Involuntary Oscillations Research Articles

FMRI and gene therapy in adults with CNGB3 mutation

Achromatopsia is an inherited retinal disease that affects 1 in 30,000–50,000 individuals and is characterised by an absence of functioning cone photoreceptors from birth. This results in severely reduced visual acuity, no colour vision, marked sensitivity to light and involuntary oscillations of the eyes (nystagmus). In most cases, a single gene mutation prevents normal development of cone photoreceptors, with mutations in the CNGB3 or CNGA3 gene being responsible for ∼80 % of all patients with achromatopsia. There are a growing number of studies investigating recovery of cone function after targeted gene therapy. These studies have provided some promise for patients with the CNGA3 mutation, but thus far have found limited or no recovery for patients with the CNGB3 mutation. Here, we developed colour-calibrated visual stimuli designed to isolate cone photoreceptor responses. We combined these with adapted fMRI techniques and pRF mapping to identify if cortical responses to cone-driven signals could be detected in 9 adult patients with the CNGB3 mutation after receiving gene therapy. We did not detect any change in brain activity after gene therapy when the 9 patients were analysed as a group. However, on an individual basis, one patient self-reported a change in colour perception, corroborated by improved performance on a psychophysical task designed to selectively identify cone function. This suggests a level of cone sensitivity that was lacking pre-treatment, further supported by a subtle but reliable change in cortical activity within their primary visual cortex.

Erroneous Compensation for Long-Latency Feedback Delays as Origin of Essential Tremor.

Essential tremor (ET), a movement disorder characterized by involuntary oscillations of the limbs during movement, remains to date not well understood. It has been recently suggested that the tremor originates from impaired delay compensation, affecting movement representation and online control. Here we tested this hypothesis directly with 24 ET patients (14 female; 10 male) and 28 neurologically intact (NI) human volunteers (17 female; 11 male) in an upper limb postural perturbation task. After maintaining their hand in a visual target, participants experienced perturbations of unpredictable direction and magnitude and were instructed to counter the perturbation and steer their hand back to the starting position. In comparison with NI volunteers, ET patients' early muscular responses (short and long-latency responses, 20-50 and 50-100 ms, respectively) were preserved or even slightly increased. However, they exhibited perturbation-dependent deficits when stopping and stabilizing their hand in the final target supporting the hypothesis that the tremor was generated by the feedback controller. We show in a computational model that errors in delay compensation accumulating over time produced the same small increase in initial feedback response followed by oscillations that scaled with the perturbation magnitude as observed in ET population. Our experimental results therefore validate the computational hypothesis that inaccurate delay compensation in long-latency pathways could be the origin of the tremor.

Impairments of saccadic and reaching adaptation in essential tremor are linked to movement execution.

Essential tremor (ET) is a neurological disorder characterized by involuntary oscillations of the limbs. Previous studies have hypothesized that ET is a cerebellar disorder and reported impairments in motor adaptation. However, recent advances have highlighted that motor adaptation involves several components linked to anticipation and control, all dependent on cerebellum. We studied the contribution of both components in adaptation to better understand the adaptation impairments observed in ET from a behavioral perspective. To address this question, we investigated behavioral markers of adaptation in ET patients (n = 20) and age-matched neurologically intact volunteers (n = 20) in saccadic and upper limb adaptation tasks, probing compensation for target jumps and for velocity-dependent force fields, respectively. We found that both groups adapted their movements to the novel contexts; however, ET patients adapted to a lesser extent compared with neurologically intact volunteers. Importantly, components of the movement linked to anticipation were preserved in the ET group, whereas components linked to movement execution appeared responsible for the adaptation deficit in this group. Altogether, our results suggest that execution deficits may be a specific functional consequence of the alteration of neural pathways associated with ET.NEW & NOTEWORTHY We tested essential tremor patients' adaptation abilities in classical tasks including saccadic adaptation to target jumps and reaching adaptation to force field disturbances. Patients' adaptation was present but impaired in both tasks. Interestingly, the deficits were mainly present during movement execution, whereas the anticipatory components of movements were similar to neurologically intact volunteers. These findings reinforce the hypothesis of a cerebellar origin for essential tremor and detail the motor adaptation impairments previously found in this disorder.

