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Biomedical subjects

D S Zee

Publications and source records attributed to D S Zee.

At least 19 recordsLinked to original sources

Pursuit responses to target steps during ongoing tracking.

Brief smooth eye-velocity responses to target position steps have been reported during smooth pursuit. We investigated position-error responses in eight healthy human subjects, comparing the effects of a step-ramp change in target position when imposed on steady-state smooth pursuit, vestibuloocular reflex (VOR) slow phases, or fixation. During steady-state pursuit or VOR, the target performed a step-ramp movement in the same or in the opposite direction relative to ongoing eye movements. When the step was directed backward relative to steady-state smooth pursuit, eye velocity transiently decreased (1.3 +/- 0.4 degrees /s; average peak change in amplitude +/- SD), beginning about 100 ms after the step. The amplitude of position-error responses varied inversely with the step size. In contrast, there was little or no response in trials with forward steps during steady-state smooth pursuit, when step-ramps were imposed on VOR or when smooth pursuit began from fixation. We hypothesize that during ongoing smooth tracking when a sudden shift in target position is detected the pursuit system compares the direction of ongoing eye velocity with the relative positional error on the retina. In the case of different relative directions between ongoing tracking and a new target eccentricity, a position-error response toward the new target is initiated. Such a mechanism might help the smooth pursuit system to respond better to changes in target direction. These experimental findings were simulated by a mathematical model of smooth pursuit by implementing direction-dependent behavior with a position-error gating mechanism.

Adult↗

Pontine and cerebellar atrophy correlate with clinical disability in SCA2.

Spinocerebellar ataxia type 2 (SCA2) has protean manifestations, and a clinical marker of progression is needed. Although MRI is a promising tool, it is unclear whether the degree of atrophy shown on MRI is correlated with clinical dysfunction. Here the authors used high-resolution volumetric MRI analysis to show that cerebellar and pontine volumes specifically and closely correlate with functional staging scores.

Adult↗

Phoria adaptation after sustained symmetrical convergence: Influence of saccades.

We recorded divergence eye movements after short (4 s) and long (36 s) periods of sustained symmetrical convergence (30 degrees) in nine normal human subjects using the search coil technique. Following the long period of convergence, alignment after the initial 1,250 ms of divergence was more converged than after the short period of convergence, showing short-term "phoria adaptation". The first 1,000 ms of divergence, however, could be slower, faster or relatively unchanged, depending upon the subject. A change in the timing and/or amplitude of associated saccades (which accelerate ongoing vergence) between the long and short stimuli accounted for much of the difference in the rate of divergence. The differences in saccade pattern during early divergence following the long and short periods of convergence may reflect changes in attentional focus (to near or to far).

Adaptation, Physiological↗

Cognitive influences on predictive saccadic tracking.

We have investigated the effects of mental set on predictive capabilities using a saccade square-wave tracking paradigm with ten normal subjects, comparing three amplitudes (10, 20, and 40 degrees ) and five inter-stimulus intervals (ISIs) (400, 500, 625, 1000, and 2000 ms). Subjects were instructed simply to "follow the lights" (passive, reflexive instruction) or explicitly "move your eyes in time with the lights" (active, volitional instruction). Saccades were defined as reflexive (latency>100 ms), predictive (-200 ms<latency<100 ms), or anticipatory (latency<-200 ms). We also calculated arrival time (saccade latency+saccade duration). Instructions had a striking effect on predictive performance. The effects were greatest with the longest ISIs (1000 and 2000 ms) and the largest target displacement (40 degrees ). With the active instruction there were more predictive and anticipatory saccades and with the passive instruction more reflexive saccades. Furthermore, with the active instruction subjects could take into account the duration of the impending saccade so that the eyes would arrive closer to the appearance of the target no matter what the amplitude of the required saccade. In sum, cognitive set, as determined by the specific instructions given to the subject, has a striking effect on predictive saccade behavior, which has important implications for interpreting physiological and imaging correlates of predictive behavior in normals and in patients with neurological disease.

Adult↗

Acute vestibular neuritis: prognosis based upon bedside clinical tests (thrusts and heaves).

We compared bedside tests of vestibulo-ocular function (head thrust and head heave signs) with caloric testing results in 68 patients with acute vestibular neuritis seen at onset and in follow-up for one year. The head thrust and head heave signs each were strong predictors of a decreased probability of recovery, and if both were present, there was a trend for a slower recovery and a further decrease in the probability of recovery. If the head thrust sign was absent, recovery was assured. Our results suggest that careful bedside testing of semicircular canal (head thrust maneuver) and otolith (head heave maneuver) function provides useful information for predicting prognosis in patients with acute vestibular neuritis.

Acute Disease↗

Relative atrophy of the flocculus and ocular motor dysfunction in SCA2 and SCA6.

