In this study, we investigated oculomotor behavior in schizophrenia patients and healthy controls during natural behavior, where participants could freely move their eyes, head, and body. For specific oculomotor parameters, such as fixation duration and frequency, we found significant differences between the groups. Some of these differences resembled those reported under laboratory conditions, such as decreased exploratory eye movements [8, 9], while others (e.g., tracking eye movement gain) seem to reach normal performance during natural vision. This might be a characteristic feature of eye-movement behavior in real-life environments which possibly trigger as of yet unknown compensatory mechanisms.
Saccades
In task I, subjects had to successively fixate predefined targets in a self-chosen serial order. Similar to results obtained from experiments in a laboratory environment [6, 7], we found a systematic saccadic undershoot in schizophrenia patients. Other studies performed in laboratory environments did not find shortened saccade amplitudes [41] or reported even an overshoot [42]. A possible explanation for these seemingly contradictory results could be the discrete ranges of saccadic amplitudes employed in the different studies. While Schmid-Burgk and colleagues [6, 7] analyzed a variety of saccadic amplitudes, Levin et al. [41] did not analyze each amplitude range separately for its accuracy. This latter approach might have concealed an undershoot for certain saccade amplitudes. When considering the full range of amplitudes, we found no significant difference of peak velocity between patients and controls. When splitting analysis by saccade amplitudes, however, our results during free gaze showed the most prominent differences in saccade peak velocity between patients and controls for small amplitudes (i.e., 1°–3°). This latter amplitude range is most common during natural vision [35] but rarely examined in laboratory settings. Hence, our present results, at least to some extent, reconcile the apparently conflicting findings in the literature.
The main-sequence of saccades only showed significant differences between patients and controls when comparing all saccades during all tasks. The slightly worse R
2 values in schizophrenia patients could mainly be attributed to the higher variability of saccade parameters within the patient cohort (see standard deviations of saccade amplitudes and peak velocities in Table 2) due to the heterogeneity of the disease. The fit parameters of the power functions indicated an initially steeper slope of functions obtained from patients, which levels out and eventually drops below the level of healthy controls. This functional characteristic might be further evidence that the examined saccade amplitude ranges play a crucial role when studying saccades of schizophrenic patients.
Our results indicate a general impairment of visually guided saccades in schizophrenia patients, which has also been deduced from fMRI findings showing a decreased activation in supplementary and frontal eye fields during saccades [43, 44]. Other studies suggested an impaired prediction of the sensory consequences of one’s own actions [45] and deficient self-monitoring in schizophrenia patients [46], which might result in an incorrect saccade planning. This is supported by studies indicating a generally impaired efference copy mechanism in patients with schizophrenia [47–49]. The negative correlation of the saccade amplitude with the severity of symptoms in our study is in line with these findings and offers an explanation for the observed saccadic undershoot during task I in schizophrenia. In our current study, however, differences in saccade parameters between patients and controls largely depended on the amplitude range under consideration. This amplitude-dependent impairment and its normalization in certain ranges demonstrate the ability of patients to compensate, at least partially, for oculomotor inaccuracies during free natural vision.
Fixation
Oculomotor parameters such as fixation duration and fixation frequency were differently influenced by the behavioral task or the presence or absence of predefined targets. During free gaze and without any additional behavioral task, patients fixated significantly longer and less often than healthy controls. This is in line with a recent study by Egaña et al. [9], investigating free viewing of natural images in the laboratory. In our study, median fixation duration was correlated with the PANSS item grandiosity in schizophrenia patients, indicating that some patients might have drifted off in their imagination during this task. During the fixation of given targets and the instruction to look at them in a self-chosen and self-paced order, however, patients leaped from target to target more than twice as fast as compared to healthy controls. This performance was significantly correlated with anxiety in schizophrenia patients leading to even shorter fixation durations and more fixations per second the more anxious a patient was. However, the observed differences between the tasks were mainly due to a task-specific change in the median fixation duration of healthy controls, while schizophrenia patients fixated almost equally long in both tasks. These results could be based on different bottom-up and top-down processing of visual and non-visual information in schizophrenia patients and healthy controls. It has been argued, for example, that the deployment of attention, for which gaze allocation is a proxy [50, 51], is altered in patients with schizophrenia. Various studies have shown a higher distractibility [52] or the inability to focus attention on salient cues [53] in schizophrenia patients. Yet, the lack of difference in fixation duration during task I and task II in schizophrenia patients of our study implies a more subtle influence of attention and task demands on patients as compared to controls. This suggests that alteration of task performance is differently modulated in patients with schizophrenia and that top-down influences might be less influential for their behavior as compared to healthy controls.