NYSTAGMUS IN CHILDHOOD: A SYSTEMATIC REVIEW

Nystagmus is an involuntary rhythmic oscillation of the eyes that results in decreased visual acuity owing to the excessive motion of pictures on the retina. This is because nystagmus causes the eyes to move in a repetitive pattern. It is of the utmost importance to differentiate infantile nystagmus from acquired nystagmus. In order to accomplish this, it is necessary to take into consideration not only the time at which the nystagmus first appeared, but also the features of its waveform. Oscillations of the eyes that are involuntary, often conjugate, and frequently rhythmic are referred to as nystagmus. Infantile nystagmus syndrome (INS) is the condition that accounts for the majority of cases of nystagmus in children. Because this ailment can last a person's entire life, it is essential that they are familiar with all of the treatment choices that are at their disposal. The primary foci of this review are the underlying etiology of nystagmus, the psychosocial and functional implications of nystagmus, and the current methods of treatments, which include optical, pharmacological, surgical, and rehabilitative treatment approaches. At this time, the brain mechanisms that are responsible for INS are not completely known. The evidence is limited to mostly pre- and post-study designs, and there are few objective comparisons of treatment procedures. The treatment choices are meant to increase the foveation length or correct abnormal head positions. Individualized management of INS should be implemented. The patient and the patient's physician are the ones who should make the decision regarding which treatment will be most beneficial for the patient in question.

Micro chromosomal deletions at the NYS7 locus and autosomal dominant nystagmus

Nystagmus is an ocular condition characterized by bilateral involuntary ocular oscillation which can severely affect vision. When not associated with other ocular or systemic diseases, it is referred to as idiopathic or congenital motor nystagmus (CMN). Genome-wide linkage studies have previously identified several loci associated with CMN, however the genes responsible for some of these loci have yet to be identified. We have examined a large, five-generation family with autosomal dominant CMN. Our purpose was to characterize the clinical manifestations and reveal the molecular basis of the disease in this family. In addition to full ophthalmic examination and imaging, molecular analysis included copy number variation analysis, linkage studies, and Sanger sequencing. Expression analyses of candidate genes was done by real-time PCR. Of the 68 family members, 27 subjects in five-generations had CMN, in line with an autosomal dominant inheritance pattern. Molecular analysis was performed on 27 members, 15 of them affected by CMN. Copy number variation analysis using array comparative genomic hybridization (aCGH) revealed a novel deletion located on 1q32 (NYS7) among affected individuals. Linkage analysis using polymorphic markers demonstrated full segregation with a heterozygous haplotype in all affected patients, with a LOD score of >5. Sanger sequencing of affected subjects revealed a novel deletion of 732,526 bp in the linkage interval. No protein-coding genes exist within the deleted region; however, the deletion disrupts topologically associated domains encompassing the gene NR5A2 and the non-protein coding MIR181A. Both are strongly associated with other genes expressed in the retina such as PROX1, which in turn is also associated with genes related to nystagmus such as PAX6. We therefore hypothesized that the deletion might affect NR5A2 and MIR181A expression, causing CMN. Expression analysis by real-time PCR showed significantly lower expression of NR5A2, and significantly higher expression of PROX1 among patients compared with controls. To conclude, among a large five-generation family with autosomal dominant CMN, a large deletion in the interval of NYS7 was linked with the disease. No protein-coding genes exist inside the deleted region, and so the exact mechanism in which CMN is caused is uncertain. Based on topological association and expression analyses we suggest a possible mechanism for the pathogenesis.

The Developmental Eye Movement Test Does Not Detect Oculomotor Problems: Evidence from Children with Nystagmus.

SIGNIFICANCEThe Developmental Eye Movement (DEM) test, a test purported to assess oculomotor skills, does not detect eye movement disorder in nystagmus syndromes. The test should not be used for the clinical evaluation of oculomotor disorders.PURPOSEThe DEM test ratio compares a horizontal number naming subtest with a vertical one to identify oculomotor problems independent of a child's visual-verbal naming skills. Here, we tested the construct validity of this method by comparing scores of children with and without pathologic nystagmus. Such a nystagmus disturbs normal fixation and saccadic behavior because of the presence of involuntary rhythmic oscillations of the eyes. Therefore, if the ratio is indeed a comprehensive measure of oculomotor problems, children with nystagmus should show an increased ratio score.METHODSThe DEM test performances of normally sighted children (n = 94), children with ocular visual impairments (VIo; n = 33), and children with cerebral visual impairment (n = 30) were analyzed using linear regression. Part of the children with VIo and cerebral visual impairment had either fusion maldevelopment nystagmus syndrome (n = 8) or infantile nystagmus syndrome (n = 20), whereas the others showed no pathologic nystagmus.RESULTSThe times needed for the horizontal and vertical subtests were significantly different between children with normal vision, VIo, and cerebral visual impairment (P < .001). However, the presence of nystagmus did not add significantly to the horizontal and vertical times (P > .20), nor did it have an effect on the ratio (P > .10).CONCLUSIONSThe DEM test ratio is not sensitive to fixation and saccade abnormalities associated with nystagmus, indicating that it does not have general construct validity to detect true eye movement disorders. Although not suitable for the evaluation of oculomotor disorders, the subtests do have clinical relevance in the diagnosis of cerebral visual impairment.

