Arun N. Kumar

Effects of eyelid closure, blinks, and eye movements on the electroencephalogram

OBJECTIVEnTo characterize the effects of the eyeball and eyelid positions during eyeblinks on electroencephalographic (EEG) potentials.nnnMETHODSnMovements of the upper eyelids and eyes were measured in two healthy subjects using the magnetic search coil technique during horizontal and vertical eye rotations, eyeblinks, and lid closure. Corresponding signal changes were recorded simultaneously on the electroencephalogram (EEG).nnnRESULTSnSpontaneous blinks produced small eye movements directed down and inward, whereas slow or forced blinks were associated with delayed upward eye rotations (i.e. Bells phenomenon); both types of blinks caused positive EEG potentials with bifrontal distribution maximum at Fp1 and Fp2.nnnCONCLUSIONSnIn prior reports, these positive EEG artifacts have been attributed to upward eyeball rotation during blinks-Bells phenomenon. By contrast, our findings indicate that movements of the eyelid contribute to a greater extent to these EEG potentials than do upward eyeball rotations.nnnSIGNIFICANCEnCare is required in attributing EEG artifacts to movements of either eyeball or eyelid, since our findings suggest that they both contribute to these potentials.

Molecular characterization and delineation of subtle deletions in de novo "balanced" chromosomal rearrangements

Abstract To test the hypothesis that the phenotypic abnormalities seen in cases with apparently balanced chromosomal rearrangements are the result of the presence of cryptic deletions or duplications of chromosomal material near the breakpoints, we analyzed three cases with apparently balanced chromosomal rearrangements and phenotypic abnormalities. We characterized the breakpoints in these cases by using microsatellite analysis by polymerase chain reaction and fluorescence in situ hybridization analysis of yeast artificial chromosome clones selected from the breakpoint regions. Molecular characterization of the translocation breakpoint in patient 1 [46,XY,t(2;6)(p22.2;q23.1)] showed the presence of a 4- to 6-Mb cryptic deletion between markers D6S412 and D6S1705 near the 6q23.1 breakpoint. Molecular characterization of the proximal inversion 7q22.1 breakpoint in patient 2 [46,XY,inv(7)(q22.1q32.1)] revealed the presence of a 4-Mb cryptic deletion between D7S651 and D7S515 markers. No deletion or duplication of chromosomal material was found near the breakpoints in patient 3 [46,XX,t(2;6)(q33.1;p12.2)]. Our study suggests that a systematic molecular study of breakpoints should be carried out in cases with apparently balanced chromosomal rearrangements and phenotypic abnormalities, because cryptic deletions near the breakpoints may explain the phenotypic abnormalities in these cases.

Abnormalities of optokinetic nystagmus in progressive supranuclear palsy

Objectives: To measure vertical and horizontal responses to optokinetic (OK) stimulation and investigate directional abnormalities of quick phases in progressive supranuclear palsy (PSP). Methods: Saccades and OK nystagmus were studied in six PSP patients, five with Parkinson’s disease (PD), and 10 controls. The OK stimulus subtended 72° horizontally, 60° vertically, consisted of black and white stripes, and moved at 10–50°/s. Results: All PSP patients showed slowed voluntary vertical saccades and nystagmus quick phases compared with PD or controls. Small, paired, horizontal saccadic intrusions (SWJ) were more frequent and larger in PSP during fixation. Vertical saccades were transiently faster at the time of SWJ and horizontal saccades in PSP. During vertical OK nystagmus, small quick phases were often combined with horizontal SWJ in all subjects; in PSP the vector was closer to horizontal. Vertical OK slow phase gain was reduced in PSP but, in most PD patients, was similar to normals. The average position of gaze shifted in the direction of vertical OK stimulus in PSP patients with preserved slow phase responses but impaired quick phases. Conclusions: Vertical OK responses in PSP show impaired slow phase responses, and quick phases that are slowed and combined with SWJ to produce an oblique vector. SWJ facilitate vertical saccades and quick phases in PSP, but it is unclear whether this is an adaptive process or a result of the disease. A large OK stimulus is useful to induce responses that can be quantitatively analysed in patients with limited voluntary range of vertical gaze.

Evaluating small eye movements in patients with saccadic palsies.

