Amir Kheradmand

Cerebellum and Ocular Motor Control

An intact cerebellum is a prerequisite for optimal ocular motor performance. The cerebellum fine-tunes each of the subtypes of eye movements so they work together to bring and maintain images of objects of interest on the fovea. Here we review the major aspects of the contribution of the cerebellum to ocular motor control. The approach will be based on structural–functional correlation, combining the effects of lesions and the results from physiologic studies, with the emphasis on the cerebellar regions known to be most closely related to ocular motor function: (1) the flocculus/paraflocculus for high-frequency (brief) vestibular responses, sustained pursuit eye movements, and gaze holding, (2) the nodulus/ventral uvula for low-frequency (sustained) vestibular responses, and (3) the dorsal oculomotor vermis and its target in the posterior portion of the fastigial nucleus (the fastigial oculomotor region) for saccades and pursuit initiation.

Transcranial Magnetic Stimulation (TMS) of the Supramarginal Gyrus: A Window to Perception of Upright

Although the pull of gravity, primarily detected by the labyrinth, is the fundamental input for our sense of upright, vision and proprioception must also be integrated with vestibular information into a coherent perception of spatial orientation. Here, we used transcranial magnetic stimulation (TMS) to probe the role of the cortex at the temporal parietal junction (TPJ) of the right cerebral hemisphere in the perception of upright. We measured the perceived vertical orientation of a visual line; that is, the subjective visual vertical (SVV), after a short period of continuous theta burst stimulation (cTBS) with the head upright. cTBS over the posterior aspect of the supramarginal gyrus (SMGp) in 8 right-handed subjects consistently tilted the perception of upright when tested with the head tilted 20° to either shoulder (right: 3.6°, left: 2.7°). The tilt of SVV was always in the direction opposite to the head tilt. On the other hand, there was no significant tilt after sham stimulation or after cTBS of nearby areas. These findings suggest that a small area of cerebral cortex--SMGp--has a role in processing information from different sensory modalities into an accurate perception of upright.

Repositioning Maneuvers for Benign Paroxysmal Positional Vertigo

Opinion statementThere are few conditions in neurology that are diagnosed with such ease and certainty as benign paroxysmal positional vertigo (BPPV). Repositioning maneuvers are highly effective in treating BPPV, inexpensive, and easy to apply. Surgery has a very minor role in the management of BPPV, and although medications may transiently ameliorate symptoms, they do not treat the underlying process. There is good evidence to support treatment of posterior canal BPPV with Epley or Semont maneuvers and horizontal canal BPPV with Gufoni maneuvers or BBQ roll (also known as Lempert 360 roll or log roll); and weaker evidence for head hanging maneuvers in the least common anterior canal variant. Since the therapeutic efficacy amongst maneuvers for each canal is comparable, the choice of treatment is generally based on clinician preference, complexity of the maneuvers themselves, poor treatment response to specific maneuvers, and musculoskeletal considerations such as arthritic changes and range of motion of the cervical spine.Treating posterior canal BPPV with Epley or Semont manuevers is comparable as far as efficacy and the ease with which maneuvers are performed.For horizontal canal BPPV, the Gufoni maneuver is easier to perform compared to the BBQ roll, as it requires that the clinician only identify the side of weaker nystagmus (regardless of whether it’s geotropic or apogeotropic) and not necessarily the side involved.Anterior canal BPPV is rare and generally short-lived, but there is weak evidence that deep head hanging and a variety of eponymous maneuvers may hasten recovery. The advantage of deep head hanging maneuvers is that they can be effectively performed without knowledge of the side involved.

Temporal constancy of perceived direction of gravity assessed by visual line adjustments

Here we investigated how well internal estimates of direction of gravity are preserved over time and if the subjective visual vertical (SVV) and horizontal (SVH) can be used inter-changeably. Fourteen human subjects repetitively aligned a luminous line to SVV, SVH or subjective visual oblique (± 45°) over 5 min in otherwise complete darkness and also in dim light. Both accuracy (i.e., the degree of veracity as reflected by the median adjustment error) and precision (i.e., the degree of reproducability as reflected by the trial-to-trial variability) of adjustments along the principle axes were significantly higher than along the oblique axes. Orthogonality was only preserved in a minority of subjects. Adjustments were significantly different between SVV vs. SVH (7/14 subjects) and between ±45° vs. -45° (12/14) in darkness and in 6/14 and 14/14 subjects, respectively, in dim light. In darkness, significant drifts over 5min were observed in a majority of trials (33/56). Both accuracy and precision were higher if more time was taken to make the adjustment. These results introduce important caveats when interpreting studies related to graviception. The test re-test reliability of SVV and SVH can be influenced by drift of the internal estimate of gravity. Based on spectral density analysis we found a noise pattern consistent with 1/fβ noise, indicating that at least part of the trial-to-trial dynamics observed in our experiments is due to the dependence of the serial adjustments over time. Furthermore, using results from the SVV and SVH inter-changeably may be misleading as many subjects do not show orthogonality. The poor fidelity of perceived ± 45° indicates that the brain has limited ability to estimate oblique angles.

