Involuntary Oscillations Research Articles

Quantitative Analysis of Parkinsonian Tremor in a Clinical Setting Using Inertial Measurement Units.

Background Parkinson's disease (PD) is a neurodegenerative disorder that affects human voluntary movements. Tremor is one of the most common symptoms of PD and is expressed as involuntary oscillation of the body. Tremors can be analysed in the frequency domain. Objective The aim of the current study was to examine selected tremor parameters (frequency, root mean square, and approximated entropy) in order to quantify the characteristics of patients diagnosed with PD, compared to a healthy control group, and to compare the parameters by dividing the subjects according to UPDRS assessment. Methods The subjects were divided into two groups: a group of people diagnosed with PD (n = 19) and a control group consisting of healthy volunteers (CO = 12). Each subject performed motor tasks specific to certain tremors: the finger-to-nose test. Each subject performed a motor task three times. A nine degree of freedom (DOF) wireless inertial measurement unit was used for the measurement of upper limb motor tasks. For the quantitative estimation of kinetic and postural tremors, dominant frequency, root means square, and approximation entropy were selected and calculated from the measured angular velocity and linear acceleration signals. A one-way ANOVA with a significance level of α = 0.05 was used to test the null hypothesis that the means of the tremor metrics were the same between the PD and CO groups. Results Statistically significant differences between PD patients and control groups were observed in ApEn acceleration signal of kinetic tremor, ApEn angular velocity signal of kinetic tremor, ApEn angular velocity of postural tremor, frequency acceleration signal of postural tremor, and RMS angular speed kinetic tremor. Conclusion Application of inertial measurement units for clinical research of patients and PD tremor evaluation allows providing quantitative information for diagnostic purposes, during screening in a clinical setting that differentiates between PD patients and controls.

Saccadic oscillations in 4 dogs and 1 cat

Disorders affecting the control of saccadic eye movements result in involuntary saccadic oscillations and are widely reported in human medicine. Information regarding the occurrence and potential importance of saccadic oscillations in veterinary medicine is currently limited. The clinical histories of three dogs and one cat displaying involuntary eye movements consistent with opsoclonus are presented, with final diagnoses including idiopathic generalized tremor syndrome and neuronal ceroid lipofuscinosis (NCL). A dog with eye movements closely resembling macrosaccadic oscillations is also presented, for which a final diagnosis of NCL was made. All animals had clinical signs of cerebellar disease. As in human medicine, recognition of these forms of involuntary eye movement might suggest a cerebellar neuroanatomic localization. Opsoclonus and macrosaccadic oscillations are forms of involuntary saccadic eye movement that are both unrecognized and under‐reported in veterinary medicine.

FRMD7 variants associated with congenital nystagmus in Korea

Background: Congenital nystagmus (CN) is the involuntary oscillation of the eyes with onset in the first few months of life. CN can be an idiopathic disease (idiopathic infantile nystagmus, IIN) or can be a feature of other ocular diseases. The inheritance of CN are heterogenous, but the most common form is X-linked-IIN. FRMD7 resides at Xq26-27 and approximately 50% of X-linked IIN families map to this region. Currently, over 70 different mutations within FRMD7 have been reported.

Algorithm to demodulate an electromyogram signal modulated by essential tremor

Essential tremor is a disorder that causes involuntary oscillations in patients both while they are engaged in actions and when maintaining a posture. Such patients face serious difficulties in performing daily living activities such as meal movement. We have been developing an electromyogram (EMG)-controlled exoskeleton to suppress tremors to support the movements of these patients. The problem is that the EMG signal of the patients is modulated by the tremor signal as multiplicative noise. In this paper, we proposed a novel signal processing method to demodulate patients’ EMG signals. We modelled the multiplicative tremor signal with a powered sine wave and the tremor signal in the EMG signal was removed by dividing the modelled tremor signal into the EMG signal. To evaluate the effectiveness of the demodulation, we applied the method to a real patient’s EMG signal, extracted from biceps brachii while performing an elbow flexion. We quantified the effect of the demodulation by root mean square error between two kinds of muscle torques, an estimated torque from the EMG signal and calculated torque from inverse dynamics based on the motion data. The proposed method succeeded in reducing the error by approximately 15–45% compared with using a low-pass filter, typical processing for additive noise, and showed its effectiveness in the demodulation of the patients’ EMG signal.

