Clinical asymmetry in Parkinson's disease is characterized by prevalence of subthalamic pause-burst neurons and alpha-beta oscillations.

OBJECTIVE: We aimed to establish specific biomarkers of Parkinson's disease (PD) by comparing activity of more affected (MA) and less affected (LA) subthalamic nucleus (STN) of patients with prominent clinical asymmetry. METHODS: We recorded single unit activity and local field potentials (LFP) of the STN during deep brain stimulation surgeries. Neuronal firing patterns and discharge rate, as well as oscillatory features of both single cells and LFP, were analyzed. RESULTS: We observed notable differences in proportions of irregular-burst and pause-burst, but not tonic neurons, between the hemispheres. Oscillations of pause-burst neurons correlated significantly with the bradykinesia and rigidity scores of the corresponding hemibody. LFP derived from MA STN featured greater power in 12-15 Hz. CONCLUSIONS: Our results provide evidence that the increased proportion of units with prolonged pauses may be associated with PD. We also speculate that some of them may gain rhythmicity in the alpha-beta range in relation to hypokinetic symptoms, long-term disease, or both. SIGNIFICANCE: Our findings highlight the relation between specific oscillatory features of the STN, predominance of subthalamic pause-burst units and PD pathophysiology.

Pallidal multifractal complexity is a new potential physiomarker of dystonia.

OBJECTIVE: Low-frequency 4-12 Hz pallidal oscillations are being considered as potential physiomarkers for dystonia. We suggest investigating the multifractal properties of pallidal activity as an additional marker. METHODS: We employed local field potentials (LFP) recordings from 23 patients with dystonia who were undergoing deep brain stimulation (DBS) surgery to explore the connection between disease severity and the multifractal characteristics of pallidal activity. Furthermore, we performed an analysis of LFP recordings from four patients, following the externalization of DBS lead electrodes, to investigate the impact of DBS and neck muscle vibration on multifractal parameters. RESULTS: Greater dystonia severity exhibited a correlation with a narrower multifractal spectrum width but higher multifractal spectral asymmetry. Both GPi DBS and muscle vibration in dystonia patients expanded the multifractal spectrum width while restoring multifractal spectral symmetry. Notably, the threshold peak intensities for an increase in multifractal spectrum width substantially overlapped with the optimal volume of tissue activated. A broader multifractal spectrum during DBS corresponded to more favorable clinical outcomes. CONCLUSIONS: Multifractal properties of pallidal neuronal activity serve as indicators of neural dysfunction in dystonia. SIGNIFICANCE: These findings suggest the potential of utilizing multifractal characteristics as predictive factors for the DBS outcome in dystonia.

Proprioceptive Modulation of Pallidal Physiology in Cervical Dystonia.

BACKGROUND: There is a growing body of evidence suggesting that botulinum toxin can alter proprioceptive feedback and modulate the muscle-spindle output for the treatment of dystonia. However, the mechanism for this modulation remains unclear. METHODS: We conducted a study involving 17 patients with cervical dystonia (CD), seven of whom had prominent CD and 10 with generalized dystonia (GD) along with CD. We investigated the effects of neck vibration, a form of proprioceptive modulation, on spontaneous single-neuron responses and local field potentials (LFPs) recorded from the globus pallidum externus (GPe) and internus (GPi). RESULTS: Our findings demonstrated that neck vibration notably increased the regularity of neck-sensitive GPi neurons in focal CD patients. Additionally, in patients with GD and CD, the vibration enhanced the firing regularity of non-neck-sensitive neurons. These effects on single-unit activity were also mirrored in ensemble responses measured through LFPs. Notably, the LFP modulation was particularly pronounced in areas populated with burst neurons compared to pause or tonic cells. CONCLUSION: The results from our study emphasize the significance of burst neurons in the pathogenesis of dystonia and in the efficacy of proprioceptive modulation for its treatment. Moreover, we observed that the effects of vibration on focal CD were prominent in the α band LFP, indicating modulation of pallido-cerebellar connectivity. Moreover, the pallidal effects of vibration in GD with CD involved modulation of cerebro-pallidal θ band connectivity. Our analysis provides insight into how vibration-induced changes in pallidal activity are integrated into the downstream motor circuit. © 2023 International Parkinson and Movement Disorder Society.

