Bilateral control of interceptive saccades: evidence from the ipsipulsion of vertical saccades after caudal fastigial inactivation

The caudal fastigial nuclei (cFN) are the output nuclei by which the medio-posterior cerebellum influences the production of saccades toward a visual target. On the basis of the organization of their efferences to the premotor burst neurons and the bilateral control of saccades, the hypothesis was proposed that the same unbalanced activity accounts for the dysmetria of all saccades during cFN unilateral inactivation, regardless of whether the saccade is horizontal, oblique, or vertical. We further tested this hypothesis by studying, in two head-restrained macaques, the effects of unilaterally inactivating the caudal fastigial nucleus on saccades toward a target moving vertically with a constant, increasing or decreasing speed. After local muscimol injection, vertical saccades were deviated horizontally toward the injected side with a magnitude that increased with saccade size. The ipsipulsion indeed depended upon the tested target speed, but not its instantaneous value because it did not increase (decrease) when the target accelerated (decelerated). By subtracting the effect on contralesional horizontal saccades from the effect on ipsilesional ones, we found that the net bilateral effect on horizontal saccades was strongly correlated with the effect on vertical saccades. We explain how this correlation corroborates the bilateral hypothesis and provide arguments against the suggestion that instantaneous saccade velocity would somehow be "encoded" by the discharge of Purkinje cells in the oculomotor vermis.

Horizontal but not vertical saccades enhance memory retrieval: A meta-analysis and systematic review

Saccade-induced retrieval enhancement (SIRE) refers to the phenomenon that actively engaging in horizontal eye movements before recall enhances subsequent memory performance. This effect is thought to be the result of interhemispheric interactions stimulated by saccades. An alternative explanation is that saccades promote memory retrieval by improving top–down attention control. Thus, the mechanisms of SIRE are unclear, and the present meta-analysis quantitatively analysed the effect of saccades on memory performance and examined the mechanisms of SIRE. We searched “Web of Science,” “PubMed,” and “Springer” for peer-reviewed papers using the keywords “eye movements + memory” and “saccades + memory.” Twenty-two papers were included in the final analysis. There was a significant facilitation of horizontal saccades on overall memory performance, with a pooled effect size (Cohen’s d) of 0.45 ( p < .001). However, the overall effect of vertical saccades was not significant ( d = 0.1, p = .14). Moderation analysis showed that the handedness of participants was a significant moderator of SIRE, with strongly right-handed individuals benefitting more from horizontal saccades than non-strongly right-handed individuals ( p < .01). Horizontal saccades improved memory performance, particularly for strongly right-handed individuals. These results support the interhemispheric interaction hypothesis.

Ocular motor biomarkers in Niemann-Pick disease type C: A prospective cross-sectional multicontinental study in 72 patients

Niemann-Pick type C (NPC) is a rare lysosomal storage disorder with ocular motor involvement. In a multi-continental cross-sectional study we characterized ocular motor function in 72 patients from twelve countries by means of video-oculography. We also searched for ocular motor biomarkers interlinking with disease severity. Study protocol comprised reflexive and self-paced saccades, smooth pursuit, and gaze-holding in both planes. 158 healthy controls acted as data comparison. The Modified Disability Rating Scale, Scale for Assessment and Rating of Ataxia, Spinocerebellar Ataxia Functional Index, and Montreal Cognitive Assessment were also performed. In contrast to previous publications and the common belief that the downward saccadic system degenerates to greater extent than the upward one, our measurements of vertical saccades demonstrated that the involvement in both directions was similar. Mean saccadic peak velocity to 20 deg stimulus was 63.5 deg/s (SD, 95% CIs of the mean: 59.5, [47.9-79.2]) in NPC patients and 403.1 deg/s (69.0, [392.0-414.2 deg/s]) in healthy subjects (p<0.001). Downward saccades yielded 51 deg/s (68.9, [32.7-69.3]), whilst upward 78.8 deg/s (65.9, [60.8-96.8]) (p<0.001). Vertical position smooth pursuit gain was 0.649 (0.33, [0.554-0.744]) in NPC and 0.935 (0.149 [0.91-0.959]) in HC (p<0.001). The number of patient-specific saccadic patterns, incl. slow-pursuit like, hypometric and staircase-pattern saccades suggest varying involvement of the saccadic system with fragmentation of the velocity profile as a sign of omnipause neuron dysfunction. Observed compensating strategies, such as blinks to elicit saccades, head and upper body movements to overcome the gaze palsy, should be used clinically to establish a diagnosis. Vertical reflexive saccades were more impaired and slower than self-paced ones. Ocular motor performance depended on age of onset and disease duration. We found that peak velocity and latency of horizontal saccades, vertical saccadic duration and amplitude, and horizontal position smooth pursuit can be used as surrogate parameters for clinical trials, as they showed the strongest correlation to disease severity. By comparing saccadic with pursuit movements, we showed that 98.2% of patients generated vertical saccades (both up and down) that were below the 95% confidence intervals of the controls peak velocity. Only 46.9% of patients had smooth pursuit gain lower than that of 95% of healthy controls. Vertical supranuclear saccade palsy and not vertical supranuclear gaze palsy is the hallmark of NPC disease. The distinction between saccadic and gaze palsy is also important in other neurodegenerative diseases and inborn errors of metabolism with ocular motor involvement, such as progressive supranuclear palsy or Gaucher disease type 3.