From healthy to pathology through a fall in dynamical complexity of involuntary oscillations of the human hand

The task is to estimate quantitative features in involuntary oscillations of shaking (tremor) of fingers accompanied the performance of the motor task by healthy subjects, patients with Parkinson’ disease and individuals with the essential tremor. For solving the task the tremor patterns are examined by the wavelet-transform modulus maxima method and the recurrence quantification analysis. The physiological tremor is characterized by the minimal energy of the wavelet spectrum, the maximal degree of multifractality, the minimal degree of determinism and the maximal recurrence time density entropy, reflecting the greatest uncertainty of the period value. During the essential tremor the significant enhancement of the wavelet spectrum energy and the decrease of the dynamical complexity of involuntary oscillations are observed. It is evident as the fall in the multifractality degree, the growth of determinism in recurrence plots, the decrease of the recurrence time density entropy and the emergence of unstable periodic orbits in involuntary oscillations. For the parkinsonian tremor all the trends are enhanced that lead to more definite dynamics of patterns. Therefore, our results demonstrate that the dynamical complexity of patterns of involuntary oscillations decreases in larger degree for Parkinson’ disease, than for patients with the syndrome of the essential tremor, that is, it declines with increasing the severity degree of motor disorders. The results obtained for the first time can be applied for evaluating the degree of deviation of the motor function from the healthy one.

Exaggerated haemodynamic and neural responses to involuntary contractions induced by whole-body vibration in normotensive obese versus lean women.

What is the central question of this study? In obesity, the exaggerated blood pressure response to voluntary exercise is linked to hypertension, yet the mechanisms are not fully elucidated. We examined whether involuntary contractions elicit greater haemodynamic responses and altered neural control of blood pressure in normotensive obese versus lean women. What is the main finding and its importance? During involuntary contractions induced by whole-body vibration, there were augmented blood pressure and spontaneous baroreflex responses in obese compared with lean women. This finding is suggestive of an overactive mechanoreflex in the exercise-induced hypertensive response in obesity. Passive contractions did not elicit differential heart rate responses in obese compared with lean women, implying other mechanisms for the blunted heart rate response reported during voluntary exercise in obesity. In obesity, the exaggerated blood pressure (BP) response to exercise is linked to hypertension, yet the mechanisms are not fully elucidated. In this study, we examined whether involuntary mechanical oscillations, induced by whole-body vibration (WBV), elicit greater haemodynamic responses and altered neural control of BP in obese versus lean women. Twenty-two normotensive, premenopausal women (12 lean and 10 obese) randomly underwent a passive WBV (25Hz) and a control protocol (similar posture without WVB). Beat-by-beat BP, heart rate, stroke volume, systemic vascular resistance, cardiac output, parasympathetic output (evaluated by heart rate variability) and spontaneous baroreceptor sensitivity (sBRS) were assessed. We found that during WBV, obese women exhibited an augmented systolic BP response compared with lean women that was correlated with body fat percentage (r = 0.77; P<0.05). The exaggerated BP rise was driven mainly by the greater increase in cardiac output index in obese versus lean women, associated with a greater stroke volume index in obese women. Involuntary contractions did not elicit a differential magnitude of responses in heart rate, heart rate variability indices and systemic vascular resistance in obese versus lean women; however, they did result in greater sBRS responses (P<0.05) in obese women. In conclusion, involuntary contractions elicited an augmented BP and sBRS response in normotensive obese versus lean women. The greater elevations in circulatory haemodynamics in obese women are suggestive of an overactive mechanoreflex in the exercise-induced hypertensive response in obesity.

Molecular genetic analysis of patients with sporadic and X-linked infantile nystagmus

ObjectivesInfantile nystagmus (IN) is a genetically heterogeneous condition characterised by involuntary rhythmic oscillations of the eyes accompanied by different degrees of vision impairment. Two genes have been identified as mainly...