Slow saccades are an important diagnostic feature of a range of degenerative, metabolic, and genetic diseases of the nervous system. Many affected patients have difficulty initiating saccades, and the movements themselves may be small, making it difficult to make comparisons with control subjects. A large‐field optokinetic stimulus may elicit quick phases of nystagmus in patients who cannot initiate voluntary saccades, but these movements may also be small. We show that it is still possible to compare amplitude‐duration and amplitude‐peak velocity relations with controls if data are fit with a power function (rather than an exponential equation). When analyzed this way, the dynamic properties of small saccades and quick phases from patients with progressive supranuclear palsy (PSP) could be differentiated from fast movements made by patients with idiopathic Parkinsons disease or controls. Normal saccades show a fairly constant ratio: peak velocity/mean velocity (Q ∼1.6 for vertical saccades). This ratio was abnormally high (Q >3) for some larger saccades made by patients with PSP, suggesting that either these movements were not entirely saccadic or that they were composed of a series of small saccades.

Tests of Models for Saccade–Vergence Interaction using Novel Stimulus Conditions

During natural activities, two types of eye movements – saccades and vergence – are used in concert to point the fovea of each eye at features of interest. Some electrophysiological studies support the concept of independent neurobiological substrates for saccades and vergence, namely saccadic and vergence burst neurons. Discerning the interaction of these two components is complicated by the near-synchronous occurrence of saccadic and vergence components. However, by positioning the far target below the near target, it is possible to induce responses in which the peak velocity of the vertical saccadic component precedes the peak velocity of the horizontal vergence component by ∼ 75xa0ms. When saccade–vergence responses are temporally dissociated in this way, the vergence velocity waveform changes, becoming less skewed. We excluded the possibility that such change in skewing was due to visual feedback by showing that similar behavior occurred in darkness. We then tested a saccade-related vergence burst neuron (SVBN) model proposed by Zee etxa0al. in J Neurophysiol 68:1624–1641 (1992), in which omnipause neurons remove inhibition from both saccadic and vergence burst neurons. The technique of parameter estimation was used to calculate optimal values for responses from human subjects in which saccadic and convergence components of response were either nearly synchronized or temporally dissociated. Although the SVBN model could account for convergence waveforms when saccadic and vergence components were nearly synchronized, it could not when the components were temporally dissociated. We modified the model so that the saccadic pulse changed the parameter values of the convergence burst units if both components were synchronized. The modified model accounted for velocity waveforms of both synchronous and dissociated convergence movements. We conclude that both the saccadic pulse and omnipause neuron inhibition influence the generation of vergence movements~when they are made synchronously with saccades.

Molecular Cytogenetics of a De Novo Interstitial Deletion of Chromosome Arm 6q in a Developmentally Normal Girl

Using fluorescence in situ hybridization and microsatellite analysis, we have characterized a de novo interstitial deletion on the long arm of chromosome 6 [46,XX,del(6) (q23.3q24.2)] in a developmentally normal girl with very mild phenotypic abnormalities. The deletion was paternal in origin and was between markers WI-5023 and D6S1042. The size of the deletion was estimated to be approximately 4-5 Mb. The normal phenotype in this patient might be the result of imprinting of paternal copies of genes located in the segment 6q23. 3-q24.2. Alternatively, the genes located in the segment 6q23.3-q24. 2 might not be subject to dosage effects and therefore the haploinsufficiency of genes in this segment might not have phenotypic consequences.

Evaluating Large Saccades in Patients with Brain‐Stem or Cerebellar Disorders

Abstract: Clinicians conventionally test saccades at the bedside by noting the accuracy, initiation time, and speed of large movements, with the patients head stationary. Partly for methodological reasons, laboratory analysis of saccades has mainly focused on movements of 20 degrees or less. By measuring the velocity waveform of large saccades, it is possible to examine more closely the way in which brain stem and cerebellum guide the eye to the target. Large saccades made by healthy humans show a positively skewed velocity profile. Slow saccades made by patients with brain‐stem disorders show a prolonged plateau of low velocity. Some patients with cerebellar disorders may show increased acceleration and deceleration of saccades. Each of these velocity waveforms can be modeled by changing the parameters that describe medium‐lead burst neuron firing. In certain other brain‐stem and cerebellar disorders, transient decelerations or premature terminations of saccades occur; such velocity waveforms cannot be modeled solely by changing the parameters that describe burst neuron firing. Instead, it is necessary to postulate dysfunction of the mechanism that normally inhibits pontine omnipause neurons, thereby permitting burst neurons to discharge until the saccade is completed. Analysis of large, abnormal saccades calls for application of novel techniques to identify the beginning and end of the saccadic pulse command.