Does Pallidal Physiology Determine the Success of Unilateral Deep Brain Stimulation in Cervical Dystonia?

Pallidal deep brain stimulation is a well-known surgical treatment for cervical dystonia. The resolution of dystonia typically requires bilateral pallidal stimulation, but in some instances, unilateral stimulation has been successful. In such instances, generally, the stimulated hemisphere was contralateral to the dystonic sternocleidomastoid, but rarely it was ipsilateral. We sought for the physiological features that determine the basis for success and laterality of deep brain stimulation for cervical dystonia with prominent torticollis. We found that pallidal physiology such as high burst to tonic ratio and significant interhemispheric differences in the neuronal firing rate and regularity are critical determinants of successful treatment with unilateral deep brain stimulation. We also found that higher lateralized differences in pallidal physiological parameters predict more robust improvement. In three out of four patients, the stimulation of the hemisphere ipsilateral to the dystonic sternocleidomastoid muscle was effective. These patients did not have any structural brain abnormalities on clinically available imaging studies. One patient responded to the unilateral deep brain stimulation in the hemisphere contralateral to the dystonic sternocleidomastoid. This patient had a structural putamen lesion on brain MRI. These results provide objective parameters determining the success of pallidal deep brain stimulation for treatment of cervical dystonia. The results also depict differences in the pallidal physiology in patients where ipsilateral versus contralateral deep brain stimulation was effective.

DYT1 dystonia: Neurophysiological properties of the pallidal activity.

OBJECTIVES: The aim of this paper is to find the differences in the physiology of the pallidal neurons in DYT1 and non-DYT1 dystonia. METHODS: We performed microelectrode recording of the single unit activity in both segments of the globus pallidus during stereotactic implantation of electrodes for deep brain stimulation (DBS). RESULTS: We found a reduced firing rate, reduced burst rate, and increased pause index in both pallidal segments in DYT1. Also, in DYT1 the activity in both pallidal segments was similar, but not so in non-DYT1. CONCLUSION: The results suggest a common pathological focus for both pallidal segments, located in the striatum. We also speculate that strong striatal influence on GPi and GPe overrides other input sources to the pallidal nuclei causing similarity in neuronal activity. SIGNIFICANCE: We found significant differences in neuronal activity between DYT1 and non-DYT1 neurons. Our findings shed light on the pathophysiology of DYT-1 dystonia which can be very different from non-DYT1 dystonia and have other efficient treatment tactics.

Excessive α-ß Oscillations Mark Enlarged Motor Sign Severity and Parkinson's Disease Duration.

BACKGROUND: ß Oscillations in the subthalamic nucleus (STN) have been proven to contribute to Parkinson's disease (PD), but the exact borders of ß subbands vary substantially across the studies, and information regarding heterogeneity of ß rhythmic activity is still limited. Recently, α oscillations in the basal ganglia have also become the focus of PD research. OBJECTIVES: The aim was to study rhythmic oscillations in the STN in PD patients to identify different subbands with stable oscillatory peaks within a broad α-ß range and to establish their associations with motor symptoms. METHODS: Local field potentials inside the STN were recorded during deep brain stimulation (DBS) surgeries. After calculating power spectra and extracting an aperiodic component, oscillatory peaks in the 8- to 35-Hz range with amplitude exceeding 90th percentile were clustered into three bands. Peak parameters were estimated for two lower subbands. Clinical features were compared in patients with and without oscillation peaks in the lowest α-ß subband. RESULTS: We isolated α-ß (8-15 Hz), ß (15-25 Hz), and ß-γ (25-35 Hz) subbands within the 8- to 35-Hz spectral range using oscillatory parameters and Ward's hierarchical clustering. Additional α-ß oscillatory peaks were found in about half of patients with ß peaks; they were located more ventrally compared to ß. We have found a significant increase in disease duration, bradykinesia, and rigidity scores in the group with additional α-ß peaks. CONCLUSIONS: Increased α-ß oscillations may emerge as additional phenomena complementing ß oscillations; they may mark disease progression in PD and affect DBS stimulation setup. © 2023 International Parkinson and Movement Disorder Society.

