Adrian G. Lasker

Saccades in Huntington's disease: Initiation defects and distractibility

We recorded saccadic eye movements in patients mildly affected with Huntingtons disease. Most showed an increase in saccade latencies that was greater for saccades made on command than to the sudden appearance of a visual target. All patients showed excessive distractibility during attempted fixation. They had particular difficulty suppressing a saccade to a suddenly appearing visual target when simultaneously trying to initiate a saccade in the opposite direction. Our results are compatible with a posited role of the basal ganglia in both the initiation of volitional saccades and in the maintenance of fixation. Saccade abnormalitie—especially distractibility—are sensitive but probably not specific indicators of Huntingtons disease.

Abnormal ocular motor control in Huntington's disease

We studied eye movements in 50 patients with Huntingtons disease. Fixation was impaired in 73% of patients; such individuals had difficulty in suppressing saccades toward novel visual stimuli. Impaired initiation of saccades was manifest by increased reaction time (89%) and inability to make a saccade without head movement (89%) or blink (35%). Saccades and quick phases of nystagmus were slowed in 62%. Smooth pursuit was abnormal in 60%, and vergence in 33%. The vestibulo-ocular reflex and the ability to hold eccentric gaze were preserved even late in the disease.

Transient torsion during and after saccades.

In five normal subjects, we analyzed uncalled for torsion (blips) during and after horizontal and vertical saccades. Torsion was defined as movement out of Listings plane. During horizontal saccades in downward gaze the abducting eye extorted and the adducting eye intorted. The direction of the blips reversed in upward gaze. Peak torsional amplitudes (up to 1-2 deg) were always reached during saccades; drifts back to Listings plane outlasted the saccades. Torsion of the extorting eye was larger than that of the intorting eye, producing a transient positive cyclovergence. Torsion and cyclovergence evoked by vertical saccades were also stereotyped in each eye, but showed idiosyncratic differences among subjects. We conclude that Listings law is violated during saccades. Transient saccade-evoked torsion might reflect properties of the three-dimensional velocity-to-position integrator and/or the ocular plant.

Ocular motor abnormalities in Huntington's disease

We review here the eye movements in patients with Huntingtons disease (HD), concentrating upon saccades as they show the most prominent abnormalities. Inability to suppress reflexive glances to suddenly appearing novel visual stimuli and delayed initiation of voluntary saccades, including predictive saccades, are early and consistent findings. These two abnormalities can be interpreted in the context of a model, based upon the idea that the frontal lobes and basal ganglia contribute more to the control of voluntary than to reflexive types of saccades. Most patients eventually also show slow saccades but they are most prominent when the disease is early-onset. Slowing of saccades may reflect involvement of both the higher-level cerebral centers that trigger saccades and the areas in the brain stem that produce premotor saccade commands. The study of eye movements in HD has led to a fruitful interaction between basic science and clinical investigation, and has served as a paradigm for examining higher-level defects in saccadic eye movement control in patients with various degenerative, neurological diseases or with focal cerebral hemispheral lesions.

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.

Saccades in Huntington's disease: Slowing and dysmetria

Eye movements were recorded from 20 mildly affected patients with Huntingtons disease (HD) who were divided into two groups, 10 patients with onset of symptoms before age 30 and 10 with onset of symptoms after age 30. In the younger onset group (HD < 30), peak saccade velocities were low (<255 deg/sec for 20-deg saccades) in six of the 10 patients, whereas none of the 10 patients in the older onset group (HD > 30) had peak saccade velocities lower than 300 deg/sec. Latencies for volitional saccades were greater than normal in the HD > 30 group, but were normal for the HD < 30 group. The ability to maintain steady fixation in the face of a distracting visual stimulus was decreased, to the same degree, in both groups of HD patients. In addition, 70% of the HD < 30 group had an affected father, while 70% of the HD > 30 group had an affected mother. These findings suggest that the pathophysiology of the slow saccades, initiation deficit, and excessive distractibility in HD are different.

Saccades in Huntington's disease Predictive tracking and interaction between release of fixation and initiation of saccades

We compared saccadic eye movements in 21 patients with Huntingtons disease (HD) and 21 normal subjects. In a predictive tracking task, HD patients were unable to anticipate normally the timing and location of a visual target that alternated its position predictably (± 10°, 0.5 Hz; mean latency of + 170 msec in HD and -78 msec in normal subjects). HD patients and normal subjects, however, showed comparable decreases in saccade latency (110 msec in HD, 124 msec in normal subjects) when the fixation target was turned off 200 msec before (gap task) versus 200 msec after (overlap task) the appearance of an unexpected peripheral stimulus. Taken together, these findings support the idea that HD patients show greater defects in initiating internally generated than in initiating externally triggered saccades. This dichotomy is likely due to involvement of frontal lobe—basal ganglia structures in HD, with relative sparing of parietal–superior collicular pathways.

Oculomotor Abnormalities in Boys With Tourette Syndrome With and Without ADHD

OBJECTIVE To assess saccadic eye movements in boys with Tourette syndrome (TS) with and without attention-deficit hyperactivity disorder (ADHD), comparing performance with that of an age-matched group of male controls. METHOD Three different saccade tasks (prosaccades, antisaccades, and memory-guided saccades) were used to examine functions necessary for the planning and execution of eye movements, including motor response preparation, response inhibition, and working memory. The study included 14 boys with TS without ADHD (TS-only), 11 boys with TS and ADHD (TS+ADHD), and 10 male controls. RESULTS Latency of prosaccades was prolonged in boys with TS (both with and without ADHD) compared with controls. Variability in prosaccade latency was greater in the groups of boys with TS+ADHD compared with both the TS-only and control groups. Response inhibition errors on both the antisaccade task (directional errors) and memory-guided saccade task (anticipatory errors) were increased in boys with TS+ADHD compared with those with TS-only. There were no significant differences among the three groups in accuracy of memory-guided saccades. CONCLUSIONS Oculomotor findings suggest that TS is associated with delay in initiation of motor response as evidenced by excessive latency on prosaccades. Signs of impaired response inhibition and variability in motor response appear to be associated with the presence of ADHD.

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.

Ocular motor indicators of executive dysfunction in fragile X and Turner syndromes

Fragile X and Turner syndromes are two X-chromosome-related disorders associated with executive function and visual spatial deficits. In the present study, we used ocular motor paradigms to examine evidence that disruption to different neurological pathways underlies these deficits. We tested 17 females with fragile X, 19 females with Turner syndrome, and 40 females with neither disorder who comprised the comparison group. Group differences emerged for both the fragile X and Turner syndrome groups, each relative to the comparison group: Females with fragile X had deficits in generating memory-guided saccades, predictive saccades, and saccades made in the overlap condition of a gap/overlap task. Females with Turner syndrome showed deficits in generating memory-guided saccades, but not during either the predictive saccade or gap/overlap task. Females with Turner syndrome, but not females with fragile X, showed deficits in visually guided saccades and anti-saccades. These findings indicate that different brain regions are affected in the two disorders, and suggest that different pathways lead to the similar cognitive phenotypes described for fragile X and Turner syndromes.