The Electrophysiological Perspectives of Essential, Enhanced Physiological, and Physiological Tremors

Abstract: Background: The most frequent movement issue seen in clinical practice is tremors. It is known as repetitive, involuntary oscillations. The diagnostic process for tremor patients can be time-consuming and complicated, as the identification of “Essential Tremor” and its distinction from other types of tremor. Objectives: This study aimed to describe the electrophysiological findings of essential, enhanced physiological, and physiological tremors, using surface electromyography and an accelerometer. Patients and Methods: The study included 24 patients with essential tremors, 10 patients with enhanced physiological tremors, and 10 patients with physiological tremors. We assessed the frequency, amplitude, and muscular contraction pattern of tremors during rest, posture, and a 1 kg load. Results: The tremor frequency of essential tremor patients was about 4.2-10.1 Hertz, while enhanced physiological tremor and physiological tremor were increased to 6.1–12.7 Hertz and 5.1-10.2 Hertz, respectively. The essential tremor group muscle contraction pattern was predominantly synchronous, as do all enhanced physiological, and physiological tremor patients, but with more fine low amplitude muscle bursts. By varying the tremor frequency and the weight load effect, tremor analysis could discriminate essential from enhanced physiological, and physiological tremors. Conclusions: The tremor analysis using surface electromyography and an accelerometer is sufficient to differentiate between essential tremors, enhanced physiological tremors, and physiological tremors.

Benchmark Device To Mitigate Jaw Tremor Using Gyroscopic Effect

A tremor is a mildly rhythmic muscle contraction and relaxation that predominantly involves involuntary oscillations or twitching movements of one’s body parts. Jaw tremor looks more like shivering although with different amplitude and frequency which can vary. Jaw tremors hinder patients’ day to day activities and hamper confidence, causing social handicaps. There are only drug-based solutions for jaw tremors to date. Currently, there are some surgical treatments like Deep Brain Stimulation (DBS), but, they have side effects. Our solution - the palliator a wearable, ergonomic device that dampens jaw tremors without producing any side effects on patients. The proposed solution uses two accelerometers to detect and distinguish involuntary tremors from the voluntary jaw motion and then uses the gyroscopic principle to control the involuntary motion, thus resisting the tremors.

Study of variability in tremor in Parkinson's Disease population

Objective: Tremor predominant Parkinson's Disease is often characterized by prominent tremor in at least one limb with relatively less significant rigidity and bradykinesia. Tremor is an involuntary oscillation of the body and as such is very disabling. The first line medication is very effective in controlling the tremor. The objective of the study is to measure the improvement in tremor after giving the medication.

Neural Representations of the Voice Tremor Spectrum.

Voice tremor is a common movement disorder that manifests as involuntary oscillations of laryngeal muscles, leading to rhythmic alterations in voice pitch and loudness. Differential diagnosis of essential tremor of voice (ETv) is often challenging and includes dystonic tremor of voice (DTv), which is characterized by irregular, isometric contractions of laryngeal muscles during dystonic activity. Although clinical characteristics of voice tremor are well described, the pathophysiology underlying its heterogeneous phenomenology remains limited. We used a multimodal approach of functional magnetic resonance imaging for assessment of brain activity during symptomatic speech production, high-resolution magnetic resonance imaging for the examination of cortical thickness and gray matter volume, and diffusion-weighted imaging for evaluation of white matter integrity to identify disorder-specific neural alterations and their relationships with the symptomatology of ETv and DTv. We found a broad overlap between cortical alterations in ETv and DTv, involving sensorimotor regions responsible for the integration of multisensory information during speech production, such as primary sensorimotor, inferior/superior parietal, and inferior temporal cortices. In addition, ETv and DTv showed unique patterns of abnormalities in regions controlling speech motor preparation, which were localized in the cerebellum in ETv and the premotor cortex, insula, and superior temporal gyrus in DTv. Neural alterations in superior parietal and inferior temporal cortices were correlated with ETv severity, whereas changes in the left premotor cortex were associated with DTv severity. Our findings point to the pathophysiological spectrum underlying ETv and DTv and favor a more heterogeneous rather than dichotomous diagnostic classification of these voice tremor disorders. © 2020 International Parkinson and Movement Disorder Society.

