b) Statistical analysis showed completely opposite results in contrast with the jerky dystonia subgroup. In the dystonia with tremor group the neurons from the ‘Good effect’ group and the ‘No effect’ group significantly differed in each analyzed parameter, except the AI. Neurons from the ‘Good effect’ group in the dystonia with tremor subgroup had lower firing rate than the neurons from the ‘No effect’ group (42 imp/sec vs 61 imp/sec respectively, p-value 0.05). Also, the neurons from the ‘No effect’ group had less burst density than the neurons from the ‘Good effect’ group (ISI larger mean 34% vs 31% respectively, p-value < 0.01 and burst spike percent 24% vs 33% respectively, p-value < 0.01). But with higher burst density the neurons from the ‘Good effect’ group showed more pause activity than the neurons from the ‘No effect’ group (preburst interval 33.5 ms vs 21 ms respectively, p-value < 0.01). (Fig.2b) Neurons in VATs that were associated with significant improvement in the Mixed had a firing rate 42 imp/sec (28 - 52) and AI 0.6 (0.51 - 0.68). These neurons were characterized by moderate density of bursts with ISI larger mean 32% (30 - 35) and burst spike percent 31% (20 - 41). These neurons had the most pause activity between different dystonias with good effect with preburst interval 37 ms (0.03 - 0.047). Neurons in VATs that were associated with no effect in the Mixed had a firing rate 39 imp/sec (23 - 51) and AI 0.7 (0.61 - 0.89). These neurons were characterized by low density of bursts with ISI larger mean 35% (31 - 38) and burst spike percent 18% (7 - 32). The pause activity was moderate according to the preburst interval equal to 25.8 ms (0.0226 - 0.034). Statistical analysis showed that in the Mixed dystonia significant differences between the ‘Good effect’ and ‘No effect’ groups were found only in two parameters of neuronal activity: AI and burst spike percent. Neurons from the ‘Good effect’ group were more irregular than neurons from the ‘No effect’ group (AI 0.6 vs 0.7 respectively, p-value < 0.01) and with almost twofold increase of burst spike percent (18% vs 31% respectively, p-value < 0.05). (Fig.2b) The last comparison was made between all neurons from the group with ‘Good effect’ and from the group with ‘No effect’. In the ‘Good effect’ group the firing rate was 50 imp/sec (30 - 72) and AI 0.64 (0.54 - 0.71). The bursts’ density was on moderate level according to the ISI larger mean equal to 31% (28 - 34) and preburst interval equal to 29% (19 - 41). These neurons were characterized by moderate pause activity with preburst interval equal to 28 ms (17.1 - 47.1). (Fig.2a,b) In the ‘No effect’ group the firing rate was 52 imp/sec (41 - 84) and AI 0.65 (0.61 - 0.72). The bursts were not as dense as they were in the ‘Good effect’ group according to the ISI larger mean equal to 34% (31 - 35) and burst spike percent equal to 24% (16 - 32). The activity of neurons was even less ‘pause’ with preburst interval 22 ms (15.6 - 33.6). (Fig.2a,b) Statistical analysis showed that neurons from the ‘Good effect’ and ‘No effect’ groups significantly differed in all parameters of neuronal activity. In the ‘Good effect’ group the firing rate was lower than in the ‘No effect’ group (50 imp/sec vs 52 imp/sec respectively, p-value < 0.05) and the activity was more irregular (AI 0.64 vs 0.65 respectively, p-value < 0.05). The bursts from the ‘No effect’ group were less dense than from the ‘Good effect’ group according to the ISI larger mean (34% vs 31% respectively, p-value < 0.01) and burst spike percent (22% vs 28% respectively, p-value < 0.01). Also, the neurons from the ‘Good effect’ group tend to be more ‘pausy’ comparing with the neurons from the ‘No effect’ group (preburst interval 26 ms vs 22 ms respectively, p-value <0.01) We also compared interspike interval (ISI) larger mean, and burst