A case of Gerstmann-Straussler-Scheinker (GSS) disease with supranuclear gaze palsy

Background Gerstmann-Straussler-Scheinker disease (GSS), an autosomal dominant prion disorder, usually presents as a slowly progressive cerebellar ataxia followed by later cognitive decline. We present a member of the GSS Indiana Kindred with supranuclear palsy, a less common feature in GSS. Case presentation A 42-year-old man presented with 12 months of progressive gait and balance difficulty. Exam was notable for ataxia and cerebellar eye movement abnormalities. Genetic testing revealed a F198S variant in the prion protein (PRNP) gene, the pathological variant of GSS associated with his family, the Indiana kindred. Eighteen months after initial presentation supranuclear palsy developed. Conclusions GSS is a neurodegenerative prion disease with diverse clinical presentations, and exhibits greater variability in disease phenotype compared to other inherited spongiform encephalopathies. GSS should be on the differential for patients with ataxia and supranuclear palsy, and it is important to assess both horizontal and vertical saccades and optokinetic nystagmus in patients with ataxia.

Horizontal and vertical self-paced saccades as a diagnostic marker of traumatic brain injury

Aim: Eye tracking tests to measure horizontal and vertical saccades as a proxy for neural deficits associated with traumatic brain injury (TBI) were evaluated in the present study. Methodology: A total of 287 participants reporting either no TBI, mild, moderate or severe TBI participated in a suite of eye tracking tests to measure horizontal and vertical saccadic performance. Results: The horizontal saccades test offered a sensitivity of 0.77 and a specificity of 0.78, similarly the vertical saccades tests offered a sensitivity of 0.64 and a specificity of 0.65. Conclusion: The results indicated that using eye-tracking technology to measure these metrics offers an objective, reliable and quantifiable way of differentiating between individuals with different severities of TBI, and those without a TBI.

Association Between Vestibular/Ocular Motor Screening (VOMS) and Concussion Recovery Time in Collegiate Participants

Purpose To evaluate the relationship between Vestibular/Ocular Motor Screening (VOMS) change scores and total scores with recovery time after a concussion in collegiate participants. Methods Participants completed the VOMS within 72 hours of concussion diagnosis. The VOMS consists of smooth pursuits, horizontal saccades, vertical saccades, near-point convergence (NPC), horizontal vestibular ocular reflex (VOR), vertical VOR, and visual motions sensitivity (VMS). Prior to the VOMS, athletes rate pre-provocation symptoms for headache, dizziness, nausea and fogginess, and again after each VOMS component on a scale from 0 (none) to 10 (severe) to obtain a total provocation score for each component. Change scores were calculated by subtracting total pre-provocation symptoms from total provocation for each component. Recovery time was defined as the number of days from injury to physician clearance. A Spearman’s rank correlation assessed relationships between recovery time and VOMS outcomes. Results Seventy-six participants (47 male, 29 female; 18.6±2.2 years old) completed the VOMS and took 13.5±5.4 days to recover. Total provocation scores for each VOMS component were associated with recovery time (smooth pursuits r=.36, p<.001; horizontal saccades r=.40, p<.001; vertical saccades r=.40, p<.001; NPC r=.40, p<.001; horizontal VOR r=.38, p=.001; vertical VOR rs=.31, p=.01; VMS rs=.38, p=.001). Only horizontal saccades (r=.37, p=.001), vertical saccades (r=.30, p=.01), and NPC (r=.27, p=.02) change scores were associated with recovery time. Conclusion VOMS total symptom provocation and change scores for vertical saccades, horizontal saccades, and convergence may provide insight into concussion recovery length. Future research should assess the utility of VOMS change scores when evaluating for a concussion.