'Alternate-goal bias' in antisaccades and the influence of expectation

Saccadic performance depends on the requirements of the current trial, but also may be influenced by other trials in the same experiment. This effect of trial context has been investigated most for saccadic error rate and reaction time but seldom for the positional accuracy of saccadic landing points. We investigated whether the direction of saccades towards one goal is affected by the location of a second goal used in other trials in the same experimental block. In our first experiment, landing points ('endpoints') of antisaccades but not prosaccades were shifted towards the location of the alternate goal. This spatial bias decreased with increasing angular separation between the current and alternative goals. In a second experiment, we explored whether expectancy about the goal location was responsible for the biasing of the saccadic endpoint. For this, we used a condition where the saccadic goal randomly changed from one trial to the next between locations on, above or below the horizontal meridian. We modulated the prior probability of the alternate-goal location by showing cues prior to stimulus onset. The results showed that expectation about the possible positions of the saccadic goal is sufficient to bias saccadic endpoints and can account for at least part of this phenomenon of 'alternate-goal bias'.

Line bisection in simulated homonymous hemianopia

Hemianopic patients make a systematic error in line bisection, showing a contra-lesional bias towards their blind side, which is the opposite of that in hemineglect patients. This error has been attributed variously to the visual field defect, to long-term strategic adaptation, or to independent effects of damage to extrastriate cortex. To determine if hemianopic bisection error can occur without the latter two factors, we studied line bisection in healthy subjects with simulated homonymous hemianopia using a gaze-contingent display, with different line-lengths, and with or without markers at both ends of the lines. Simulated homonymous hemianopia did induce a contra-lesional bisection error and this was associated with increased fixations towards the blind field. This error was found with end-marked lines and was greater with very long lines. In a second experiment we showed that eccentric fixation alone produces a similar bisection error and eliminates the effect of line-end markers. We conclude that a homonymous hemianopic field defect alone is sufficient to induce both a contra-lesional line bisection error and previously described alterations in fixation distribution, and does not require long-term adaptation or extrastriate damage.

Eye movement and diffusion tensor imaging analysis of treatment effects in a Niemann-Pick Type C patient

New treatment options for Niemann-Pick Type C (NPC) have recently become available. To assess the efficiency and efficacy of these new treatment markers for disease status and progression are needed. Both the diagnosis and the monitoring of disease progression are challenging and mostly rely on clinical impression and functional testing of horizontal eye movements. Diffusion tensor imaging (DTI) provides information about the microintegrity especially of white matter. We show here in a case report how DTI and measures derived from this imaging method can serve as adjunct quantitative markers for disease management in Niemann-Pick Type C. Two approaches are taken--first, we compare the fractional anisotropy (FA) in the white matter globally between a 29-year-old NPC patient and 18 healthy age-matched controls and show the remarkable difference in FA relatively early in the course of the disease. Second, a voxelwise comparison of FA values reveals where white matter integrity is compromised locally and demonstrate an individualized analysis of FA changes before and after 1year of treatment with Miglustat. This method might be useful in future treatment trials for NPC to assess treatment effects.

Why do humans make antisaccade errors?

Antisaccade errors are attributed to failure to inhibit the habitual prosaccade. We investigated whether the amount of information about the required response the patient has before the trial begins also contributes to error rate. Participants performed antisaccades in five conditions. The traditional design had two goals on the left and right horizontal meridians. In the second condition, stimulus-goal confusability between trials was eliminated by displacing one goal upward. In the third, hemifield uncertainty was eliminated by placing both goals in the same hemifield. In the fourth, goal uncertainty was eliminated by having only one goal, but interspersed with no-go trials. The fifth condition eliminated all uncertainty by having the same goal on every trial. Antisaccade error rate increased by 2% with each additional source of uncertainty, with the main effect being hemifield information, and a trend for stimulus-goal confusability. A control experiment for the effects of increasing angular separation between targets without changing these types of prior response information showed no effects on latency or error rate. We conclude that other factors besides prosaccade inhibition contribute to antisaccade error rates in traditional designs, possibly by modulating the strength of goal activation.

The ocular motor features of adult-onset alexander disease: a case and review of the literature

A 51-year-old Chinese man presented with gaze-evoked nystagmus, impaired smooth pursuit and vestibular ocular reflex cancellation, and saccadic dysmetria, along with a family history suggestive of late-onset autosomal dominant parkinsonism. MRI revealed abnormalities of the medulla and cervical spinal cord typical of adult-onset Alexander disease, and genetic testing showed homozygosity for the p.D295N polymorphic allele in the gene encoding the glial fibrillary acidic protein. A review of the literature shows that ocular signs are frequent in adult-onset Alexander disease, most commonly gaze-evoked nystagmus, pendular nystagmus, and/or oculopalatal myoclonus, and less commonly ptosis, miosis, and saccadic dysmetria. These signs are consistent with the propensity of adult-onset Alexander disease to cause medullary abnormalities on neuroimaging.