spike percent in groups with ‘Good effect’ versus ‘No effect’; and among subgroup of dystonia types (Fig.2c-e). Localization of stimulated neurons We examined the localization of stimulated neurons in relation to individual GPi size, finding no difference in neurons’ localization between the jerky dystonia and the dystonia with tremor groups (p-value = 0.2), but in the Mixed group the localization of stimulated neurons significantly differed from the other two groups (Fig.3a). We also conducted a comparative analysis focusing on neuronal localization between patients who experienced favorable versus unfavorable outcomes from DBS in each dystonia group. Implantation sites for patients with poor outcomes were consistently located significantly lower than those for patients with favorable results (p-value < 0.01 for dystonia with tremor group, p-value 0.05 for Mixed group) (Fig.3b). Comparison with other studies To contextualize our findings, we referenced previous studies. In our study, we observed the mean (median) ± standard deviation (SD) firing rates in the GPe to be 63 (52) ± 40 impulses per second for patients with jerky tremors, and 48 (42) ± 30 impulses per second for those with dystonia with tremor tremors. Similarly, in the GPi, we found firing rates of 61 (51) ± 38 impulses per second for patients with jerky tremors, and 50 (42) ± 31 impulses per second for those with dystonia with tremor. Merello et al. reported a mean ± SD firing rate in the GPe of 54.6 ± 28.6 Hz and in the GPi of 58.01 ± 39.1 Hz among patients with generalized dystonia.[8] Zhuang et al. analyzed discharge rates in the GPi for both primary and secondary dystonias, finding rates of 42.1 ± 23.0 Hz (n=48) and 47.8 ± 19.5 Hz (n=47), respectively.[9] Additionally, Magariños-Ascone et al. documented a mean firing rate of 39 Hz ± 22 in the GPi. This comparison underscores that while our study introduced new insights, it aligns well with the broader body of research on pallidal neuronal activity in dystonia.[10] DISCUSSION Dystonia is characterized by abnormal twisting and turning of body parts, sometimes accompanied by tremulous movements.[2] In contrast, tremor is defined by abnormal rhythmic oscillatory movements.[1] These two distinct phenomena can coexist, and there is ongoing interest in understanding the relationship between them, particularly in forms of dystonia that mimic tremor because they are jerky and repetitive.[11], [12], [13] Jerky dystonia may appear clinically similar to tremor, but objective measures can distinguish the two. Even more intriguing is the combination of jerky dystonia with tremor. The overarching question is how jerky dystonia, tremor, and their combination may differ physiologically. Do these three phenomena merely reflect observable neurological differences from the same pathophysiology, or do they also indicate distinct underlying pathophysiology? Recent literature has shown that the region of the pallidum where DBS leads to improvement in dystonia consists of neurons with different physiological properties compared to regions where DBS is ineffective.[14] Not only is the physiology distinct, but the composition of these neurons into pause, tonic, and burst types also varies in areas where DBS is effective.[14], [15] Our investigation aimed to determine whether the effects of DBS on jerky dystonia, tremor, and their combination are influenced by specific physiological properties of the neurons, and whether such differences are common across these three categories. Our study addressed the following key questions: Are there differences in the physiology of pallidal neurons in patients with jerky dystonia, tremor with dystonia, and their combination (i.e., mixed)? Which neuronal characteristics can predict therapeutic success with DBS in those with jerky dystonia, tremor with dystonia, and their