Attenuation of neural responses in subthalamic nucleus during internally guided voluntary movements in Parkinson's disease.

The proposed models of segregated functional loops describe the organization of motor control over externally triggered (ET) and internally guided (IG) movements. The dopamine deficiency in Parkinson's disease (PD) is considered to cause a disturbance in the functional loop regulating IG movements. At the same time, the neural mechanisms of movement performance and the role of basal ganglia in motor control remain unclear.The aim of this study was to compare neuronal responses in the subthalamic nucleus (STN) during ET and IG movements in PD. We found and analyzed 26 sensitive neurons in 12 PD patients who underwent surgery for implantation of electrodes for deep brain stimulation. We also analyzed the local field potentials (LFP) of the STN of six patients during the postoperative period. Patients were asked to perform voluntary movements (clenching and unclenching the fist) evoked by verbal command (ET) or self-initiated (IG). We showed heterogeneity of neuronal responses and did not find sensitive neurons associated with only one type of movement. Most cells were characterized by leading responses, indicating that the STN has an important role in movement initiation. At the same time, we found attenuation of motor responses during IG movement vs. stable responses during ET movements. LFP analysis also showed attenuation of beta desynchronization during multiple IG movements.We propose that stable neuronal response to ET movements is associated with the reboot of the motor program for each movement, while attenuation of responses to IG movement is associated with single motor program launching for multiple movements.

Psychogenic (nociplastic) pain: Current state of diagnosis, treatment options, and potentials of neurosurgical management.

Classification of pain syndromes is quite multifaceted. However, pathogenetic classification by which chronic pain syndromes are usually divided into nociceptive, neuropathic and psychogenic, is crucial in choosing treatment tactics. In modern classifications, psychogenic pain is distinguished from nociceptive pain (associated with direct tissue injury or damage) and neuropathic pain (in which lesion can only be determined morphologically). Mental disorders play a leading role in psychogenic pain. Here, somatic/neurological disorders, if any, are of no pathogenetic significance in the dynamics of pain syndrome. There are certain algorithms (though not yet fully developed) and even guidelines for diagnosing and treating nociceptive and neuropathic pain, whereas psychogenic pain has been and still is almost out of sight for a long time. Despite its considerable prevalence, attitude towards it is still uncertain. Until now, it has no single classification, nor any strategy with regards to diagnosis, treatment and prevention.

Patients selection for psychiatric neurosurgery: pitfalls and considerations.

Neurosurgical interventions (destructive or neuromodulation) are considered as a therapeutic option for patients with treatment resistant mental disorders. However, the issues of indications and contraindications for psychiatric surgery, method and patient selection remain unresolved. This article discusses possible problems and contradictions in the selection of patients, the need for an interdisciplinary team to work to solve the question of the feasibility of using neurosurgical methods. The authors have identified the main problems that increase the risks of selection and lead to a lack of results or low efficiency of neurosurgical intervention, namely: (1) diagnostic errors or inaccuracies; (2) inconclusive data on therapeutic resistance; (3) lack of a common understanding of the goals and desired results among participants in the selection of patients for neurosurgery. Possible predictors of surgical outcome and ethical issues are also discussed. Neurosurgical interventions as a treatment option for psychiatric disorders are not officially approved in most countries. So an appropriate algorithm for patient selection and clear criteria for outcome measures are needed.

