Parkinsonian Tremor Research Articles

Magnetic resonance–guided focused ultrasound thalamotomy for tremor: a report of 30 Parkinson's disease and essential tremor cases

OBJECTIVE Thalamotomy of the ventral intermediate nucleus (VIM) is effective in alleviating medication-resistant tremor in patients with essential tremor (ET) and Parkinson's disease (PD). MR-guided focused ultrasound (MRgFUS) is an innovative technology that enables noninvasive thalamotomy via thermal ablation. METHODS Patients with severe medication-resistant tremor underwent unilateral VIM thalamotomy using MRgFUS. Effects on tremor were evaluated using the Clinical Rating Scale for Tremor (CRST) in patients with ET and by the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with PD and ET-PD (defined as patients with ET who developed PD many years later). Quality of life in ET was measured by the Quality of Life in Essential Tremor (QUEST) questionnaire and in PD by the PD Questionnaire (PDQ-39). RESULTS Thirty patients underwent MRgFUS, including 18 with ET, 9 with PD, and 3 with ET-PD. The mean age of the study population was 68.9 ± 8.3 years (range 46-87 years) with a mean disease duration of 12.1 ± 8.9 years (range 2-30 years). MRgFUS created a lesion at the planned target in all patients, resulting in cessation of tremor in the treated hand immediately following treatment. At 1 month posttreatment, the mean CRST score of the patients with ET decreased from 40.7 ± 11.6 to 9.3 ± 7.1 (p < 0.001) and was 8.2 ± 5.0 six months after treatment (p < 0.001, compared with baseline). Average QUEST scores decreased from 44.8 ± 12.9 to 13.1 ± 13.2 (p < 0.001) and was 12.3 ± 7.2 six months after treatment (p < 0.001). In patients with PD, the mean score of the motor part of the UPDRS decreased from 24.9 ± 8.0 to 16.4 ± 11.1 (p = 0.042) at 1 month and was 13.4 ± 9.2 six months after treatment (p = 0.009, compared with baseline). The mean PDQ-39 score decreased from 38.6 ± 16.8 to 26.1 ± 7.2 (p = 0.036) and was 20.6 ± 8.8 six months after treatment (p = 0.008). During follow-up of 6-24 months (mean 11.5 ± 7.2 months, median 12.0 months), tremor reappeared in 6 of the patients (2 with ET, 2 with PD, and 2 with ET-PD), to a lesser degree than before the procedure in 5. Adverse events that transiently occurred during sonication included headache (n = 11), short-lasting vertigo (n = 14) and dizziness (n = 4), nausea (n = 3), burning scalp sensation (n = 3), vomiting (n = 2) and lip paresthesia (n = 2). Adverse events that lasted after the procedure included gait ataxia (n = 5), unsteady feeling (n = 4), taste disturbances (n = 4), asthenia (n = 4), and hand ataxia (n = 3). No adverse event lasted beyond 3 months. Patients underwent on average 21.0 ± 6.9 sonications (range 14-45 sonications) with an average maximal sonication time of 16.0 ± 3.0 seconds (range 13-24 seconds). The mean maximal energy reached was 12,500 ± 4274 J (range 5850-23,040 J) with a mean maximal temperature of 56.5° ± 2.2°C (range 55°-60°C). CONCLUSIONS MRgFUS VIM thalamotomy to relieve medication-resistant tremor was safe and effective in patients with ET, PD, and ET-PD. Current results emphasize the superior adverse events profile of MRgFUS over other surgical approaches for treating tremor with similar efficacy. Large randomized studies are needed to assess prolonged efficacy and safety.