combination? Are there physiological differences in pallidal neurons among patients with jerky dystonia, tremor with dystonia, and mixed (jerky dystonia with tremor)? The analysis of neuronal activity in patients undergoing DBS therapy reveals distinct patterns based on the therapeutic effects observed. In the ’No Effect’ group, neurons exhibited similar characteristics across the jerky dystonia, dystonia with tremor, and mixed subgroups. However, significant differences were identified in two key parameters: firing rate and preburst interval. Specifically, the firing rate was lower in the Mixed group compared to both jerky dystonia and dystonia with tremor groups, while the preburst interval was higher in the Mixed group compared to the jerky dystonia group. Interestingly, no significant differences were found between the jerky dystonia and dystonia with tremor groups. Additionally, the neuronal composition varied significantly among the three groups, highlighting the distinct neuronal activity patterns in patients with different types of dystonia and their response to DBS therapy. In contrast, the ’Good Effect’ group showed more pronounced differences in neuronal activity. For patients with jerky dystonia, the firing rate was higher and the preburst interval was lower compared to those with dystonia with tremor and Mixed dystonia. Patients with dystonia with tremor exhibited a higher burst spike percent and a longer preburst interval compared to those with jerky dystonia. The Mixed group had the highest preburst interval and a firing rate similar to the dystonia with tremor group. Statistical analysis revealed significant differences between the jerky dystonia and dystonia with tremor groups in all parameters of neuronal activity, but not with the Mixed group. This indicates that the neuronal activity patterns in patients with different types of dystonia and their response to DBS therapy are distinct and vary significantly depending on the type of dystonia and the therapeutic effect achieved. Which neuronal characteristics can predict therapeutic success with DBS in those with jerky dystonia, tremor with dystonia, and jerky dystonia with tremor (mixed)? The comparison of neuronal activity in VATs (volume of activated tissue) for patients with different types of dystonia who experienced significant improvement versus those who had no effect from DBS therapy reveals distinct patterns and key differences. For patients with jerky dystonia, the ’Good Effect’ group had a slightly higher preburst interval and more pause activity, but no significant differences were found except for increased pause activity. In dystonia with tremor, the ’Good Effect’ group showed significant differences in all parameters except AI, with lower firing rates, higher burst density, and more pause activity. For mixed dystonia, significant differences were observed in AI and burst spike percent, with the ’Good Effect’ group showing more irregular activity and higher burst spike percent. This highlights distinct neuronal activity patterns in response to DBS therapy across different dystonia types. These results highlight several key observations. Firstly, jerky dystonia and tremor with dystonia involve distinct physiological processes, characterized by different neuronal subtypes within the pallidum and specific firing responses. These differences are particularly pronounced in regions of the pallidum where DBS leads to motor symptom improvement. In contrast, nonresponsive regions do not exhibit significant physiological changes but still show distinct neuronal subtype distributions. Another key observation is that the single-unit pallidal physiology of mixed dystonia, where jerky dystonia coexists with tremor, does not simply combine the characteristics of each condition seen in isolation, as one might predict. Nor is it a ”midway” point or an average of the two, which could suggest different grades of the same physiological process. Instead, it appears to be unique. It is feasible that some aspects of the physiology of jerky dystonia and dystonia with tremor are non-linearly combined, making mixed dystonia appear very distinct. It is possible that the feedback loop leading to jerky dystonia or tremor, when present together, results in unique physiological changes in the target regions. Additionally, the region of the pallidum that improves jerky dystonia is anatomically different from the region that improves tremor. Mixed dystonias fall somewhere in between these regions. This indicates distinct connectivity patterns underlying jerky dystonia and tremor with dystonia. These findings also have practical implications for predicting improvement in jerky dystonia, tremor with dystonia, and their combination, with different predictors for each category. While our study provided novel insights into the physiological differences among various subtypes of dystonia, the overarching features of our neuronal population were consistent with previously published literature. [15], [16]To demonstrate this, we conducted a comprehensive comparison of our findings with existing research on pallidal activity. The primary metric for evaluating neuronal activity was the firing rate, which served as the cornerstone for our comparative analysis. CONCLUSION Our study addressed key questions about the physiological differences in pallidal neurons among patients with jerky dystonia, tremor with dystonia, and their combination (mixed dystonia), and which neuronal characteristics predict therapeutic success with DBS. The analysis revealed distinct neuronal activity patterns based on therapeutic effects. In the ’No Effect’ group, neurons showed similar characteristics across jerky dystonia, dystonia with tremor, and Mixed subgroups, with significant differences in firing rate and preburst interval. The ’Good Effect’ group exhibited more pronounced differences, with jerky dystonia showing higher firing rates and lower preburst intervals compared to dystonia with tremor and Mixed dystonia. Dystonia with tremor had higher burst spike percent and longer preburst intervals, while Mixed dystonia had the highest preburst interval. These findings indicate that jerky dystonia and tremor with dystonia involve distinct physiological processes, with specific neuronal subtypes and firing responses. Mixed dystonia represents a unique physiological process, not just a combination of the other two. The regions of the pallidum that improve jerky dystonia and tremor are anatomically different, with mixed dystonias falling in between. This suggests distinct connectivity patterns and has practical implications for predicting therapeutic success with DBS. Author’s roles Indiko Dzhalagoniia: Data collection and analysis, manuscript preparation and editing Uliya Semenova: Data processing and analysis. Anna Gamaleya: Neurological assessment of dystonia patients, patient recruitment Alexey Tomskiy: Conducting DBS surgeries, data collection. Hyder Jinnah: Manuscript editing, result discussion, study conception Alexey Sedov: Data collection, manuscript editing, study conception, data analysis Aasef Shaikh: Manuscript preparation and editing, study conception, data analysis conception FUNDING This study was funded by the Russian Science Foundation project 23-15-00487. Shaikh was supported by the Career Development Grant from the American Academy of Neurology, George C. Cotzias Memorial Fellowship, Network Models in Dystonia grant from the Dystonia Medical Research Foundation, and philanthropic funds to the Department of Neurology at University Hospitals (Penni and Stephen Weinberg Chair in Brain Health and Woll Fund). The authors have no competing interests to declare that are relevant to the content of this article. ETHICS APPROVAL AND INFORMED CONSENT The study was approved by the institutional review board and the ethics committee of N.N. Burdenko Centre for Neurosurgery. The procedures used in this study adhere to the tenets of the Declaration of Helsinki. Informed consent was obtained from all individual participants included in the study. REFERENCES [1] A. Albanese et al. , “Phenomenology and classification of dystonia: A consensus update,” Mov. Disord. , vol. 28, no. 7, pp. 863–873, Jun. 2013, doi: 10.1002/mds.25475.