Management of nystagmus in children: a review of the literature and current practice in UK specialist services.

Nystagmus is an eye movement disorder characterised by abnormal, involuntary rhythmic oscillations of one or both eyes, initiated by a slow phase. It is not uncommon in the UK and regularly seen in paediatric ophthalmology and adult general/strabismus clinics. In some cases, it occurs in isolation, and in others, it occurs as part of a multisystem disorder, severe visual impairment or neurological disorder. Similarly, in some cases, visual acuity can be normal and in others can be severely degraded. Furthermore, the impact on vision goes well beyond static acuity alone, is rarely measured and may vary on a minute-to-minute, day-to-day or month-to-month basis. For these reasons, management of children with nystagmus in the UK is varied, and patients report hugely different experiences and investigations. In this review, we hope to shine a light on the current management of children with nystagmus across five specialist centres in the UK in order to present, for the first time, a consensus on investigation and clinical management.

Evaluating the impact of information and support for people with nystagmus in the digital age: A patient and carer questionnaire study

ABSTRACTBackground: Nystagmus is a disorder of rhythmic, involuntary oscillations of the eyes and can be classified as either infantile or acquired. Whether it occurs in isolation or as a part of other visual or neurological disorders, it causes significant visual dysfunction and problems with social functioning. In this study, we seek to understand ways in which people with nystagmus are currently supported across the UK and identify any geographical variations or disconnects between current practice and best practice, as judged by patients and their carers.Methods: A nationwide, qualitative, cross-sectional, questionnaire study of people with nystagmus and their carers. Recruitment was achieved through specialist clinics, charity events, online advertisements and social media calls. Data was gathered using five, age-appropriate questionnaires which were completed and returned to the research team between November 2016 and August 2018.Results: 184 respondents were included (89 carers, 47 patients aged 4–10 years, 5 aged 11–14 years, 4 aged 15–17 years and 39 > 18 years). Notably, respondents rated social media as the best source of information they have received, even compared with face-to-face consultation with medical professionals. Additionally, only 33% of the respondents had been offered visual impairment support. Notably, patterns of clinical practice and patient experience emerged according to geographical location, particularly provision of initial information and ongoing VI support.Conclusions: This study highlights a significant variation in the support and information received by people in the UK with nystagmus. It also supports the role of charities and increasingly, social media in the provision of patient information. The study also highlights the need for standardized guidelines for the management of patients with nystagmus, particularly with regard to support and information.

Quantifying normal and parkinsonian gait features from home movies: Practical application of a deep learning-based 2D pose estimator.

Gait movies recorded in daily clinical practice are usually not filmed with specific devices, which prevents neurologists benefitting from leveraging gait analysis technologies. Here we propose a novel unsupervised approach to quantifying gait features and to extract cadence from normal and parkinsonian gait movies recorded with a home video camera by applying OpenPose, a deep learning-based 2D-pose estimator that can obtain joint coordinates from pictures or videos recorded with a monocular camera. Our proposed method consisted of two distinct phases: obtaining sequential gait features from movies by extracting body joint coordinates with OpenPose; and estimating cadence of periodic gait steps from the sequential gait features using the short-time pitch detection approach. The cadence estimation of gait in its coronal plane (frontally viewed gait) as is frequently filmed in the daily clinical setting was successfully conducted in normal gait movies using the short-time autocorrelation function (ST-ACF). In cases of parkinsonian gait with prominent freezing of gait and involuntary oscillations, using ACF-based statistical distance metrics, we quantified the periodicity of each gait sequence; this metric clearly corresponded with the subjects' baseline disease statuses. The proposed method allows us to analyze gait movies that have been underutilized to date in a completely data-driven manner, and might broaden the range of movies for which gait analyses can be conducted.