A proof-of-principle simulation for closed-loop control based on preexisting experimental thalamic DBS-enhanced instrumental learning

Deep brain stimulation (DBS) has been applied as an effective therapy for treating Parkinson's disease or essential tremor. Several open-loop DBS control strategies have been developed for clinical experiments, but they are limited by short battery life and inefficient therapy. Therefore, many closed-loop DBS control systems have been designed to tackle these problems by automatically adjusting the stimulation parameters via feedback from neural signals, which has been reported to reduce the power consumption. However, when the association between the biomarkers of the model and stimulation is unclear, it is difficult to develop an optimal control scheme for other DBS applications, i.e., DBS-enhanced instrumental learning. Furthermore, few studies have investigated the effect of closed-loop DBS control for cognition function, such as instrumental skill learning, and have been implemented in simulation environments. In this paper, we proposed a proof-of-principle design for a closed-loop DBS system, cognitive-enhancing DBS (ceDBS), which enhanced skill learning based on in vivo experimental data. The ceDBS acquired local field potential (LFP) signal from the thalamic central lateral (CL) nuclei of animals through a neural signal processing system. A strong coupling of the theta oscillation (4–7 Hz) and the learning period was found in the water reward-related lever-pressing learning task. Therefore, the theta-band power ratio, which was the averaged theta band to averaged total band (1–55 Hz) power ratio, could be used as a physiological marker for enhancement of instrumental skill learning. The on-line extraction of the theta-band power ratio was implemented on a field-programmable gate array (FPGA). An autoregressive with exogenous inputs (ARX)-based predictor was designed to construct a CL-thalamic DBS model and forecast the future physiological marker according to the past physiological marker and applied DBS. The prediction could further assist the design of a closed-loop DBS controller. A DBS controller based on a fuzzy expert system was devised to automatically control DBS according to the predicted physiological marker via a set of rules. The simulated experimental results demonstrate that the ceDBS based on the closed-loop control architecture not only reduced power consumption using the predictive physiological marker, but also achieved a desired level of physiological marker through the DBS controller.

Tremor analysis separates Parkinson's disease and dopamine receptor blockers induced parkinsonism.

Parkinson's disease, the most common cause of parkinsonism is often difficult to distinguish from its second most common etiology due to exposure to dopamine receptor blocking agents such as antiemetics and neuroleptics. Dual axis accelerometry was used to quantify tremor in 158 patients with parkinsonism; 62 had Parkinson's disease and 96 were clinically diagnosed with dopamine receptor blocking agent-induced parkinsonism. Tremor was measured while subjects rested arms (resting tremor), outstretched arms in front (postural tremor), and reached a target (kinetic tremor). Cycle-by-cycle analysis was performed to measure cycle duration, oscillation amplitude, and inter-cycle variations in the frequency. Patients with dopamine receptor blocker induced parkinsonism had lower resting and postural tremor amplitude. There was a substantial increase of kinetic tremor amplitude in both disorders. Postural and resting tremor in subjects with dopamine receptor blocking agent-induced parkinsonism was prominent in the abduction-adduction plane. In contrast, the Parkinson's disease tremor had equal amplitude in all three planes of motion. Tremor frequency was comparable in both groups. Remarkable variability in the width of the oscillatory cycles suggested irregularity in the oscillatory waveforms in both subtypes of parkinsonism. Quantitative tremor analysis can distinguish Parkinson's disease from dopamine receptor blocking agent-induced parkinsonism.

Design of robust adaptive controller and feedback error learning for rehabilitation in Parkinson's disease: a simulation study.