A previously unidentified deletion in G protein-coupled receptor 143 causing X-linked congenital nystagmus in a Chinese family.

Background:Congenital nystagmus (CN) is characterized by conjugated, spontaneous, and involuntary ocular oscillations. It is an inherited disease and the most common inheritance pattern is X-linked CN. In this study, our aim is to identify the disease-causing mutation in a large sixth-generation Chinese family with X-linked CN.Methods:It has been reported that mutations in four-point-one, ezrin, radixin, moesin domain-containing 7 gene (FRMD7) and G protein-coupled receptor 143 gene (GPR143) account for the majority patients of X-linked nystagmus. We collected 8 ml blood samples from members of a large sixth-generation pedigree with X-linked CN and 100 normal controls. FRMD7 and GPR143 were scanned by polymerase chain reaction (PCR)-based DNA sequencing assays, and multiplex PCR assays were applied to detect deletions.Results:We identified a previously unreported deletion covering 7 exons in GPR143 in a Chinese family. The heterozygous deletion from exon 3 to exon 9 of GPR143 was detected in all affected males in the family, while it was not detected in other unaffected relatives or 100 normal controls.Conclusions:This is the first report of molecular characterization in GPR143 gene in the CN family. Our results expand the spectrum of GPR143 mutations causing CN and further confirm the role of GPR143 in the pathogenesis of CN.

Contribution of inter-muscular synchronization in the modulation of tremor intensity in Parkinson's disease.

BackgroundInvoluntary central oscillations at single and double tremor frequencies drive the peripheral neuromechanical system of muscles and joints to cause tremor in Parkinson’s disease (PD). The central signal of double tremor frequency was found to correlate more directly to individual muscle EMGs (Timmermann et al. 2003). This study is aimed at investigating what central components of oscillation contribute to inter-muscular synchronization in a group of upper extremity muscles during tremor in PD patients.Methods11 idiopathic, tremor dominant PD subjects participated in this study. Joint kinematics during tremor in the upper extremity was recorded along with EMGs of six upper arm muscles using a novel experimental apparatus. The apparatus provided support for the upper extremity on a horizontal surface with reduced friction, so that resting tremor in the arm can be recorded with a MotionMonitor II system. In each subject, the frequencies of rhythmic firings in upper arm muscles were determined using spectral analysis. Paired and pool-averaged coherence analyses of EMGs for the group of muscles were performed to correlate the level of inter-muscular synchronization to tremor amplitudes at shoulder and elbow. The phase shift between synchronized antagonistic muscle pairs was calculated to aid coherence analysis in the muscle pool.ResultsRecorded EMG revealed that rhythmic firings were present in most recorded muscles, which were either synchronized to form phase-locked bursting cycles at a subject specific frequency, or unsynchronized with a random phase distribution. Paired coherence showed a stronger synchronization among a subset of recorded arm muscles at tremor frequency than that at double tremor frequency. Furthermore, the number of synchronized muscles in the arm was positively correlated to tremor amplitudes at elbow and shoulder. Pool-averaged coherence at tremor frequency also showed a better correlation with the amplitude of resting tremor than that of double tremor frequency, indicating that the neuromechanical coupling in peripheral neuromuscular system was stronger at tremor frequency.ConclusionsBoth paired and pool-averaged coherences are more consistent indexes to correlate to tremor intensity in a group of upper extremity muscles of PD patients. The central drive at tremor frequency contributes mainly to synchronize peripheral muscles in the modulation of tremor intensity.

Ocular Flutter associated with Merkel Cell Carcinoma

Ocular flutter is a relatively rare eye movement disorder that refers to occasional bursts of involuntary horizontal oscillation around the point of fixation, characterized by rapid, repetitive, horizontal, symmetrical and sinusoidal oscillation without inter- saccadic interval. It is known to be associated with disorders of the cerebellum and brainstem resulting from various pathological conditions, but it's anatomical and pathophysiological basis remains unclear. Here, we present the case of a patient who had severe ocular flutter associated with Merkel cell carcinoma. Key Words: Ocular flutter, Merkel cell carcinoma, Paraneoplastic syndrome

A start codon mutation of the FRMD7 gene in two Korean families with idiopathic infantile nystagmus.