Gamma Knife capsulotomy for correction of obsessive-compulsive symptoms in a patient with schizophrenia: Case report.

The treatment of mental illnesses that are resistant to conservative therapy poses a serious problem. Surgical methods with proven efficacy have been proposed for only a small group of psychiatric diseases, while in practice non-classical clinical situations are seen rather often. A 36-year-old man with a 18-year history of "schizophrenia with a predominant obsessive-compulsive syndrome" was referred to the Burdenko National Medical Research Center of Neurosurgery for consideration of neurosurgical treatment. Based on results of longitudinal independent evaluations of the patient in several specialized clinical centers the disease was considered resistant to medical therapy. Radiosurgical procedure was performed by means of Leksell Gamma Knife Perfexion™ (Elekta AB; Stockholm, Sweden). Ventral portion of the anterior limb of internal capsule was targeted with two 4-mm isocenters on each side, with prescription dose at 50% isodose line of 80 Gy and a maximal dose of 160 Gy. No obvious complications or side effects were noted during 13-month follow-up after radiosurgery. Gradual clinical improvement was observed with 25% reduction of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score at 13 months after treatment. Similarly, the Hospital Anxiety and Depression Scale (HADS) anxiety and depression scores decreased by 24% and 58%, respectively. This is the first published case of radiosurgical treatment of a psychiatric disorder in Russia. It demonstrates the potential efficacy of Gamma Knife capsulotomy for non-classical forms of obsessive-compulsive disorder comorbid with schizophrenia. Nevertheless, definitive conclusions about the reliability of this radiosurgical indication can only be made based on the results of larger studies.

Neurosurgical management of Tourette syndrome: A literature review and analysis of a case series treated with deep brain stimulation.

Tourette syndrome (TS) is a heterogeneous disorder, which clinical presentation includes both multiple motor and vocal tics and commonly associated psychiatric conditions (obsessive-compulsive disorder, attention deficit hyperactivity disorder, depression, anxiety, etc.). Treatment options primarily consist of non-pharmacological interventions (habit reversal training, relaxation techniques, cognitive behavioral therapy, and social rehabilitation) and pharmacotherapy. In case of the intractable forms, neurosurgical treatment may be considered, primarily deep brain stimulation (DBS). DBS appear to be effective in medically intractable TS patients, although, the preferential brain target is still not defined. The majority of studies describe small number of cases and the issues of appropriate patient selection and ethics remain to be clarified. In this article, we review the main points in management of TS, discuss possible indications and contraindications for neurosurgical treatment, and analyze our experience of DBS in a case series of refractory TS patients with the focus on target selection and individual outcomes.

Oscillations of pause-burst neurons in the STN correlate with the severity of motor signs in Parkinson's disease.

BACKGROUND: Oscillatory activity in the subthalamic nucleus (STN) in Parkinson's disease (PD) is under extensive study. While rhythmic features of local field potentials are implicated in the manifestation of PD motor signs, less is known about single unit activity (SUA). SUA parameters inside the STN show significant heterogeneity, and various firing patterns may contribute unequally to PD pathophysiology. OBJECTIVES: We searched for correlations between SUA parameters and PD motor signs, taking neuronal activity patterns into account. METHODS: 829 spike trains for STN SUA were recorded during 25 DBS surgeries. We have isolated three firing patterns (tonic, irregular-burst and pause-burst) and, using mixed linear models, examined several spiking parameters and burst descriptors (for the last two patterns) for their correlation with UPDRS-III PD motor signs in the contralateral hemibody. RESULTS: The predominance of pause-burst as opposed to tonic activity was associated with a higher PD motor sign severity UPDRS-III. Spike synchronization in the alpha and beta range correlated positively with bradykinesia scores only for pause-burst neurons, while spike synchrony in the theta frequency (4-8 Hz) in these neurons showed an inverse correlation with bradykinesia scores. Other patterns showed no correlation with PD motor signs. CONCLUSIONS: Our work demonstrates the PD motor state is associated with distinct changes in firing patterns and oscillatory synchronization that can be associated with PD motor sign severity. Here, pause-burst patterns were identified as most informative, potentially reflecting a progressive shift from tonic to burst to rhythmic activity in the alpha and beta frequency bands in the parkinsonian state.