Deep brain stimulation (DBS) is an efficient therapy to control movement disorders of Parkinson's tremor. Stimulation of one area of basal ganglia (BG) by DBS with no feedback is the prevalent opinion. Reduction of additional stimulatory signal delivered to the brain is the advantage of using feedback. This results in reduction of side effects caused by the excessive stimulation intensity. In fact, the stimulatory intensity of controllers is decreased proportional to reduction of hand tremor. The objective of this study is to design a new controller structure to decrease three indicators: (i) the hand tremor; (ii) the level of delivered stimulation in disease condition; and (iii) the ratio of the level of delivered stimulation in health condition to disease condition. For this purpose, the authors offer a new closed-loop control structure to stimulate two areas of BG simultaneously. One area (STN: subthalamic nucleus) is stimulated by an adaptive controller with feedback error learning. The other area (GPi: globus pallidus internal) is stimulated by a partial state feedback (PSF) controller. Considering the three indicators, the results show that, stimulating two areas simultaneously leads to better performance compared with stimulating one area only. It is shown that both PSF and adaptive controllers are robust regarding system parameter uncertainties. In addition, a method is proposed to update the parameters of the BG model in real time. As a result, the parameters of the controllers can be updated based on the new parameters of the BG model.

Cognitive Stress Reduces the Effect of Levodopa on Parkinson's Resting Tremor.

SummaryAimsResting tremor in Parkinson′s disease (PD) increases markedly during cognitive stress. Dopamine depletion in the basal ganglia is involved in the pathophysiology of resting tremor, but it is unclear whether this contribution is altered under cognitive stress. We test the hypothesis that cognitive stress modulates the levodopa effect on resting tremor.MethodsTremulous PD patients (n = 69) were measured in two treatment conditions (OFF vs. ON levodopa) and in two behavioral contexts (rest vs. cognitive co‐activation). Using accelerometry, we tested the effect of both interventions on tremor intensity and tremor variability.ResultsLevodopa significantly reduced tremor intensity (across behavioral contexts), while cognitive co‐activation increased it (across treatment conditions). Crucially, the levodopa effect was significantly smaller during cognitive co‐activation than during rest. Resting tremor variability increased after levodopa and decreased during cognitive co‐activation.ConclusionCognitive stress reduces the levodopa effect on Parkinson's tremor. This effect may be explained by a stress‐related depletion of dopamine in the basal ganglia motor circuit, by stress‐related involvement of nondopaminergic mechanisms in tremor (e.g., noradrenaline), or both. Targeting these mechanisms may open new windows for treatment. Clinical tremor assessments under evoked cognitive stress (e.g., counting tasks) may avoid overestimation of treatment effects in real life.

Dopamine controls Parkinson's tremor by inhibiting the cerebellar thalamus.

Parkinson's resting tremor is related to altered cerebral activity in the basal ganglia and the cerebello-thalamo-cortical circuit. Although Parkinson's disease is characterized by dopamine depletion in the basal ganglia, the dopaminergic basis of resting tremor remains unclear: dopaminergic medication reduces tremor in some patients, but many patients have a dopamine-resistant tremor. Using pharmacological functional magnetic resonance imaging, we test how a dopaminergic intervention influences the cerebral circuit involved in Parkinson's tremor. From a sample of 40 patients with Parkinson's disease, we selected 15 patients with a clearly tremor-dominant phenotype. We compared tremor-related activity and effective connectivity (using combined electromyography-functional magnetic resonance imaging) on two occasions: ON and OFF dopaminergic medication. Building on a recently developed cerebral model of Parkinson's tremor, we tested the effect of dopamine on cerebral activity associated with the onset of tremor episodes (in the basal ganglia) and with tremor amplitude (in the cerebello-thalamo-cortical circuit). Dopaminergic medication reduced clinical resting tremor scores (mean 28%, range -12 to 68%). Furthermore, dopaminergic medication reduced tremor onset-related activity in the globus pallidus and tremor amplitude-related activity in the thalamic ventral intermediate nucleus. Network analyses using dynamic causal modelling showed that dopamine directly increased self-inhibition of the ventral intermediate nucleus, rather than indirectly influencing the cerebello-thalamo-cortical circuit through the basal ganglia. Crucially, the magnitude of thalamic self-inhibition predicted the clinical dopamine response of tremor. Dopamine reduces resting tremor by potentiating inhibitory mechanisms in a cerebellar nucleus of the thalamus (ventral intermediate nucleus). This suggests that altered dopaminergic projections to the cerebello-thalamo-cortical circuit have a role in Parkinson's tremor.aww331media15307619934001.