[2] K. P. Bhatia et al. , “Consensus Statement on the classification of tremors. from the task force on tremor of the International Parkinson and Movement Disorder Society,” Mov. Disord. , vol. 33, no. 1, pp. 75–87, Jan. 2018, doi: 10.1002/mds.27121.[3] G. Deuschl, P. Bain, and M. Brin, “Consensus Statement of the Movement Disorder Society on Tremor,” Mov. Disord. , vol. 13, no. S3, pp. 2–23, Oct. 2008, doi: 10.1002/mds.870131303.[4] A. G. Shaikh and H. A. Jinnah, “Interdisciplinary insights into tremor in dystonia: Navigating clinical controversies, definitional challenges, and pathophysiological complexities,” Parkinsonism Relat. Disord. , vol. 122, p. 106068, May 2024, doi: 10.1016/j.parkreldis.2024.106068.[5] C. L. Comella, S. Leurgans, J. Wuu, G. T. Stebbins, T. Chmura, and and The Dystonia Study Group, “Rating scales for dystonia: A multicenter assessment,” Mov. Disord. , vol. 18, no. 3, pp. 303–312, Mar. 2003, doi: 10.1002/mds.10377.[6] R. C. Mureşan, O. F. Jurjuţ, V. V. Moca, W. Singer, and D. Nikolić, “The Oscillation Score: An Efficient Method for Estimating Oscillation Strength in Neuronal Activity,” J. Neurophysiol. , vol. 99, no. 3, pp. 1333–1353, Mar. 2008, doi: 10.1152/jn.00772.2007.[7] V. Myrov, A. Sedov, A. Tomskiy, L. Myrova, and E. Belova, “A new approach for estimation of spiketrain patterns in basal ganglia.,” Prog. Brain Res. , vol. 249, pp. 321–325, 2019.[8] M. Merello et al. , “Neuronal globus pallidus activity in patients with generalised dystonia,” Mov. Disord. , vol. 19, no. 5, pp. 548–554, May 2004, doi: 10.1002/mds.10700.[9] P. Zhuang, Y. Li, and M. Hallett, “Neuronal activity in the basal ganglia and thalamus in patients with dystonia,” Clin. Neurophysiol. , vol. 115, no. 11, pp. 2542–2557, Nov. 2004, doi: 10.1016/j.clinph.2004.06.006.[10] C. M. Magariños-Ascone, I. Regidor, M. Gómez-Galán, L. Cabañes-Martínez, and R. Figueiras-Méndez, “Deep brain stimulation in the globus pallidus to treat dystonia: Electrophysiological characteristics and 2 years’ follow-up in 10 patients,” Neuroscience , vol. 152, no. 2, pp. 558–571, Mar. 2008, doi: 10.1016/j.neuroscience.2008.01.001.[11] S. B. Beylergil et al. , “Tremor in cervical dystonia,” Dystonia , vol. 3, p. 11309, Mar. 2024, doi: 10.3389/dyst.2024.11309.[12] A. G. Shaikh et al. , “Dystonia and Tremor: A Cross-Sectional Study of the Dystonia Coalition Cohort,” Neurology , vol. 96, no. 4, Jan. 2021, doi: 10.1212/WNL.0000000000011049.[13] A. Shaikh, D. Zee, and H. Jinnah, “Oscillatory Head Movements in Cervical Dystonia: Dystonia, Tremor, or Both?,” Mov. Disord. Off. J. Mov. Disord. Soc. , vol. 30, Apr. 2015, doi: 10.1002/mds.26231.[14] A. Sedov et al. , “Pallidal neuron activity determines responsiveness to deep brain stimulation in cervical dystonia,” Clin. Neurophysiol. , vol. 132, no. 12, pp. 3190–3196, Dec. 2021, doi: 10.1016/j.clinph.2021.07.032.[15] A. Sedov et al. , “Pallidal Activity in Cervical Dystonia with and Without Head Tremor.,” Cerebellum , vol. 19, no. 3, 2020.