Pallidal neuron activity determines responsiveness to deep brain stimulation in cervical dystonia.

OBJECTIVE: In patients with cervical dystonia we sought for the differences in neuronal behavior of pallidal regions where deep brain stimulation resulted in favorable therapeutic response compared to those where the response was absent. METHODS: We compared single-unit activity of 564 neurons recorded from deep brain stimulation sensitive and non-sensitive regions in 17 cervical dystonia patients. RESULTS: Globus pallidus internus regions responsive to the deep brain stimulation had lower firing rates and bursting compared to non-responsive areas. The differences were robust in locations where neuronal responses correlated with neck movements. Per the effects of deep brain stimulation, the pallidal regions were classified in weak, intermediate, and excellent responsive. Pallidal regions with weak response to deep brain stimulation had fewer burst neurons and higher firing rate compared to neurons in areas with excellent response. The burst index was significantly decreased in excellent response regions. There was a significant decrease in the alpha band oscillation score but a substantial increase in the gamma band in excellent response neurons. CONCLUSION: The pallidal region that would be responsive to deep brain stimulation has distinct physiology compared to the non-responsive region. SIGNIFICANCE: These results provide novel insights into globus pallidus interna neurons' physiology in cervical dystonia.

Is there a single beta oscillation band interfering with movement in Parkinson's disease?

Beta oscillations in basal ganglia are considered to contribute to motor dysfunction in Parkinson's disease (PD). However, there is a high variety in frequency borders for beta oscillations between studies, which complicates the comparison and interpretation of results. Here we aimed to study the homogeneity of oscillations in the broad "beta" range (8-30 Hz) and their implication to motor functioning in PD. For this purpose, we recorded local field potentials (LFP) in the subthalamic nucleus (STN) during 34 deep brain stimulation surgeries. We identified spectral features of LFP recordings in the range 8-30 Hz to search for candidate sub-regions of stable oscillations and assessed their association with clinical scores on the contralateral side of the body and sensitivity to motor tests. Lower frequency oscillations (8-16 Hz) had a significant positive association with bradykinesia score. During voluntary movements, we observed a significant increase in LFP power in the 12-16 Hz range and a decrease in the 18-26 Hz range. We may conclude that the 8-30 Hz oscillation range includes oscillations with different functional features-sensitivity and responsiveness to movement, and clinical symptoms, which should be taken into account in further studies of beta oscillations association with PD pathophysiology. These data assume the coexistence of several frequency domains within beta range that are modulated in different ways under dopaminergic regulation and motor processing in human STN.

Voluntary movements cause beta oscillations increase and broadband slope decrease in the subthalamic nucleus of parkinsonian patients.

Periodic features of local field potentials (LFP) are extensively studied to establish the pathophysiological features contributing to Parkinson's disease (PD). Pathological LFP synchronization in the subthalamic nucleus (STN) was assumed to link with motor signs of PD. Commonly, the association between oscillations and clinical signs is studied while the patients are at rest. However, changes in LFPs during movement may reflect particular traits of motor processing in the basal ganglia under PD. Recently, the aperiodic 1/f broadband component of LFP spectra has attracted the attention of researchers because it may provide meaningful information about the neural activity in the brain. Here, we compared LFP signals in the STN of parkinsonian patients at rest and during hand movements occasionally followed by leg movements using two approaches, one of which accounts for the aperiodic features of LFP spectra. Using both methods, a significant increase was observed in synchronization in the low beta range during sequent leg but not hand movements. For either movement, there was a significant increase in gamma range synchronization using uncorrected power spectra and a significant decrease in the slope of the aperiodic component for the 1/f-corrected method. These findings may support the claim that the 1/f slope possibly reflects the excitatory/inhibitory projections ratio in the recording site. Only the difference in the slope correlated significantly with motor signs of PD. These data show that the slope of aperiodic component may be a useful measure that is sensitive to the specific state and its changes in the brain.