Review of tremor in Parkinson's disease and atypical parkinsonian disorders

Rest tremor (RT), a cardinal feature of Parkinson's disease (PD) is often accompanied by other types of tremor such as action tremor, which includes postural tremor, kinetic tremor, re-emergent tremor (ReT), and orthostatic tremor (OT). Literature on other tremors of PD, especially ReT and OT, is scarce. Tremor can be present in any of the atypical parkinsonian disorders such as progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, and dementia with Lewy bodies. RT can even be the presenting symptom of these disorders. The objective of this review is to provide a comprehensive review of lesser known tremors in PD and to critically look at the prevalence of tremor in atypical Parkinsonian disorders.

Mutation Analysis of HTRA2 Gene in Chinese Familial Essential Tremor and Familial Parkinson's Disease.

Background. HTRA2 has already been nominated as PARK13 which may cause Parkinson's disease, though there are still discrepancies among these results. Recently, Gulsuner et al.'s study found that HTRA2 p.G399S is responsible for hereditary essential tremor and homozygotes of this allele develop Parkinson's disease by examining a six-generation family segregating essential tremor and essential tremor coexisting with Parkinson's disease. We performed this study to validate the condition of HTRA2 gene in Chinese familial essential tremor and familial Parkinson's disease patients, especially essential tremor. Methods. We directly sequenced all eight exons, exon-intron boundaries, and part of the introns in 101 familial essential tremor patients, 105 familial Parkinson's disease patients, and 100 healthy controls. Results. No exonic variant was identified, while one exon-intron boundary variant (rs2241028) and one intron variant (rs2241027) were detected, both with no clinical significance and uncertain function. There was no difference in allele, genotype, and haplotype between groups. Conclusions. HTRA2 exonic variant might be rare among Chinese Parkinson's disease and essential tremor patients with family history, and HTRA2 may not be the cause of familial Parkinson's disease and essential tremor in China.

In-Vitro Real-Time Coupled Electrophysiological and Electrochemical Signals Detection with Glassy Carbon Microelectrodes

The ability to carry out coupled and simultaneous electrical and electrochemical signals detection in the context of central and peripheral nervous systems has been of major research interest for sometimes now. This real-time capability could significantly help in developing more complete insight and understanding of the underlying mechanism of the interplay between electrical and neurotransmitter signals in neural communications at synapses, particularly in diseased states. Further, with increasing clinical interest in the use of electrical stimulation as therapeutic platform for variety of disease states from spinal cord injury to Parkinson's disease and essential tremor, there is pressing need for understanding the actual mechanism of its efficacy. In this study, therefore, we present an enabling platform that consists of a novel polymeric probe supported on a flexible substrate with microelectrode array specifically targeting simultaneous detection of neurotransmitters and electrophysiological signals. This probe consists of an array of patternable glassy carbon (GC) microelectrodes which have a superior electrochemical performance due to their wide electrochemical window and surface attachment chemistry tailorability along with excellent and stable conductivity. In this study, we report that these microelectrodes can detect – in real time – serotonin, a key neurotransmitter involved in mood and sleep regulations, in in-vitro environment within 25 nM - 1 μM concentration range with resolution of 25 nM while simultaneously recording ECoG (electrocorticography) electrical signals. The probes are also capable of stimulating at a current density of 2.5 A/cm2 (360 μA) and wide voltage range of at least −0.6 V to +1.2 V with remarkable stability.

REM-sleep behavior disorder and sleepwalking in a patient with Parkinson's disease and essential tremor

REM-sleep behavior disorder (RBD), a form of parasomnia, is characterized by motor and/or speech activity during sleep corresponding to the dream content. RBD is currently considered as a marker of onset of neurodegenerative diseases (sinucleinopathies) and as a most specific early symptom of Parkinson's disease (PD). The authors describe a clinical case of a patient with the combination of essential tremor, initial signs of PD and RBD. A polysomnographic study has confirmed clinical signs of RBD and determined the disturbances of sleep architecture: the increase in falling asleep, number of awakenings, wakefulness during sleep, the absence of deep slow-wave sleep. The particular features of the patient were essential tremor and sleep walking.

