A Sparse Matrix Approach for Simultaneous Quantification of Nystagmus and Saccade

The vestibulo-ocular reflex (VOR) consists of two intermingled non-linear subsystems; namely, nystagmus and saccade. Typically, nystagmus is analysed using a single sufficiently long signal or a concatenation of them. Saccade information is not analysed and discarded due to insufficient data length to provide consistent and minimum variance estimates. This paper presents a novel sparse matrix approach to system identification of the VOR. It allows for the simultaneous estimation of both nystagmus and saccade signals. We show via simulation of the VOR that our technique provides consistent and unbiased estimates in the presence of output additive noise

An Indirect System Identification Technique for Stable Estimation of Continuous-Time Parameters of the Vestibulo-Ocular Reflex (VOR)

The vestibulo-ocular reflex (VOR) is a well-known dual mode bifurcating system that consists of slow and fast modes associated with nystagmus and saccade, respectively. Estimation of continuous-time parameters of nystagmus and saccade models are known to be sensitive to estimation methodology, noise and sampling rate. The stable and accurate estimation of these parameters are critical for accurate disease modelling, clinical diagnosis, robotic control strategies, mission planning for space exploration and pilot safety, etc. This paper presents a novel indirect system identification method for the estimation of continuous-time parameters of VOR employing standardised least-squares with dual sampling rates in a sparse structure. This approach permits the stable and simultaneous estimation of both nystagmus and saccade data. The efficacy of this approach is demonstrated via simulation of a continuous-time model of VOR with typical parameters found in clinical studies and in the presence of output additive noise

The role of non-invasive camera technology for gait analysis in patients with vestibular disorders

Purpose of the study Current balance assessments performed in clinical settings do not provide objective measurements of gait. Further, objective gait analysis typically requires expensive, large and dedicated laboratory facilities. The aim of this pilot study was to develop and assess a low-cost, non-invasive camera technology for gait analysis, to assist the clinical assessment of patients with vestibular disorders. Materials and methods used This is a prospective, case-controlled study that was developed jointly by the local Neurotology Department and the Centre for Sports Engineering Research. Eligible participants were approached and recruited at the local Neurotology Clinic. The gait assessment included two repetitions of a straight 7-metre walk. The gait analysis system, comprised of a camera (P3215-V, Axis Communications, Sweden) and analysis software was installed in an appropriately sized clinic room. Parameters extruded were walking velocity, step velocity, step length, cadence and step count per meter. The effect sizes (ESB) were calculated using the MatLab and were considered large, medium or small if >0.8, 0.5 and 0.2 respectively. This study was granted ethical approval by the Coventry and Warwickshire Research Ethics Committee (15/WM/0448). Results Six patients with vestibular dysfunction (P group) and six age-matched healthy volunteers (V group) were recruited in this study. The average velocity of gait for P group was 1189.1 ± 69.0 mm·s-1 whereas for V group it was 1351.4 ± 179.2 mm·s-1, (ESB: -0.91). The mean step velocities were 1353.1 ± 591.8 mm·s-1 and 1434.0 ± 396.5 mm·s-1 for P and V groups respectively (ESB: -0.20). The average cadence was 2.3 ± 0.9 Hz and 2.0 ± 0.5 Hz for P and V groups respectively (ESB: 0.60). The mean step length was 620.5 ± 150.7 mm for the P group and 728.5 ± 86.0 mm for the V group (ESB = -1.26). The average step count per meter was 1.7 ± 0.3 and 1.4 ± 0.1 for P and V groups respectively (ESB = 3.38). Conclusion This pilot study used a low-cost, non-invasive camera technology to identify changes in gait characteristics. Further, gait measurements were obtained without the application of markers or sensors to patients (i.e. non-invasive), thus allowing current, clinical practice to be supplemented by objective measurement, with minimal procedural impact. Further work needs to be undertaken to refine the device and produce normative data. In the future, similar technologies could be used in the community setting, providing an excellent diagnostic and monitoring tool for balance patients

Functional Magnetic Resonance Imaging

"Functional Magnetic Resonance Imaging - Advanced Neuroimaging Applications" is a concise book on applied methods of fMRI used in assessment of cognitive functions in brain and neuropsychological evaluation using motor-sensory activities, language, orthographic disabilities in children. The book will serve the purpose of applied neuropsychological evaluation methods in neuropsychological research projects, as well as relatively experienced psychologists and neuroscientists. Chapters are arranged in the order of basic concepts of fMRI and physiological basis of fMRI after event-related stimulus in first two chapters followed by new concepts of fMRI applied in constraint-induced movement therapy; reliability analysis; refractory SMA epilepsy; consciousness states; rule-guided behavioral analysis; orthographic frequency neighbor analysis for phonological activation; and quantitative multimodal spectroscopic fMRI to evaluate different neuropsychological states

Change blindness: eradication of gestalt strategies

Arrays of eight, texture-defined rectangles were used as stimuli in a one-shot change blindness (CB) task where there was a 50% chance that one rectangle would change orientation between two successive presentations separated by an interval. CB was eliminated by cueing the target rectangle in the first stimulus, reduced by cueing in the interval and unaffected by cueing in the second presentation. This supports the idea that a representation was formed that persisted through the interval before being 'overwritten' by the second presentation (Landman et al, 2003 Vision Research 43149–164]. Another possibility is that participants used some kind of grouping or Gestalt strategy. To test this we changed the spatial position of the rectangles in the second presentation by shifting them along imaginary spokes (by ±1 degree) emanating from the central fixation point. There was no significant difference seen in performance between this and the standard task [F(1,4)=2.565, p=0.185]. This may suggest two things: (i) Gestalt grouping is not used as a strategy in these tasks, and (ii) it gives further weight to the argument that objects may be stored and retrieved from a pre-attentional store during this task