Two hereditary ataxia syndromes show distinct profiles of region-specific atrophy and ocular motor deficits. Selective pontine atrophy is associated with slowed saccades in ataxin-2 mutations, and selective floccular atrophy is associated with impaired pursuit and gaze-holding abnormalities in Ca(V)2.1 mutations. Although the flocculus seems to be spared relative to the pons in ataxin-2 mutations, and pursuit and gaze-holding appear to be relatively normal, these can be difficult to assess at the bedside, as corrective saccades are also slow and hard to discern. Here, we show the presence of significant floccular atrophy compared with controls in both ataxin-2 and Ca(V)2.1 mutations, which raises the possibility that abnormalities of smooth pursuit or gaze-holding are present in both conditions.

Adult↗

Predictive saccades to a regularly alternating target in cerebellar patients.

Predictive saccade tracking (targets stepping back and forth at frequencies of 1.25 = 1.0 Hz) and self-paced saccades between two stationary targets were measured in patients with cerebellar degeneration and in normal subjects. Cerebellar patients produced similar predictive latencies and generated the same percentage of predictive saccades as did normal subjects. Only the variability in the self-paced saccade paradigm was different between the groups.

Adult↗

Eye-position dependence of torsional velocity during interaural translation, horizontal pursuit, and yaw-axis rotation in humans.

The translational vestibulo-ocular reflex (tVOR) stabilizes an image on the fovea during linear movements of the head. It has been suggested that the tVOR may share pathways with the pursuit system. We asked whether the tVOR and pursuit would be similar in their behavior relative to Listing's Law. We compared torsional eye velocity as a function of vertical orbital position during interaural translation, pursuit, and yaw-axis rotation. We found that the eye-position-dependence of torsion was similar during translation and pursuit, which differed from that during yaw-axis rotation. These findings further support a close relationship between the mechanisms that generate pursuit and the tVOR.

Adult↗

Torsional and horizontal vestibular ocular reflex adaptation: three-dimensional eye movement analysis.

This study used visual-vestibular conflict to effect short-term torsional and horizontal adaptation of the vestibulo-ocular reflex (VOR). Seven normal subjects underwent sinusoidal whole-body rotation about the earth-vertical axis for 40 min (+/- 37 degrees/s, 0.3 Hz) while viewing a stationary radial pattern fixed to the chair (x0 viewing). During adaptation and testing in darkness, the head was pitched either up or down 35 degrees to excite both the horizontal and torsional VOR. The eyes were kept close to zero orbital elevation. Eye movements were recorded with a dual search coil in a three-field magnetic system. VOR gain was determined by averaging peak eye velocity from ten cycles of chair oscillation in complete darkness. The gain of the angular horizontal VOR (response to rotation about the head rostral-caudal axis) was significantly reduced after training in both head orientations. Angular torsional VOR gain (head rotation about the naso-occipital axis) was reduced in both head orientations, but this reached statistical significance only in the head down position. These results suggest that torsional and horizontal VOR gain adaptation, even when elicited together, may be subject to different influences depending upon head orientation. Differences between head up and down could be due to the relatively greater contribution of the horizontal semicircular canals with nose-down pitch. Alternatively, different VOR-adaptation processes could depend on the usual association of the head down posture to near viewing, in which case the torsional VOR is relatively suppressed.

Adaptation, Physiological↗

Interlocking finger test: a bedside screen for parietal lobe dysfunction.

This study sought to determine the utility of an interlocking finger task in screening for parietal lobe dysfunction. The ability of 69 patients to imitate a standardised set of four interlocking finger figures was compared with concurrent performance on formal neurocognitive tests. Poor interlocking finger test scores correlated most highly with standard measures of parietal lobe dysfunction. In addition, an analytical model of parietal dysfunction indicated the interlocking finger test was similar to, if not better than, standard tests of parietal lobe dysfunction. Attempts to imitate these figures should serve as a fast and simple screen of parietal lobe dysfunction.

Adult↗

Cross-axis adaptation of torsional components in the yaw-axis vestibulo-ocular reflex.