Pallidal 1/f asymmetry in patients with cervical dystonia.

Lateralized differences in pallidal outflow are putatively linked to asymmetric tonic contractions of the neck muscles in cervical dystonia (CD). At the population level, the interhemispheric asymmetry has been traditionally studied for the estimation of the spectral power in specified frequency bands. Broadband spectral features, however, were not taken into consideration. The contemporary analysis revealed that the aperiodic (1/f) broadband activity could be a neurophysiological marker of the excitation/inhibition ratio. During deep brain stimulation (DBS) surgery, we measured bilateral pallidal local field potentials (LFP) in nine CD patients, examining the effects of lateralized asymmetry on 1/f broadband activity. All patients showed a trend towards an asymmetric difference in the 1/f broadband activity. The ipsilateral 1/f slope was significantly higher in internal (GPi) segment of the globus pallidus that is on the contralateral side of the direction of the dystonia. We also found lateralized differences in the beta oscillations for GPi and in the alpha oscillations for GPe. Our findings emphasize the importance of mainstreaming broadband activity in the estimation of LFP spectral features together with periodic features and provide further evidence for the pallidal asymmetry in CD patients.

Feedback-dependent neuronal properties make focal dystonias so focal.

Focal dystonia, by definition, affects a specific body part; however, it may have a widespread neural substrate. We tested this hypothesis by examining the intrinsic behaviour and the neuronal properties that are modulated by changes in the physiological behaviour of their connections, that is feedback dependence, of the isolated pallidal neurons. During deep brain stimulation surgery in 12 patients with isolated cervical dystonia (without hand involvement), we measured spontaneous as well as evoked single-unit properties in response to fist making (hand movement) or shoulder shrug (neck movements). We measured the activity of isolated neurons that were only sensitive to the neck movements, hand movement, or not responsive to hand or neck movements. The spontaneous firing behaviour, such as the instantaneous firing rate and its regularity, was comparable in all three types of neurons. The neck movement-sensitive neurons had prominent bursting behaviour in comparison with the hand neurons. The feedback dependence of the neck movement-sensitive neurons was also significantly impaired when compared to hand movement-sensitive neurons. Motor-evoked change in firing rate of neck movement-sensitive neurons rapidly declined; the decay time constant was much shorter compared to hand movement-sensitive neurons. These results suggest that in isolated cervical dystonia, at the resolution of single neurons, the deficits are much widespread, affecting the neurons that drive the neck movement as well as the hand movements. We speculate that clinically discernable dystonia occurs when additional abnormality is added to baseline dysfunctional network, and one source of such abnormality may involve feedback.

Pallidal Activity in Cervical Dystonia with and Without Head Tremor.

The relationship between two common movement disorders, dystonia and tremor, is controversial. Both deficits have correlates in the network that includes connections between the cerebellum and the basal ganglia. In order to assess the physiological relationship between tremor and dystonia, we measured the activity of 727 pallidal single-neurons during deep brain stimulation surgery in patients with cervical dystonia without head oscillations, cervical dystonia plus jerky oscillations, and cervical dystonia with sinusoidal oscillations. Cluster analyses of spike-train recordings allowed classification of the pallidal activity into burst, pause, and tonic. Burst neurons were more common, and number of spikes within spike and inter-burst intervals was shorter in pure dystonia and jerky oscillation groups compared to the sinusoidal oscillation group. Pause neurons were more common and irregular in pure tremor group compared to pure dystonia and jerky oscillation groups. There was bihemispheric asymmetry in spontaneous firing discharge in pure dystonia and jerky oscillation groups, but not in sinusoidal oscillation group. These results demonstrate that the physiology of pallidal neurons in patients with pure cervical dystonia is similar to those who have cervical dystonia combined with jerky oscillations, but different from those who have cervical dystonia combined with sinusoidal oscillations. These results imply distinct mechanistic underpinnings for different types of head oscillations in cervical dystonia.