Refining diagnosis of Parkinson's disease with deep learning-based interpretation of dopamine transporter imaging.

Dopaminergic degeneration is a pathologic hallmark of Parkinson's disease (PD), which can be assessed by dopamine transporter imaging such as FP-CIT SPECT. Until now, imaging has been routinely interpreted by human though it can show interobserver variability and result in inconsistent diagnosis. In this study, we developed a deep learning-based FP-CIT SPECT interpretation system to refine the imaging diagnosis of Parkinson's disease. This system trained by SPECT images of PD patients and normal controls shows high classification accuracy comparable with the experts' evaluation referring quantification results. Its high accuracy was validated in an independent cohort composed of patients with PD and nonparkinsonian tremor. In addition, we showed that some patients clinically diagnosed as PD who have scans without evidence of dopaminergic deficit (SWEDD), an atypical subgroup of PD, could be reclassified by our automated system. Our results suggested that the deep learning-based model could accurately interpret FP-CIT SPECT and overcome variability of human evaluation. It could help imaging diagnosis of patients with uncertain Parkinsonism and provide objective patient group classification, particularly for SWEDD, in further clinical studies.

Nonmotor Symptoms in Essential Tremor and Other Tremor Disorders.

Tremor, like dystonia, is a term used at the phenomenological, syndromic, and aetiopathological level. Parkinsonian, essential, and dystonic tremor are the three most common tremor diagnoses encountered in clinical practice. Investigation of nonmotor symptoms in essential tremor and dystonic tremor syndromes is significantly hampered by the lack of clear clinical diagnostic criteria for these groups at a syndromic level, and the absence of biomarkers which allow definitive diagnosis at an aetiopathological level. Much work is needed in clarifying the motor features of these disorders in order to allow delineation of the nonmotor features of the most common tremor syndromes. With this limitation in mind, this chapter reviews what is known about nonmotor symptoms in these two tremor types. The final sections deal with nonmotor symptoms observed in patients with lesional tremor, thankfully a much more clearly defined albeit less common group of patients.

Differential Diagnosis of Parkinson Disease, Essential Tremor, and Enhanced Physiological Tremor with the Tremor Analysis of EMG.

We investigate the differential diagnostic value of tremor analysis of EMG on Parkinson's disease (PD), essential tremor (ET), and enhanced physiological tremor (EPT). Clinical data from 25 patients with PD, 20 patients with ET, and 20 patients with EPT were collected. The tremor frequency and muscle contraction pattern of the resting, posture, and 500 g and 1000 g overload were recorded. The frequency of PD tremor was 4–6 Hz, and the frequency of ET was also in this range; the frequency of EPT is 6–12 hz having some overlap with PD. The muscle contraction patterns of the ET and EPT group were mainly synchronous contraction, and the muscle contraction mode of the PD group was mainly alternating contraction. Having tremor latency from rest to postural position and having changes in tremor amplitude after mental concentration in PD might distinguish ET. Tremor analysis of EMG was able to distinguish PD from ET and EPT by varying the tremor frequency and muscle contraction pattern. It can also differentiate between PD and ET by the latency and concentration effect and ET and EPT by weight load effect.