The three pairs of semicircular canals within the labyrinth are not perfectly aligned with the pulling directions of the six extraocular muscles. Therefore, for a given head movement, the vestibulo-ocular reflex (VOR) depends upon central neural mechanisms that couple the canals to the muscles with the appropriate functional gains in order to generate a response that rotates the eye the correct amount and around the correct axis. A consequence of these neural connections is a cross-axis adaptive capability, which can be stimulated experimentally when head rotation is around one axis and visual motion about another. From this visual-vestibular conflict the brain infers that the slow-phase eye movement is rotating around the wrong axis. We explored the capability of human cross-axis adaptation, using a short-term training paradigm, to determine if torsional eye movements could be elicited by yaw (horizontal) head rotation (where torsion is normally inappropriate). We applied yaw sinusoidal head rotation (+/-10 degrees, 0.33 Hz) and measured eye movement responses in the dark, and before and after adaptation. The adaptation paradigm lasted 45-60 min, and consisted of the identical head motion, coupled with a moving visual scene that required one of several types of eye movements: (1) torsion alone (-Roll); (2) horizontal/torsional, head right/CW torsion (Yaw-Roll); (3) horizontal/torsional, head right/CCW torsion (Yaw+Roll); (4) horizontal, vertical, torsional combined (Yaw+Pitch-Roll); and (5) horizontal and vertical together (Yaw+Pitch). The largest and most significant changes in torsional amplitude occurred in the Yaw-Roll and Yaw+Roll conditions. We conclude that short-term, cross-axis adaptation of torsion is possible but constrained by the complexity of the adaptation task: smaller torsional components are produced if more than one cross-coupling component is required. In contrast, vertical cross-axis components can be easily trained to occur with yaw head movements.

Adaptation, Physiological↗

On the distribution of fast-phase intervals in optokinetic and vestibular nystagmus.

Histograms of fast-phase intervals in human optokinetic and vestibular nystagmus were generated, and fitted to statistical distributions used in previous studies. The distributions did not depend on stimulation type (optokinetic or vestibular). An inverse Gaussian or a gamma distribution fitted the data better than did a reciprocal Gaussian distribution, but none fitted the data especially well. In some cases, however, the interpretation of these distributions is more physiologically satisfactory than in others. Recommendations are made on which class of models is preferred, and the experiments needed to support the particular models. Our results call into question the validity of previous studies that fit statistical distributions to data sets of a size comparable to ours.

Adult↗

Deficits in the initiation of eye movements in the absence of a visual target in adolescents with high functioning autism.

BACKGROUND: We used ocular motor paradigms to examine whether or not saccades are impaired in individuals with high functioning autism (HFA). METHODS: We recorded eye movements in patients with HFA (n=11), and in normal adolescents (n=11) on anti-saccade, memory-guided saccade (MGS), predictive saccade and gap/overlap tasks. RESULTS: Compared with the normal subjects, patients with HFA had (1) a significantly higher percentage of directional errors on the anti-saccade task (63.2% versus 26.6%), (2) a significantly higher percentage of response suppression errors on a MGS task (60.3% versus 29.5%) and (3) a significantly lower percentage of predictive eye movements on a predictive saccade task. They also showed longer latencies on a MGS task and for all conditions tested on a gap/null/overlap task (fixation target extinguished before, simultaneously, or after the new peripheral target appeared). When the latencies during the gap condition were subtracted from the latencies in the overlap condition, there was no difference between patients and normals. CONCLUSIONS: Abnormalities in ocular motor function in patients with HFA provide preliminary evidence for involvement of a number of brain regions in HFA including the dorsolateral prefrontal cortex (dlPFC) and the frontal eye fields (FEFs) and possibly the basal ganglia and parietal lobes.

Adolescent↗

Oculomotor abnormalities in attention deficit hyperactivity disorder: a preliminary study.

BACKGROUND: Prevailing hypotheses suggest that attention deficit hyperactivity disorder (ADHD) is secondary to dysfunction of motor intentional systems mediated by prefrontal circuitry. Oculomotor paradigms provide a mechanism for examining and localizing dysfunction at the interface between movement and cognition. OBJECTIVE: Three different saccade tasks (reflexive or prosaccades, antisaccades, and memory-guided saccades) were used to examine functions necessary for the planning and the execution of eye movements, including motor response preparation, response inhibition, and working memory. METHODS: The study included 19 children with ADHD, divided into two groups: a group of 8 children on methylphenidate at the time of testing and a group of 11 children not taking any psychoactive medication. Results from the two groups were compared with those from 25 age- and gender-matched normal control children. RESULTS: Both groups of children with ADHD made significantly more directional errors than did controls on the antisaccade task and significantly more anticipatory errors than did controls on the memory-guided saccade task, findings that are consistent with deficits in response inhibition. There were no significant differences in prosaccade latency, although unmedicated children with ADHD showed significantly greater variability in latency on the prosaccade task than did controls. On the memory-guided saccade task there were no significant differences in saccade accuracy; however, unmedicated children with ADHD showed longer saccade latency than did either controls or medicated children with ADHD. CONCLUSIONS: Oculomotor findings suggest that deficits in prefrontal functions, in particular response inhibition, contribute to behavioral abnormalities observed in ADHD. Findings also suggest that the administration of methylphenidate is associated with improvements in the consistency of motor response. Although there were no observed improvements in response inhibition with methylphenidate, conclusions await a design in which subjects complete testing both on and off medication.

Adolescent↗