Genetic dissection of circuits underlying the modular structure of the Superior Colliculus

In order to successfully interact with the environment, animals need to produce accurate movements towards specific positions in space. A crucial region of the brain that guides such goal-oriented movements is the superior colliculus (SC), an evolutionary conserved structure of the midbrain. While several lines of research in different model organisms have confirmed that the SC contributes to the initiation of orienting movements, how functionally distinct neuronal groups within the SC are organized to support the production of such motor outputs is poorly understood. One of the reasons why the intrinsic circuit organization of the SC remains elusive is the lack of genetic characterization of the neuronal populations of the motor SC. Here, we performed RNAseq to screen for genetic markers for neuronal subpopulations in the motor SC. We identified a transcription factor, Pitx2, which is exclusively expressed in a subpopulation of glutamatergic neurons in the motor domain of the SC. Strikingly, this population of neurons displays a non-homogenous distribution within the motor layer of the SC, being organised in clusters along the mediolateral and anteroposterior axis. We mapped the pre-synaptic network and the post-synaptic targets of Pitx2ON neurons, unveiling that this modular population receives direct inputs from motor and sensory cortical regions, as well as several midbrain nuclei involved in movement control, and sends projection along the cephalomotor pathway. We then asked whether these modules may act as functional units, each integrating multimodal sensory information and encoding a specific feature of head movement, the main ethologically relevant orienting behaviour in rodents. Optogenetic activation of this modular population in freely moving animals produced a stereotyped, robust head motion characterised by a pronounced quantal nature; furthermore, the amplitude of the elicited head movement varied based on the modular unit activated. Our results suggest that distinct clusters of genetically defined neurons produce head displacement along a characteristic vector. In conclusion, we found that a population of premotor neurons in the SC is organised in a modular conformation and we suggest that such modularity may represent a physical implementation of a discontinuous motor map for orienting movements encoded in the mouse SC. Our work complements previous observations of periodicity in SC circuitry, as well as its afferent and efferent systems. Exploiting the genetic toolkit available in the mouse, our work begins to address the functional relevance of this modularity and paves the way for future experiments to investigate principles of sensorimotor integration in SC circuits.MR

A molecular-genetic study of Congenital Nystagmus

Nystagmus is a disorder of eye movement characterised by irregular, uncontrolled and repetitive eye movements. It can occur in a broad spectrum of clinical situations and diseases or it may occur in isolation and an inherited disorder. Surprisingly little is known about the underlying mechanisms of ocular-motor control. Similarly, the pathophysiological mechanisms underpinning nystagmus is also poorly understood. By studying pedigrees in whom nystagmus seems to be inherited as an isolated trait (Congenital Idiopathic Nystagmus), it may be possible to identify some of the genetic causes of this disorder and subsequently understand the pathophysiology.This thesis describes a molecular genetic study of congenital nystagmus. A clinical phenotyping study is followed by linkage analysis and positional cloning. A novel nystagmus gene is investigated in a large cohort of Congenital Idiopathic Nystagmus (CIN) patients and X-inactivation studies are performed. Subsequently, cell culture and RT-PCR work is performed to study expression of this gene. Additionally a pedigree with an atypical congenital nystagmus disorder is investigated and a new mutation within a known cerebellar disease gene is identified.This work contributed to the identification of the first gene for Congenital Idiopathic Nystagmus (CIN). The first detailed temporal expression study of the FRMD7 nystagmus gene was also performed in this study which has directed further studies into the pathogenesis of CIN. Identification of a new mutation in the CACNA1A gene in a pedigree with nystagmus and subtle cerebellar signs has lead to the consideration of this gene in patients who present to hospital with isolated atypical nystagmus

Sensory mechanisms of balance control in cerebellar disease

A wealth of evidence exists to suggest that the cerebellum has an important role in the integration of vestibular, proprioceptive and visual sensory signals. Human bipedal balance depends on sensory integration and balance impairment is a common feature of cerebellar disease. I test the hypothesis that disrupted sensori-motor processing is responsible for balance impairment in cerebellar disease. Balance control in subjects with pure cerebellar disease (SCA6) was compared with matched healthy subjects using a mix of traditional clinical and laboratory-based tests. Sensory processing was explored using a novel combination of tools designed to deliver single-sensory channel balance perturbations. The vestibular, proprioceptive and visual channels were stimulated with galvanic vestibular stimulation, vibration and visual scene motion respectively. Standing balance was explored using 3D whole body motion analysis. Sway speed when standing quietly with eyes open was significantly increased in those with SCA6 and strongly correlated with disease severity scores. Responses to isolated vestibular stimulation suggest largely normal vestibulo-motor processing in SCA6 subjects. Responses had normal latency and magnitude. Response direction followed head position in the normal way suggesting intact vestibulo-proprioceptive integration. Vision had a normal attenuating effect on response magnitude suggesting intact vestibulo-visual integration. Responses to isolated vestibular, proprioceptive and visual stimuli responses were compared to investigate whether there might be a predominant deficit in any one channel. Vestibular and proprioceptive stimuli evoked largely normal responses. In contrast, visual stimuli consistently evoked abnormally large responses with significant timing delays. Increases in SCA6 response magnitudes to moving visual stimuli strongly correlated with disease severity scores. This finding is the first to point to a specific change in sensori-motor processing in cerebellar disease. This finding could contribute to balance impairments but is unlikely to explain balance impairment observed with the eyes closed. Overall sensory processing for balance control in SCA6 is largely intact