Hyperactivity of Basal Ganglia in Patients With Parkinson's Disease During Internally Guided Voluntary Movements.

The contribution of different brain areas to internally guided (IG) and externally triggered (ET) movements has been a topic of debate. It has been hypothesized that IG movements are performed mainly through the basal ganglia-thalamocortical loop while ET movements are through the cerebello-thalamocortical pathway. We hypothesized that basal ganglia activity would be modified in patients with Parkinson's disease during IG movement as compared with normal subjects. We used functional MRI (fMRI) to investigate the differences between IG and ET motor tasks. Twenty healthy participants and 20 Parkinson's disease patients (OFF-state) were asked to perform hand movements in response to sound stimuli (ET) and in advance of the stimuli (IG). We showed that ET movements evoked activation of a few large clusters in the contralateral motor areas: the sensorimotor and premotor cortex, supplementary motor area (SMA), insula, putamen, motor thalamus and ipsilateral cerebellum. IG movements additionally evoked activation of a large number of small clusters distributed in different brain areas including the parietal and frontal lobes. Comparison between the activity of Parkinson's disease patients and healthy volunteers showed few important differences. We observed that along with the activity of the posterior areas, an activation of the anterior areas of putamen was observed during IG movements. We also found hyperactivity of the ventral thalamus for both movements. These results showed that IG movements in PD patients were made with the involvement of both sensorimotor and associative basal ganglia-thalamocortical loops.

Implications of asymmetric neural activity patterns in the basal ganglia outflow in the integrative neural network model for cervical dystonia.

Cervical dystonia (CD) is characterized by abnormal twisting and turning of the head with associated head oscillations. It is the most common form of dystonia, which is a third most common movement disorder. Despite frequent occurrence there is paucity in adequate therapy, much of which is attributed to its uncertain pathophysiology. Recently we proposed a unifying network model highlighting the role of head neural integrator (hNI) for the pathophysiology of CD. According to our hypothesis the CD is due to abnormal output of hNI; the latter itself is not affected but its dysfunction is secondary to abnormal feedback. We hypothesized that asymmetry in the feedback to hNI is associated with severity in CD; the feedback asymmetry is greater in CD with lateralized head postures, such as turning of head in yaw plane (torticollis) or roll plane (laterocollis). The hypothesis also specifies that feedback to hNI-cerebellum, proprioception, and basal ganglia outflow (pallidus) are connected in a network; thus asymmetry is distributed through the feedback network. In 15 CD patients undergoing deep brain stimulation (DBS) surgery, with their informed consent, we used the opportunity to collect single unit neural responses and local field potential from the globus pallidus to measure whether feedback to hNI is asymmetric. Using machine learning algorithms developed to analyze single unit data, we found: (1) globus pallidus interna (GPi) firing rate, discharge pattern and gamma oscillation were asymmetric in patients with robust torticollis; (2) there was no asymmetry in these parameters in retrocollis; and (3) in those patients with oppositely directed laterocollis and torticollis. Firing rate was higher in GPi cells ipsilateral to the direction of head rotation; the asymmetry was more pronounced in tonic cells compared to burst neurons. In addition to confirming that CD is associated with an asymmetric pallidal activity, our data showed that neuronal asymmetry correlated with the degree of involuntary head turning. We propose that asymmetric pallidal activity results in asymmetric feedback to hNI causing its dysfunction.