Idiopathic infantile nystagmus (IIN) is the involuntary oscillation of the eyes with onset in the first few months of life. The most common form of inheritance is X-linked, and mutations in FRMD7 gene are a major cause. To identify the FRMD7 gene mutations associated with X-linked IIN, we performed PCR-based DNA direct sequencing in 4 affected subjects from 2 Korean families. We also assessed structural abnormalities of retina and optic nerve head using optical coherence tomography (OCT). Genetic analysis revealed a A>G transversion at nucleotide c.1, the first base of the start codon. This mutation leads to the loss of the primary start codon ATG for methionine, which is replaced by a triplet GTG for valine. The alternative in-frame start codon is not present around a mutation. OCT revealed the morphological changes within the optic nerve head, including shallow cup depth and small cup-to-disc ratio. In summary, we identified a novel start codon mutation within the FRMD7 gene of 2 Korean families. Our data expands the mutation spectrum of FRMD7 causing IIN. We also demonstrated abnormal developments of afferent system in patients with FRMD7 mutations using OCT, which may help to understand the etiological factor in development of nystagmus.

A novel mutation in FRMD7 causes X-linked idiopathic congenital nystagmus in a North Indian family

Idiopathic congenital nystagmus (ICN) is the most common form of oculomotor disorder characterized by involuntary bilateral ocular oscillations. Primarily the disease is an ocular anomaly but the pathophysiology is associated with neuronal cytoskeletal dynamics in the brain. In the current study, a three generation North Indian family affected with X-linked idiopathic congenital nystagmus (XLICN) was recruited. Our aim was to identify the causal mutation for ICN in the family by screening the candidate gene, FERM domain containing-7 (FRMD7). This gene has been implicated in XLICN as it regulates neuronal cytoskeletal proteins and neurite outgrowth in the developing brain. Therefore, the entire protein coding region, including splice junctions, 5′ UTR and 3′ UTR of FRMD7 was screened by PCR-Sanger sequencing. Targeted sequencing revealed a novel A to G transition in the exon seven (c.556A>G), resulting in a conservative substitution of methionine by valine at codon 186 (p.M186V). A cohort of healthy individuals was also checked for presence of the putative causal variant by allele specific PCR. All the affected males and carriers in the family shared this variant; however, this was absent in the unaffected males as well as 100 unrelated healthy individuals. Further, protein homology modeling revealed that the change p.M186V might destabilize the interaction between the FERM-M and FERM-C domains. The in silico prediction supports pathogenicity of the mutation; nevertheless it needs in vivo validation in the future. This is the first genetic investigation of XLICN in a North Indian family where we report a novel causal mutation c.556A>G (p.M186V) in the gene FRMD7.

Quick phases of infantile nystagmus show the saccadic inhibition effect.

Infantile nystagmus (IN) is a pathological, involuntary oscillation of the eyes consisting of slow, drifting eye movements interspersed with rapid reorienting quick phases. The extent to which quick phases of IN are programmed similarly to saccadic eye movements remains unknown. We investigated whether IN quick phases exhibit 'saccadic inhibition,' a phenomenon typically related to normal targeting saccades, in which the initiation of the eye movement is systematically delayed by task-irrelevant visual distractors. We recorded eye position from 10 observers with early-onset idiopathic nystagmus while task-irrelevant distractor stimuli were flashed along the top and bottom of a large screen at ±10° eccentricity. The latency distributions of quick phases were measured with respect to these distractor flashes. Two additional participants, one with possible albinism and one with fusion maldevelopment nystagmus syndrome, were also tested. All observers showed that a distractor flash delayed the execution of quick phases that would otherwise have occurred approximately 100 ms later, exactly as in the standard saccadic inhibition effect. The delay did not appear to differ between the two main nystagmus types under investigation (idiopathic IN with unidirectional and bidirectional jerk). The presence of the saccadic inhibition effect in IN quick phases is consistent with the idea that quick phases and saccades share a common programming pathway. This could allow quick phases to take on flexible, goal-directed behavior, at odds with the view that IN quick phases are stereotyped, involuntary eye movements.