Re-emergent tremor in Parkinson’s disease: Clinical and accelerometric properties

Re-emergent tremor (RET) and the classical parkinsonian rest tremor were considered as two different phenomena of the same central tremor circuit. However, clinical and accelerometric characteristics of these tremors were not previously compared in a single study. We evaluated disease characteristics and accelerometric measurements of two tremor types in 42 patients with Parkinson’s disease. Disease specific features and accelerometric measurements of peak frequency, amplitude at peak frequency and the root mean square (RMS) amplitude of two tremor types were compared. Eighteen patients had RET and the mean latency of the RET was 9.48 (±9.2)s. Groups of only rest tremor and RET did not differ significantly in age of disease onset, disease duration and severity and mean levodopa equivalent dose. Comparison of peak frequency and amplitude at peak frequency were not different between the groups, but RMS amplitude was significantly higher in the RET group (p=0.03). RMS amplitude of RET was also correlated with disease severity (r=.48, p=0.04). These results support the previous notion that rest tremor and RET are analogue, both are triggered by the same central ossilator with RET being only the suppression of the rest tremor due to arm repositioning.

Dopaminergic medication unrelated myoclonus is less related to tremor in idiopathic Parkinson's disease.

Myoclonus in Parkinson's disease (PD) may be related or unrelated to dopaminergic medication and may share some features of cortical myoclonus. The aim of this study was to analyze clinical and electrophysiological correlates of the dopaminergic treatment unrelated myoclonus in PD patients. We included 17 PD patients with the end-of-dose myoclonus and 16 PD patients without myoclonus between January 2010 and June 2011. Surface electromyography of upper extremity muscles and long latency reflexes (LLRs) were performed. Positive or negative myoclonus with a duration of 35-100ms was observed. Rest tremor was less frequent in the group with myoclonus. Only one PD patient with myoclonus had C reflex. Mean LLR amplitude was significantly high in PD with myoclonus compared to the group without myoclonus (p=0.024). Dopaminergic treatment unrelated myoclonus is less related to rest tremor in PD, may be positive or negative, and exhibits similar features to cortical myoclonus.

Research of hand tremor vibrations and interference with external me-chanical oscillations source

This paper presents the research of hand tremor vibrations and interference with external mechanical vibrations source. Photogrammetry were used to capture and analyze hand tremor parameters from 8 patient with essential and Parkinson tremors. Blood perfusion device, that creates mechanical vibrations, was used as an external source of mechanical vibrations and was tested with patients. Device interference with hand tremor showed promising results of hand tremor reduction. The minimum points had 16.5 % lower amplitude of hand tremor. The maximum amplitudes were about 50 % greater and these results show the compatibility of the method but the control algorithm needs to be improved. DOI: http://dx.doi.org/10.5755/j01.mech.22.5.16351

Evaluating the electrophysiological features of tremor in Parkinson's disease and essential tremor using accelerometry

Objective: To investigate the electrophysiological features of tremor intensity, frequency and frequency dispersion of Parkinsonian (PT group) and essential (ET group) tremors using accelerometry. Methods: The amplitude, frequency and frequency dispersion of rest tremor, postural tremor and the influence of weight on tremor of 35 PT patients and 40 ET patients in Department of Neurology, the Second Affiliated Hospital Zhejiang University School of Medicine from May 2015 to April 2016 were retrospectively analyzed and compared. Data of the more and less trembling hands were statistically elaborated. Results: In resting, postural and loading states, PT amplitudes of the less affected hand were smaller than the more affected one. The less affected hand were (147±32), (142±36), (157±40)μV, the more affected hand were (185±41), (164±29), (190±33)μV, respectively; ET amplitudes of the less affected hand were also smaller than the more affected one, and the less affected hand were (149±33), (157±33), (169±43)μV, the more affected hand were (176±39), (189±39), (213±36)μV, respectively; PT frequencies of the less affected hand were faster than the more affected one, with the less affected hand (6.1±1.1), (6.4±1.7), (6.5±2.0)Hz, the more affected hand (5.4±1.3), (5.5±1.1), (5.7±1.1)Hz, respectively, but ET frequencies of the less affected hand were similar to the more affected one, with the less affected hand (6.5±1.3), (7.0±1.2), (7.2±1.5)Hz, the more affected hand (7.0±1.0), (7.3±1.0), (7.6±1.1)Hz, respectively; in resting and postural states, PT frequency dispersions of the less affected hand were broader than the more affected one, the less affected hand were (2.1±0.6), (2.4±1.1)Hz, respectively; the more affected hand were (1.6±0.8), (1.7±0.9)Hz, respectively. But in loading state, PT frequency dispersions were similar in both sides (2.3±1.2, 2.2±1.1)Hz; In resting, postural and loading states, ET frequency dispersions were also similar in both two sides, the less affected hand were (2.0±1.1), (2.2±0.9), (1.9±1.0)Hz, the more affected hand were (1.8±0.6), (1.9±0.8), (2.1±0.7)Hz. Conclusions: Tremor intensity is significantly asymmetric both in PT and ET, while frequency and frequency dispersion are symmetric in ET but asymmetric in PT. Bilateral assessment of frequency related tremor parameters may be useful for differentiating ET from PT.