Vestibular and Non-vestibular Contributions to Eye Movements that Compensate for Head Rotations during Viewing of Near Targets

Geometry dictates that when subjects view a near target during head rotation the eyes must rotate more than the head. The relative contribution to this compensatory response by adjustment of the vestibulo-ocular reflex gain (Gvor), visual tracking mechanisms including prediction, and convergence is debated. We studied horizontal eye movements induced by sinusoidal 0.2–2.8xa0Hz, en-bloc yaw rotation as ten normal humans viewed a near target that was either earth-fixed (EFT) or head-fixed (HFT). For EFT, group median gain was 1.49xa0at 0.2xa0Hz declining to 1.08xa0at 2.8xa0Hz. For HFT, group median gain was 0.03xa0at 0.2xa0Hz increasing to 0.71xa0at 2.8xa0Hz. By applying transient head perturbations (peak acceleration >1,000°xa0s−2) during sinusoidal rotation, we determined that Gvor was similar during either EFT or HFT conditions, and contributed only ~75% to the compensatory response. We confirmed that retinal image slip contributed to the compensatory response by demonstrating reduced gain during EFT viewing under strobe illumination. Gain also declined during sum-of-sines head rotations, confirming the contribution of predictive mechanisms. The gain of compensatory eye movements was similar during monocular or binocular viewing, although vergence angle was greater during binocular viewing. Comparison with previous studies indicates that mechanisms for generation of eye rotations during near viewing depend on head stimulus type (rotation or translation), waveform (transient or sinusoidal), and the species being tested.

Effects of visual fixation and convergence on periodic alternating nystagmus due to MS

We studied a young woman with multiple sclerosis, who developed periodic alternating nystagmus (PAN) with a period of oscillation of about three minutes. Neither visual fixation of a stationary target nor large-field optokinetic stimulation substantially influenced the cycle of PAN. During convergence, induced by fixation of a near target, PAN was suppressed by over 70%. Treatment with baclofen abolished her nystagmus, but optokinetic and pursuit responses remained impaired. Convergence during viewing a near target did not increase the response (gain) of her vestibulo-ocular reflex. We postulate that visual drives were able to suppress PAN independently of any effects on vestibular responses and were prevented from exerting effects on velocity storage and vestibular gain adjustment by demyelinating lesions affecting her pontine nuclei and cerebellar circuits.

Disorders of vertical optokinetic nystagmus in patients with ocular misalignment.

PURPOSEnTo compare responses to vertical and horizontal optokinetic (OK) stimulation in patients with disorders of ocular alignment.nnnMETHODSnUsing the magnetic search coil technique, we measured horizontal and vertical rotations of both eyes in six patients with strabismus since childhood and eight normal subjects. The OK stimulus subtended 72 degrees horizontally and 60 degrees vertically, consisted of black-and-white stripes with a spatial frequency of 0.04 cycles/degree, and moved either vertically or horizontally at 22.5 or 12 degrees/s. All patients and controls were tested with both eyes viewing and monocularly.nnnRESULTSnVertical OK responses were asymmetric in most normals and patients. The direction of this asymmetry varied between individuals, but upward stimuli more commonly elicited a greater response than downward stimuli. Monocular horizontal OK responses were symmetric in normals; patients showed either an asymmetry with greater responses for nasal motion, or a directional bias. During monocular and binocular viewing, vertical OK stimulation induced vertical nystagmus in normal subjects, but all patients showed diagonal responses, with horizontal components that were significantly greater than controls. The inappropriate horizontal component of the response increased at the higher stimulus speed, and was not simply due to latent nystagmus.nnnCONCLUSIONSnPatients with disorders of ocular alignment since childhood show an inappropriate horizontal response to vertical OK stimuli, indicating directional abnormality of either motion vision pathways or the ocular motor response.