[16] S. B. Beylergil, A. P. Singh, D. S. Zee, H. A. Jinnah, and A. G. Shaikh, “Relationship between jerky and sinusoidal oscillations in cervical dystonia,” Parkinsonism Relat. Disord. , vol. 66, pp. 130–137, Sep. 2019, doi: 10.1016/j.parkreldis.2019.07.024. Age Sex Tremor type Effect Electrode type Left stimulation contact Right stimulation contact Left stimulation parameters Right stimulation parameters 1 44 M jerky dystonia No Effect Medtronic 3389 1- 2- 9- 10- 0.7 V 210 μs 90 Hz 2.2 V 210 μs 90Hz 2 50 F jerky dystonia No Effect Boston Scientific DB-2201 1- 9- 2.8 mA 120 μs 174 Hz 2.8 mA 120 μs 174 Hz 3 23 F jerky dystonia No Effect Medtronic 3389 0- 8- 2.7 V 120 μs 150 Hz 3.4 V 180 μs 150 Hz 4 54 M jerky dystonia No Effect Boston Scientific DB-2201 1- 2- 9- 10- 2.5 mA 180 μs 130 Hz 2.6mA 90 μs 130 Hz 5 42 M jerky dystonia Good Effect Medtronic 3389 1- 2- 9- 10- 2.8 V 60 μs 200 Hz 2 mA 60 μs 200 Hz 6 39 M jerky dystonia Good Effect Boston Scientific DB-2201 2- 3- 11- 12- 4.1 mA 40 μs 185 Hz 4.1 mA 40 μs 185 Hz 7 32 F jerky dystonia Good Effect Boston Scientific DB-2201 1- 2- 9- 10- 2.5 mA 180 μs 130 Hz 2.6 mA 90 μs 130 Hz 8 52 F jerky dystonia Moderate Effect Medtronic 3389 0- 8- 2.2 V 210 μs 130 Hz 2.2 V 210 μs 130 Hz 9 45 F jerky dystonia Moderate Effect Boston Scientific DB-2201 2- 3- 10- 11- 1.7 mA 60 μs 174 Hz 1.9 mA 60 μs 174 Hz 10 53 F dystonia with tremor No Effect Medtronic 3389 0- 8- 3.2 V 60 μs 170 Hz 3.4 V 60 μs 170 Hz 11 20 F dystonia with tremor No Effect Medtronic 3389 0- 1- 8- 9- 1.2 V 60 μs 180 Hz 1.2 V 60 μs 180 Hz 12 54 F dystonia with tremor Good Effect Medtronic 3389 1- 2- 9- 10- 2.6 V 90 μs 150 Hz 3.2 V 90 μs 150 Hz 13 32 F dystonia with tremor Good Effect Boston Scientific DB-2201 2- 10- 3 mA 90 μs 130 Hz 3 mA 120 μs 130 Hz 14 53 F dystonia with tremor No Effect Medtronic 3389 1- 9- 1.5 V 120 μs 130 Hz 1.5 V 120 μs 130 Hz 15 68 F dystonia with tremor Good Effect Medtronic 3389 0- 1+ 8- 9+ 2.2 V 210 μs 130 Hz 2.2 V 210 μs 130 Hz 16 63 F dystonia with tremor Good Effect Boston Scientific DB-2201 3- 4- 11- 1.1 mA 20 μs 112 Hz 1.5 mA 40 μs 112 Hz 17 36 F dystonia with tremor Good Effect Boston Scientific DB-2201 1- 10- 3 mA 60 μs 174 Hz 2.4 mA 90 μs 174 Hz 18 41 M dystonia with tremor Good Effect Boston Scientific DB-2201 4- 12- 3.6 mA 90 μs 130 Hz 3.5 mA 60 μs 130 Hz Table 1 Short demographic information of recruited patients and the stimulation parameters of utilized DBS electrodes JERKY DYSTONIA VS DYSTONIA WITH TREMOR VS MIXED, NO EFFECT Parameter Median jerky dystonia Median dystonia with tremor Median mixed Lower jerky dystonia Lower dystonia with tremor Lower mixed Upper jerky dystonia Upper dystonia with tremor Upper mixed jerky dystonia-dystonia with tremor, p-value jerky dystonia-mixed, p-value dystonia with tremor-mixed, p-value Firing rate, imp/sec 63.8 60.9 38.7 42.8 41.7 22.8 92.7 84.3 50.8 0.55 0.007 0.046 AI 0.64 0.65 0.7 0.61 0.59 0.61 0.71 0.69 0.88 0.88 0.35 0.17 ISI larger mean, % 33 34 33.5 30 31 31.3 35 35 38 0.97 0.85 0.91 Burst spike percent, % 23 24 18 16 18 7 32 34 32 0.79 0.98 0.76 Preburst interval, ms 18.4 20.7 26 14 16 22.6 30 34.9 34 0.69 0.04 0.13 JERKY DYSTONIA VS DYSTONIA WITH TREMOR VS MIXED, GOOD EFFECT Parameter Median jerky dystonia Median dystonia with tremor Median mixed Lower jerky dystonia Lower dystonia with tremor Lower mixed Upper jerky dystonia Upper dystonia with tremor Upper mixed jerky dystonia-dystonia with tremor jerky dystonia-mixed dystonia with tremor-mixed Firing rate, imp/sec 64.5 41.7 41.5 42.3 24.6 27.8 88.7 60.3 51.6 0.000025 0.005 0.9 AI 0.67 0.62 0.6 0.61 0.52 0.51 0.74 0.69 0.68 0.003 0.09 0.9 ISI larger mean, % 33 31 31 31 26 30 36 33 35 0.00004 0.9 0.3 Burst spike percent, % 23 33 31 15 21 20 31 45 41 0.00004 0.15 0.9 Preburst interval, ms 22.4 33.5 36.5 12.8 19.1 29.2 32.9 54.1 47 0.00008 0.008 0.9 NO EFFECT VS GOOD EFFECT, ALL NEURONS Parameter Median no effect Median good effect Lower no effect Lower good effect Upper no effect Upper good effect p-value Firing rate, imp/sec 52.4 49.6 40.5 29.9 84 71.8 0.03 AI 0.65 0.64 0.61 0.58 0.72 0.71 0.03 ISI larger mean, % 34 31 31 28 35 34 0.0002 Burst spike