Knowing the future: partial foreknowledge effects on the programming of prosaccades and antisaccades

Foreknowledge about the demands of an upcoming trial may be exploited to optimize behavioural responses. In the current study we systematically investigated the benefits of partial foreknowledge--that is, when some but not all aspects of a future trial are known in advance. For this we used an ocular motor paradigm with horizontal prosaccades and antisaccades. Predictable sequences were used to create three partial foreknowledge conditions: one with foreknowledge about the stimulus location only, one with foreknowledge about the task set only, and one with foreknowledge about the direction of the required response only. These were contrasted with a condition of no-foreknowledge and a condition of complete foreknowledge about all three parameters. The results showed that the three types of foreknowledge affected saccadic efficiency differently. While foreknowledge about stimulus-location had no effect on efficiency, task foreknowledge had some effect and response-foreknowledge was as effective as complete foreknowledge. Foreknowledge effects on switch costs followed a similar pattern in general, but were not specific for switching of the trial attribute for which foreknowledge was available. We conclude that partial foreknowledge has a differential effect on efficiency, most consistent with preparatory activation of a motor schema in advance of the stimulus, with consequent benefits for both switched and repeated trials.

Rapid adaptation of visual search in simulated hemianopia

Patients with homonymous hemianopia have altered visual search patterns, but it is unclear how rapidly this develops and whether it reflects a strategic adaptation to altered perception or plastic changes to tissue damage. To study the temporal dynamics of adaptation alone, we used a gaze-contingent display to simulate left or right hemianopia in 10 healthy individuals as they performed 25 visual search trials. Visual search was slower and less accurate in hemianopic than in full-field viewing. With full-field viewing, there were improvements in search speed, fixation density, and number of fixations over the first 9 trials, then stable performance. With hemianopic viewing, there was a rapid shift of fixation into the blind field over the first 5-7 trials, followed by continuing gradual improvements in completion time, number of fixations, and fixation density over all 25 trials. We conclude that in the first minutes after onset of hemianopia, there is a biphasic pattern of adaptation to altered perception: an early rapid qualitative change that shifts visual search into the blind side, followed by more gradual gains in the efficiency of using this new strategy, a pattern that has parallels in other studies of motor learning.

Multiple colonization with S. pneumoniae before and after introduction of the seven-valent conjugated pneumococcal polysaccharide vaccine

Simultaneous carriage of more than one strain of Streptococcus pneumoniae promotes horizontal gene transfer events and may lead to capsule switch and acquisition of antibiotic resistance. We studied the epidemiology of cocolonization with S. pneumoniae before and after introduction of the seven-valent conjugated pneumococcal vaccine (PCV7).

Peroxisome proliferator-activated receptor-(gamma) receptor ligand partially prevents the development of endometrial explants in baboons: a prospective, randomized, placebo-controlled study

A prospective, randomized, placebo-controlled study was conducted in a baboon model to determine if a thiazolidinedione agonist of peroxisome proliferator-activated receptor-gamma, pioglitazone, can impede the development of endometriosis. Endometriosis was induced using laparoscopic, intrapelvic injection of eutopic menstrual endometrium, previously incubated with placebo or pioglitazone for 30 min, in 12 female baboons with a normal pelvis that had undergone at least one menstrual cycle since the time of captivity. At this point, the 12 baboons were randomized into two groups and treated from the day of induction. They received either PBS tablets (n = 6, placebo control, placebo tablets once a day by mouth) or pioglitazone (n = 6, test drug, 7.5 mg by mouth each day). A second and final laparoscopy was performed in the baboons to record the extent of endometriotic lesions between 24 and 42 d after induction (no difference in length of treatment between the two groups, P = 0.38). A videolaparoscopy was performed to document the number and surface area of endometriotic lesions. The surface area and volume of endometriotic lesions were significantly lower in pioglitazone treated baboons than the placebo group (surface area, 48.6 vs. 159.0 mm(2), respectively, P = 0.049; vol, 23.7 vs. 131.8 mm(3), respectively, P = 0.041). The surface area (3.5 vs. 17.8 mm(2), P = 0.017, pioglizatone vs. placebo) and overall number (1.5 vs. 9.5, P = 0.007, pioglizatone vs. placebo) of red lesions were lower in the pioglitazone group. A peroxisome proliferator-activated receptor-gamma ligand, pioglitazone, effectively reduced the initiation of endometriotic disease in the baboon endometriosis model. Using this animal model, we have shown that thiazolidinedione is a promising drug for preventive treatment of endometriosis.

Antisaccades generate two types of saccadic inhibition

To make an antisaccade away from a stimulus, one must also suppress the more reflexive prosaccade to the stimulus. Whether this inhibition is diffuse or specific for saccade direction is not known. We used a paradigm examining inter-trial carry-over effects. Twelve subjects performed sequences of four identical antisaccades followed by sequences of four prosaccades randomly directed at the location of the antisaccade stimulus, the location of the antisaccade goal, or neutral locations. We found two types of persistent antisaccade-related inhibition. First, prosaccades in any direction were delayed only in the first trial after the antisaccades. Second, prosaccades to the location of the antisaccade stimulus were delayed more than all other prosaccades, and this persisted from the first to the fourth subsequent trial. These findings are consistent with both a transient global inhibition and a more sustained focal inhibition specific for the location of the antisaccade stimulus.