Adaptive notch filter for pathological tremor suppression using permanent magnet linear motor

Tremor is a progressive neurological disease involving involuntary rhythmic muscle movements and oscillations of the human body parts by alternating contractions of muscles. Tremor is a common symptom that can severely limit the independence of affected individuals and their ability to perform activities of daily living. In this paper, a permanent magnet linear motor (PMLM) and a notch filter with an adaptive frequency estimator are employed to suppress pathological tremor. The effects of undesired intrinsic forces exhibited by the use of PMLM were minimized by development and parameter identification of a dynamic force model. The experimental evaluation of a real-time adaptive tremor identification and suppression controller was performed in a human joints emulator using recorded signals from participants with Parkinson’s disease and essential tremor. We employed wavelet transform to analyze the tremor signals and the performance of the controller in the time-frequency domain. Experimental results showed an average tremor suppression of 30.51 dB (97.0%) and 13.89 dB (79.8%) in the first and second tremor frequency components, respectively. The average resistance induced by the orthotic mechanism against the voluntary motion was 0.36 N, and a 7.74 dB reduction with an active force compensator was observed. Compared to a servo-pneumatic actuator, a PMLM offers higher energy efficiency at a comparable suppression performance.

Next-generation sequencing identifies a novel frameshift variant in FRMD7 in a Chinese family with idiopathic infantile nystagmus.

BackgroundIdiopathic infantile nystagmus (IIN) is a high genetically heterogeneous ophthalmic disease and is often associated with pathogenic mutations in FRMD7 and GPR143, respectively. Idiopathic infantile nystagmus manifests as involuntary periodic rhythmic oscillation of the eyes in the very early life, which decreases visual acuity and affects the quality of life.Objective and MethodsThe aim of our study was to reveal a possible pathogenic variant through the investigation of a Chinese Han family with IIN with an implementation of a next‐generation sequencing method. Isolated DNA analysis was followed by Sanger sequencing validation. We also performed the detailed ophthalmological examination of family members.ResultsWe identified a novel frameshift variant in FRMD7 (NM_194277.2: c.1419_1422dup, p.Tyr475fs), which leads to a frameshift mutation since tyrosine (Tyr) at 475 codon of FRMD7 protein (p.Tyr475fs) and co‐segregates with IIN phenotype in this family.ConclusionsWe found a novel frameshift FRMD7 variant in a Chinese Han family, which may be causative variant for IIN and can further enrich the mutation spectrum and uncover the etiology of IIN.

Facio-Oculo-Palatal Myoclonus Complicated by a Recurrent Brainstem Stroke

<strong>Background:</strong> A 54-year-old Thai male who has suffered from multiple episodes of ischemic and hemorrhagic strokes developed facio-oculo-palatal myoclonus (FOPM) 1 month after the latest episode of the brainstem stroke. <strong>Phenomenology Shown:</strong> The patient presented with semirhythmic, involuntary, horizontal jerky, and rotatory ocular oscillation concomitant with asymmetrical palatal and perioral myoclonus consistent with FOPM. <strong>Educational value:</strong> FOPM is a useful clinical clue for diagnosing brainstem lesions, specifically in the Guillain–Mollaret triangle. The commonest etiology is cerebrovascular diseases.

Comparison of automated Hematopoietic Progenitor Cell (HPC) count between Sysmex XN and the CD34+ ISHAGE in apheresis samples

Tremor is a progressive neurological disease involving involuntary rhythmic muscle movements and oscillations of the human body parts by alternating contractions of muscles. Tremor is a common symptom that can severely limit the independence of affected individuals and their ability to perform activities of daily living. In this paper, a permanent magnet linear motor (PMLM) and a notch filter with an adaptive frequency estimator are employed to suppress pathological tremor. The effects of undesired intrinsic forces exhibited by the use of PMLM were minimized by development and parameter identification of a dynamic force model. The experimental evaluation of a real-time adaptive tremor identification and suppression controller was performed in a human joints emulator using recorded signals from participants with Parkinson’s disease and essential tremor. We employed wavelet transform to analyze the tremor signals and the performance of the controller in the time-frequency domain. Experimental results showed an average tremor suppression of 30.51 dB (97.0%) and 13.89 dB (79.8%) in the first and second tremor frequency components, respectively. The average resistance induced by the orthotic mechanism against the voluntary motion was 0.36 N, and a 7.74 dB reduction with an active force compensator was observed. Compared to a servo-pneumatic actuator, a PMLM offers higher energy efficiency at a comparable suppression performance.