percent, % 24 29 16 19 32 41 0.003 Preburst interval, ms 22 28 15.6 17.1 33.6 47.1 0.007 NO EFFECT VS GOOD EFFECT, MIXED Parameter Median no effect Median good effect Lower no effect Lower good effect Upper no effect Upper good effect p-value Firing rate, imp/sec 38.7 41.5 22.8 27.8 50.8 51.6 0.8 AI 0.7 0.6 0.61 0.5 0.88 0.7 0.008 ISI larger mean, % 33 31 31 30 38 35 0.08 Burst spike percent, % 18 31 7 20 32 41 0.03 Preburst interval, ms 25.8 36.5 22.6 29.2 34 47 0.09 NO EFFECT VS GOOD EFFECT, DYSTONIA WITH TREMOR Parameter Median no effect Median good effect Lower no effect Lower good effect Upper no effect Upper good effect p-value Firing rate, imp/sec 60.9 41.7 41.7 24.6 84.3 60.3 0.0003 AI 0.65 0.62 0.6 0.52 0.7 0.69 0.052 ISI larger mean, % 34 31 31 26 35 33 0.00002 Burst spike percent, % 24 33 18 21 34 45 0.006 Preburst interval, ms 20.7 33.5 16 19.1 34.9 54.1 0.003 NO EFFECT VS GOOD EFFECT, JERKY DYSTONIA Parameter Median no effect Median good effect Lower no effect Lower good effect Upper no effect Upper good effect p-value Firing rate, imp/sec 63.8 64.5 42.8 42.2 92.7 88.7 0.9 AI 0.64 0.67 0.61 0.61 0.71 0.74 0.5 ISI larger mean, % 33 33 30 31 35 36 0.7 Burst spike percent, % 23 23 16 15 32 31 0.9 Preburst interval, ms 18.3 22.4 13.9 12.8 29.8 32.9 0.6 Table 2 Median and 25/75 quartiles of neuronal activity parameters for patients with jerky dystonia. dystonia with tremor and mixed subgroups in the groups with lack of the effect and good effect. Fig. 1 a - neurogram of each pattern. b - a dendrogram of neurons divided by unsupervised clusterization method. c and d - proportional ratio of neurons with different activity patterns. c - the neuronal composition in the volumes of activated tissue (VAT), which had a good DBS effect and had no effect for different groups of patients (jerky dystonia- jerky dystonia, dystonia with tremor - dystonia with tremor, mixed - mixed variant with dystonia with tremor and jerky dystonia) and all patients. Only in the mixed group the neuronal composition was significantly different (p-value < 0.01). d - the neuronal composition in each dystonia type group compared when effect was good and when effect was not observed. For both groups, with and without effect, the neuronal composition significantly differed between dystonia types (p-value < 0.01) Fig. 2 Boxplots of neuronal activity parameters (a - firing rate, b - asymmetry index (AI), c - percent of interspike intervals(ISI) larger than mean ISI, d - ratio of spikes in bursts to the total number of spikes, e - preburst interval). All neurons were divided in two groups: neurons, which were recorded from patients with no DBS effect (No effect) and from patients with good DBS effect (Good effect). Within each group neurons were divided in jerky dystonia, dystonia with tremor and Mixed subgroups, depending on tremor. Only two parameters significantly differed in a ‘No effect’ group between jerky dystonia and Mixed dystonias: firing rate and preburst interval. No significant differences were found between the dystonia with tremor and Mixed subgroups and the dystonia with tremor and the jerky dystonia subgroups. Opposite to a ‘No effect’ group, ‘Good effect’ group showed significant differences in all observed parameters between the dystonia with tremor and jerky dystonia subgroups and only firing rate was significantly lower in the Mixed dystonia compared to the jerky dystonia. Also, neurons with good effect and no effect significantly differed only in the dystonia with tremor subgroup, not in the jerky dystonia one and partly in the Mixed subgroup. Asterisks show significant differences between groups and subgroups (* - p-value < 0.05) Fig. 3 The localization of stimulated neurons in relation to individual GPi size in a - groups with jerky dystonia, dystonia with tremor and Mixed dystonia and b - groups with good