Knowing what the brain is seeing in three dimensions: A novel, noninvasive, sensitive, accurate, and low-noise technique for measuring ocular torsion

Torsional eye movements are rotations of the eye around the line of sight. Measuring torsion is essential to understanding how the brain controls eye position and how it creates a veridical perception of object orientation in three dimensions. Torsion is also important for diagnosis of many vestibular, neurological, and ophthalmological disorders. Currently, there are multiple devices and methods that produce reliable measurements of horizontal and vertical eye movements. Measuring torsion, however, noninvasively and reliably has been a longstanding challenge, with previous methods lacking real-time capabilities or suffering from intrusive artifacts. We propose a novel method for measuring eye movements in three dimensions using modern computer vision software (OpenCV) and concepts of iris recognition. To measure torsion, we use template matching of the entire iris and automatically account for occlusion of the iris and pupil by the eyelids. The current setup operates binocularly at 100 Hz with noise <0.1° and is accurate within 20° of gaze to the left, to the right, and up and 10° of gaze down. This new method can be widely applicable and fill a gap in many scientific and clinical disciplines.

Ischemic Stroke in Evolution: Predictive Value of Perfusion Computed Tomography

BACKGROUND Various perfusion computed tomography (PCT) parameters have been used to identify tissue at risk of infarction in the setting of acute stroke. The purpose of this study was to examine predictive value of the PCT parameters commonly used in clinical practice to define ischemic penumbra. The patient selection criterion aimed to exclude the effect of thrombolysis from the imaging data. METHODS Consecutive acute stroke patients were screened and a total of 18 patients who initially underwent PCT and CT angiogram (CTA) on presentation but did not qualify to receive thrombolytic therapy were selected. The PCT images were postprocessed using a delay-sensitive deconvolution algorithm. All the patients had follow-up noncontrast CT or magnetic resonance imaging to delineate the extent of their infarction. The extent of lesions on PCT maps calculated from mean transit time (MTT), time to peak (TTP), cerebral blood flow, and cerebral blood volume were compared and correlated with the final infarct size. A collateral grading score was used to measure collateral blood supply on the CTA studies. RESULTS The average size of MTT lesions was larger than infarct lesions (P < .05). The correlation coefficient of TTP/infarct lesions (r = .95) was better than MTT/infarct lesions (r = .66) (P = .004). CONCLUSIONS A widely accepted threshold to define MTT lesions overestimates the ischemic penumbra. In this setting, TTP with appropriate threshold is a better predictor of infarct in acute stroke patients. The MTT/TTP mismatch correlates with the status of collateral blood supply to the tissue at risk of infarction.

Damping of monocular pendular nystagmus with vibration in a patient with multiple sclerosis

Acquired pendular nystagmus (PN) occurs commonly in multiple sclerosis (MS) and results in a highly disabling oscillopsia that impairs vision. It usually consists of pseudo-sinusoidal oscillations at a single frequency (3–5 Hz) that often briefly stop for a few hundred milliseconds after saccades and blinks. The oscillations are thought to arise from instability in the gaze-holding networks (“neural integrator”) in the brainstem and cerebellum.1,2 Here we describe a patient with monocular PN in whom vibration on the skull from a handheld muscle massager strikingly diminished or stopped her nystagmus.

Eye movements in vestibular disorders

The differential diagnosis of patients with vestibular symptoms usually begins with the question: is the lesion central or is it peripheral? The answer commonly emerges from a careful examination of eye movements, especially when the lesion is located in otherwise clinically silent areas of the brain such as the vestibular portions of the cerebellum (flocculus, paraflocculus which is called the tonsils in humans, nodulus, and uvula) and the vestibular nuclei as well as immediately adjacent areas (the perihypoglossal nuclei and the paramedian nuclei and tracts). The neural circuitry that controls vestibular eye movements is intertwined with a larger network within the brainstem and cerebellum that also controls other types of conjugate eye movements. These include saccades and pursuit as well as the mechanisms that enable steady fixation, both straight ahead and in eccentric gaze positions. Navigating through this complex network requires a thorough knowledge about all classes of eye movements to help localize lesions causing a vestibular disorder. Here we review the different classes of eye movements and how to examine them, and then describe common ocular motor findings associated with central vestibular lesions from both a topographic and functional perspective.

The bedside examination of the vestibulo-ocular reflex (VOR): An update

Diagnosing dizzy patients remains a daunting challenge to the clinician in spite of modern imaging and increasingly sophisticated electrophysiological testing. Here we review the major bedside tests of the vestibulo-ocular reflex and how, when combined with a proper examination of the other eye movement systems, one can arrive at an accurate vestibular diagnosis.

Perception of upright: Multisensory convergence and the role of temporo-parietal cortex

We inherently maintain a stable perception of the world despite frequent changes in the head, eye, and body positions. Such “orientation constancy” is a prerequisite for coherent spatial perception and sensorimotor planning. As a multimodal sensory reference, perception of upright represents neural processes that subserve orientation constancy through integration of sensory information encoding the eye, head, and body positions. Although perception of upright is distinct from perception of body orientation, they share similar neural substrates within the cerebral cortical networks involved in perception of spatial orientation. These cortical networks, mainly within the temporo-parietal junction, are crucial for multisensory processing and integration that generate sensory reference frames for coherent perception of self-position and extrapersonal space transformations. In this review, we focus on these neural mechanisms and discuss (i) neurobehavioral aspects of orientation constancy, (ii) sensory models that address the neurophysiology underlying perception of upright, and (iii) the current evidence for the role of cerebral cortex in perception of upright and orientation constancy, including findings from the neurological disorders that affect cortical function.