Studies on a Robotic Device that Minimizes End-Point Vibrations for Parkinson Tremor

Parkinson tremor is a neuromotor condition that produces involuntary oscillation movements in some parts of the body, especially at the upper limbs. This disease affects more than 10 million people in the world and around 150 thousand people in Turkey, according to the report by the World Health Organization. This work focuses on simulating a robotic device in the shape of a glass for drinking liquids, which is an ordinary action for a normal person but can be very difficult for a Parkinson patient. This robotic device can minimize end-point vibrations when it is manipulated by people suffering from tremor. The work makes use of real-time data gathered from a patient, presents studies to characterize the main frequency of the tremor, and employs this information for designing an active control method. The proposed control method is based on the inverse dynamics of the vibrating system to damp the tremor’s first vibrational frequency component. The work consists of three stages: data acquisition, characterization and simulation of the control action. The first stage involves acceleration sensors based movement analysis to identify the frequencies and the behavior of the tremor; followed by a signal processing approach is developed using the fast Fourier transform. The studies indicate that the tremor could be represented by a harmonic signal in which the first frequency mode is the most representative. This assumption allows for simplifying our control strategy: inverse dynamics in an open-loop control along with proportional-derivative closed-loop controller are performed. The experimental data acquisition, signal analysis and control simulations were realized via Matlab/Simulink. The results illustrate the system performance validating our assumptions and the success of the control method we propose, which could lead to the design of a device to minimize vibrations at the end-point of the glass.

Tremor in motor neuron disease may be central rather than peripheral in origin.

Motor neuron disease (MND) refers to a spectrum of degenerative diseases affecting motor neurons. Recent clinical and post-mortem observations have revealed considerable variability in the phenotype. Rhythmic involuntary oscillations of the hands during action, resembling tremor, can occur in MND, but their pathophysiology has not yet been investigated. A total of 120 consecutive patients with MND were screened for tremor. Twelve patients with action tremor and no other movement disorders were found. Ten took part in the study. Tremor was recorded bilaterally using surface electromyography (EMG) and triaxial accelerometer, with and without a variable weight load. Power spectra of rectified EMG and accelerometric signal were calculated. To investigate a possible cerebellar involvement, eyeblink classic conditioning was performed in five patients. Action tremor was present in about 10% of our population. All patients showed distal postural tremor of low amplitude and constant frequency, bilateral with a small degree of asymmetry. Two also showed simple kinetic tremor. A peak at the EMG and accelerometric recordings ranging from 4 to 12 Hz was found in all patients. Loading did not change peak frequency in either the electromyographic or accelerometric power spectra. Compared with healthy volunteers, patients had a smaller number of conditioned responses during eyeblink classic conditioning. Our data suggest that patients with MND can present with action tremor of a central origin, possibly due to a cerebellar dysfunction. This evidence supports the novel idea of MND as a multisystem neurodegenerative disease and that action tremor can be part of this condition.

Visual Target Strategies in Infantile Nystagmus Patients With Horizontal Jerk Waveform.

The aim of this study was to propose a new pathophysiological hypothesis for involuntary eye oscillation in infantile nystagmus (IN): patients with IN exhibit impaired gaze fixation, horizontal smooth pursuit and optokinetic nystagmus (OKN) and use saccadic eye movements for these underlying impairments. In order to induce saccades, they make enough angle between gaze and target by precedent exponential slow eye movements. IN consists of the alternate appearance of the saccade and the slow eye movements. Unlike most previous theories, IN is therefore considered a necessary strategy allowing for better vision and not an obstacle to clear vision. In five patients with IN, eye movements were analyzed during the smooth pursuit test, saccadic eye movement test, OKN test and vestibulo-ocular reflex (VOR) test. Their gaze fixation, horizontal smooth pursuit, OKN and the last half of the slow phase of VOR were impaired. The lines obtained by connection of the end eye positions of fast phase of nystagmus coincided with the trajectories of targets. The findings indicate that patients followed the target by the fast but not the slow phase of nystagmus, which supports our hypothesis. By setting the direction of slow phase of nystagmus opposite to the direction of the OKN stimulation, enough angle can be effectively made between the gaze and target for the induction of saccade. This is the mechanism of reversed OKN response. In darkness and when eyes are closed, IN weakens because there is no visual target and neither the saccade for catching up the target or slow phase for induction of the saccade is needed.