Gait and tremor assessment for patients with Parkinson’s disease using wearable sensors

Abstract Typically, subjects with Parkinson’s disease (PD) display instances of tremor at an early stage of the disease and later on develop gait impairments and postural instability. In this research, we have investigated the effect of using both gait and tremor features for an early detection and monitoring of PD. Various features were extracted from the data collected from the wearable sensors and further analyzed using statistical analysis and machine learning techniques to find the most significant features that would best distinguish between the two groups: subjects with PD and healthy control subjects. The analysis of our results shows that the features of step distance, stance and swing phases, heel and normalized heel forces contributed more significantly to achieving a better classification between the two groups in comparison with other features. Moreover, the tremor analysis based on the frequency-domain characteristics of the signal including amplitude, power distribution, frequency dispersion, and median frequency was carried out to identify PD tremor from atypical Parkinsonism tremor.

Resting-state functional connectivity of subthalamic nucleus in different Parkinson's disease phenotypes

Previous studies showed that the subthalamic nucleus (STN) plays a crucial role in Parkinson's disease (PD) pathophysiology. During rest, PD phenotypes exhibit different STN functional connectivity. STN functional connectivity was examined in 31 PD patients [12 tremor-dominant (TD) and 19 posture instability gait difficulty (PIGD)] and 22 healthy controls (HC). Compared with controls and PIGD patients, the TD patients exhibited higher functional connectivity between the bilateral STN and the left cerebellar anterior lobe. Compared with the TD and HC groups, in the PIGD subgroup functional connectivity was lower between the left putamen and the STN, as well as between the pons and the STN. In the PIGD subgroup, functional connectivity was greater between the STN and bilateral occipital lobe, which positively correlated with PIGD scores in PD patients. Additionally, STN-cerebellum connectivity positively correlated with the tremor score, and STN-putamen connectivity negatively correlated with the PIGD score in PD patients. PD subtypes with distinguished STN functional connectivity might explain the various pathophysiological mechanisms in tremor and gait disorders. Increased coupling between the STN and cerebellum might underlie the neural substrate of PD tremors. Lower functional connectivity between the STN and putamen might underpin PD gait and posture disturbances, while higher functional connectivity between the STN and visual cortex might play a compensatory role.

Mutation analysis of CHCHD2 gene in Chinese Han familial essential tremor patients and familial Parkinson's disease patients

CHCHD2 is the latest identified Parkinson's disease (PD)-causing gene, and previous studies have reported the same CHCHD2 variant (182C>T, Thr61Ile) in both PD and essential tremor (ET) patients. Whether CHCHD2 gene mutations are involved in both of these diseases remains unclear. We sequenced CHCHD2 gene in 171 familial ET patients, 133 autosomal dominant Parkinson's disease patients, and 211 normal controls. No pathogenic mutations were found, suggesting that CHCHD2 gene may not play a major role in our familial Chinese Han ET and PD patients.