The gait disorder in downbeat nystagmus syndrome.

BackgroundDownbeat nystagmus (DBN) is a common form of acquired fixation nystagmus with key symptoms of oscillopsia and gait disturbance. Gait disturbance could be a result of impaired visual feedback due to the involuntary ocular oscillations. Alternatively, a malfunction of cerebellar locomotor control might be involved, since DBN is considered a vestibulocerebellar disorder.MethodsInvestigation of walking in 50 DBN patients (age 72±11 years, 23 females) and 50 healthy controls (HS) (age 70±11 years, 23 females) using a pressure sensitive carpet (GAITRite). The patient cohort comprised subjects with only ocular motor signs (DBN) and subjects with an additional limb ataxia (DBNCA). Gait investigation comprised different walking speeds and walking with eyes closed.ResultsIn DBN, gait velocity was reduced (p<0.001) with a reduced stride length (p<0.001), increased base of support (p<0.050), and increased double support (p<0.001). Walking with eyes closed led to significant gait changes in both HS and DBN. These changes were more pronounced in DBN patients (p<0.001). Speed-dependency of gait variability revealed significant differences between the subgroups of DBN and DBNCA (p<0.050).Conclusions(I) Impaired visual control caused by involuntary ocular oscillations cannot sufficiently explain the gait disorder. (II) The gait of patients with DBN is impaired in a speed dependent manner. (III) Analysis of gait variability allows distinguishing DBN from DBNCA: Patients with pure DBN show a speed dependency of gait variability similar to that of patients with afferent vestibular deficits. In DBNCA, gait variability resembles the pattern found in cerebellar ataxia.

Individual larvae of the zebrafish mutant belladonna display multiple infantile nystagmus-like waveforms that are influenced by viewing conditions.

Infantile nystagmus syndrome (INS) is characterized by involuntary eye oscillations that can assume different waveforms. Previous attempts to uncover reasons for the presence of several nystagmus waveforms have not led to a general consensus in the community. Recently, we characterized the belladonna (bel) zebrafish mutant strain, in which INS-like ocular motor abnormalities are caused by misprojection of a variable fraction of optic nerve fibers. Here we studied intrinsic and extrinsic factors influencing the occurrence of different waveforms in bel larvae. Eye movements of bel larvae were recorded in the presence of a stationary grating pattern. Waveforms of spontaneous oscillations were grouped in three categories: "pendular," "unidirectional jerk," and "bidirectional jerk," and the occurrences of each category were compared within and between individual larvae. Moreover, the effects of the characteristics of a preceding optokinetic response (OKR), of the field of view, and of the eye orbital position were analyzed. The different waveform categories co-occurred in most individuals. We found waveforms being influenced by the preceding OKR and by the field of view. Moreover, we found different kinds of relationships between orbital position and initiation of a specific waveform, including pendular nystagmus in a more eccentric orbital position, and differences among jerk oscillations regarding the beating direction of the first saccade or waveform amplitude. Our data suggest that waveform categories in bel larvae do not reflect the severity of the morphological phenotype but rather are influenced by viewing conditions.

The interplay of eye movements and gait in patients with downbeat nystagmus syndrome

Downbeat nystagmus (DBN) is the most common form of acquired fixation nystagmus. The key symptom is vertical oscillopsia caused by involuntary eye movements. The patients also complain of instability of gait; however, the characteristics of gait disturbance are largely unknown. Gait disturbance could be a result of impaired visual feedback due to the involuntary ocular oscillations. Alternatively, a malfunction of cerebellar locomotor control might be involved, since DBN is considered a vestibulocerebellar disorder.