effect and no effect. a. The stimulation depth in the both dystonia with tremor and jerky dystonia groups were significantly higher than the stimulation depth in the Mixed group (p-value < 0.05). b. The stimulation depth in the ‘No effect’ group was significantly lower than in the ‘Good effect’ group for both jerky dystonia and dystonia with tremor dystonias, but not for Mixed dystonia. In the ‘No effect’ group the depth of stimulation was similar for all three dystonia types. In the ‘Good effect’ group the stimulation depth was significantly lower in the Mixed dystonia group compared with the jerky dystonia and dystonia with tremor dystonias. jerky dystonia - jerky dystonia, dystonia with tremor - dystonia with tremor, Mixed - jerky dystonia with tremor. Information & Authors Information Version history V1 Version 1 12 March 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords cerebellum dystonia globus pallidus neurophysiology tremor Authors Affiliations Indiko Dzhalagoniia Semenov Institute of Chemical Physics of the Russian Academy of Sciences View all articles by this author Ulia Semenova N N Burdenko Voronezh State Medical Academy View all articles by this author Anna Gamaleya Burdenko Hospital View all articles by this author Alexey Tomskiy Burdenko Hospital View all articles by this author Hyder Jinnah Emory University View all articles by this author Alexey Sedov 0000-0003-3885-2578 Semenov Institute of Chemical Physics RAS View all articles by this author Aasef Shaikh 0000-0003-4781-7176 [email protected] Case Western Reserve University View all articles by this author Metrics & Citations Metrics Article Usage 192 views 163 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Indiko Dzhalagoniia, Ulia Semenova, Anna Gamaleya, et al. Physiological Differences in Pallidal Neurons and Predictors of Therapeutic Success with Deep Brain Stimulation in Jerky Dystonia, Dystonia with Tremor, and Their Combination. Authorea . 12 March 2025. DOI: https://doi.org/10.22541/au.174178810.01514399/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . Format Please select one from the list RIS (ProCite, Reference Manager) EndNote BibTex Medlars RefWorks Direct import Tips for downloading citations document.getElementById('citMgrHelpLink').addEventListener('click', function() { popupHelp(this.href); return false; }); $(".js__slcInclude").on("change", function(e){ if ($(this).val() == 'refworks') $('#direct').prop("checked", false); $('#direct').prop("disabled", ($(this).val() == 'refworks')); }); View Options View options PDF View PDF Figures Tables Media Share Share Share article link Copy Link Copied! Copying failed. Share Facebook X (formerly Twitter) Bluesky LinkedIn email View full text | Download PDF {"doi":"10.22541/au.174178810.01514399/v1","type":"Article"} Now Reading: Share Figures Tables Close figure viewer Back to article Figure title goes here Change zoom level Go to figure location within the article Download figure Toggle share panel Toggle share panel Share Toggle information panel Toggle information panel Go to previous graphic Go to next graphic Go to previous table Go to next table All figures All tables View all material View all material xrefBack.goTo xrefBack.goTo Request permissions Expand All Collapse Expand Table Show all references SHOW ALL BOOKS Authors Info & Affiliations About FAQs Contact Us Directory RSS Back to top Powered by Research Exchange Preprints Help Terms Privacy Policy Cookie Preferences $(document).ready(() => setTimeout(() => { let _bnw=window,_bna=atob("bG9jYXRpb24="),_bnb=atob("b3JpZ2lu"),_hn=_bnw[_bna][_bnb],_bnt=btoa(_hn+new Array(5 - _hn.length % 4).join(" ")); $.get("/resource/lodash?t="+_bnt); },4000)); (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'9fe6db0b7ceac13d',t:'MTc3OTIzMzA3MQ=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();