A new method for quantitative tremor assessment in sports

BackgroundThe physiological tremor consists in an involuntary oscillation of the limbs, in the range of 10 Hz, which is generated in part from supraspinal brain structures. Its quantitative assessment in the sport science is relevant for sports requiring ability and for the assessment of fatigue. However, the measurement of tremor is not yet entered in standard sports medicine practice because expensive and complex instrumentations are needed. We present a simple, compact and cost-effective device for tremor measurement, based on the remote of the Wii console, the Wiimote, a wirless triaxial accelerometer which can communicate via bluetooth with a personal computer. Materials and MethodsEight male healthy volunteers were asked to maintain with the dominant hand the Wiimote pointing a fixed target for for a minimum of 90 seconds. The conversion of bluetooth data sent by the Wiimote in a final file containing the accelerometer informations has been obtained using a custom script in GlovePie environment. The analysis of the predominant frequency band was done in R environment. We then demonstrated the sensibility of the Wiimote to the modification of tremor induced by a muscular exercise, analyzing tremor after 20 repetitions, at the maximum velocity of full range elbow extension/flexion exercises. Moreover, we compared the analysis of tremor using the Wiimote with two other widely used approaches, spiralometry and laser pointing. ResultsUsing the Wiimote it is possible to get a real time feedback on hand tremor. The sampling rate was sufficient to observe the frequency peak at 8-10 Hz, which characterizes postural tremor and the increase of tremor intensity after the exercise. Moreover the Wiimote largely outperformed the spiralometry and laser pointing system. ConclusionsThe Wii remote application represents an accessible and simple way for clinicians to quantify tremor which might easily become part of the standard toolkit for scientists and sports medicine professionals.

Development of an Exoskeleton to Support Eating Movements in Patients with Essential Tremor

Essential tremor is a disorder that causes involuntary oscillations in patients both while they are engaged in actions and when maintaining a posture. Such patients face serious difficulties in performing such daily living activities as eating, drinking, and writing. We have been developing an electromyogram-controlled exoskeleton to suppress tremors and support the eating movements of these patients. This exoskeleton is designed to suppress tremors and support voluntary movement at the elbow in terms of flexion and extension: movement of the elbow is essential in eating movements. In this study, we examined the effectiveness of our prototype exoskeleton at suppressing tremors. Our goal was to answer two questions: To what extent are the oscillations suppressed when wearing the exoskeleton? Is the exoskeleton able to suppress the oscillations sufficiently to allow eating movements? We were able to confirm experimentally that our exoskeleton can effectively suppress tremors to support eating movements.

Stress and Visual Function in Infantile Nystagmus Syndrome

Infantile nystagmus syndrome (INS) is an involuntary oscillation of the eyes that has been reported to impair vision and worsen under stress. This investigation aimed to measure visual function in terms of visual acuity (VA) and response time (RT), when INS subjects are placed under stress. A total of 23 subjects with INS and 20 control subjects performed a 2-alternative forced choice (2AFC) staircase procedure identifying the gap in a Landolt C, under 4 experimental conditions: initial acclimatization (A); task demand (TD), during which subjects received a small electrical shock for every incorrect answer; anticipatory anxiety (AA), during which subjects received a small shock at random intervals; and relaxed (R). Arousal was monitored with galvanic skin conductance (SkC). In addition to VA and eye movements, RTs were recorded. The SkC was higher in the TD and AA periods and lower during A and R. Shock significantly increased nystagmus amplitude (P < 0.01) and intensity (P < 0.007), and reduced foveation periods (FPs, P < 0.022). In both groups, VA was not reduced, but showed a slight improvement. However, shock increased RT (P < 0.009), and INS subjects were slower than controls (P < 0.0005). Increased arousal ("stress") provoked more intense nystagmus eye movements. As seen in other studies, stress did not reduce VA despite the shorter FPs. Although VA and FP can correlate across subjects, there would appear to be little correlation, if any, within a subject. However, RTs did increase with stress and shorter FPs, which may have an adverse impact on the visual performance of those with INS.

The Effect of Colored Overlays on Reading Performance in Infantile Nystagmus

Infantile nystagmus (IN) is an involuntary oscillations of the eyes with onset within 6 months from birth. It can result in vision loss owing to constant retinal motion and lead to significant psychosocial problems.1 Recent studies have described reading deficits associated with IN and found that they can be relatively mild under optimal reading conditions, but are more apparent when reading smaller font sizes.2 Colored overlays have been tested in numerous diseases for improving reading performance but not in IN.