Overall eye-movement patterns of schizophrenia patients showed less exploratory behavior such as saccades to the periphery. This result might be indicative for a generally lower interest of patients in exploring their environment. Earlier studies showed similarly decreased exploratory eye movements in schizophrenia patients in laboratory settings [8, 9] or during unfamiliar tasks in a real-life scenario [10]. We show that this finding is also valid during natural vision in everyday life and therefore might influence perception as a whole in schizophrenia patients.
Tracking eye movements
The analysis of the visual tracking of a stationary target on the ground during self-motion revealed an unexpected result. Although related to smooth-pursuit eye movements (i.e., keeping a visually moving object stationary on the retina), we could not find the typical reduced tracking gain, which has been reported for schizophrenia patients and even their first-degree relatives under laboratory conditions [1–4, 6]. Instead, patients and controls revealed high gain tracking of stationary targets and freely chosen objects. Active tracking of optic flow elements with a gain of almost 1.0 has previously been described under laboratory conditions for healthy subjects [14]. Our current findings indicate that patients might be able to partly compensate for their poor tracking performance during smooth pursuit in the laboratory, e.g., using additional sensory cues (optic flow, vestibular signals) when tracking a target in a real-world environment. This view is supported by Holzman [54], who identified the main source of poor tracking performance in schizophrenia patients as a deficit in velocity sensitivity. In his study, the velocity discrimination of patients got worse when additional non-velocity stimulus cues were eliminated and subjects were forced to rely solely on velocity cues. In natural behavior, several sensory and motor signals interact (e.g., a combination of pursuit and vergence eye movements), which might aid the visual and oculomotor system during target tracking. Additionally, in our paradigm, head movements may have compensated for the otherwise impaired tracking gain. This idea is supported by a recent study which showed abnormal eye–head coordination in schizophrenia patients expressed by an uneconomic over-performance of head movements [55]. Finally, a generally higher demand during natural tasks might have influenced the tracking performance of schizophrenic patients. Shagass and colleagues [56] showed that smooth-pursuit gain in the laboratory improved significantly when the patients had to read numbers shown on the tracking target. The authors argued that the improved gain was due to an increased attentional load, which might also apply to tracking eye movements in natural environments.
Contrary to the gain-tracking performance, the RMSEs of the foveal velocity differed significantly between schizophrenia patients and healthy controls. This result suggests a generally more imprecise tracking with numerous small deviations from an optimal tracking behavior in patients with schizophrenia.
Since re-inviting the same cohort of patients to laboratory measurements was not feasible, we compared the real-world data to common findings from laboratory data reported in the literature. It is self-evident that there is no one-to-one mapping between such tasks.
For example, smooth-pursuit eye movements with fixed head in the laboratory and tracking (eye)movements in the real world serve the same purpose: keep a visually moving object stationary on the retina. However, in the former case only, the eyes are moving, whereas in the latter, eye, head, and possibly body contribute. Hence, the real-world situation requires a higher level of integration, but also offers mechanisms for compensation. To further investigate the differences in tracking performance and the possible contribution of head movements and additional sensory signals, a future study could analyze the tracking of a thrown object while participants are not moving. This type of experiment might be more comparable to smooth pursuit in the laboratory and might reduce the gap between the reported reduced gain in the literature and the real-world data in our study.
Another challenge for comparing data between studies—and even for between-subject designs in the same study—is the heterogeneity of schizophrenia, which is further amplified by potential effects of medication. These limitations notwithstanding, any differences between our results and studies performed in the laboratory may suggest the influence of as of yet unknown distinct or additional mechanisms to eye movements of schizophrenia patients in natural environments, which would point toward new research objectives of future studies and will help to complement the overall picture of this disease.
Schizophrenia patients perform worse in a variety of visual motion tasks, such as discrimination of velocity [57] and motion direction [20], localization and visual backward masking tasks [58]. This may be caused by a dysfunction in areas of the visual motion system, i.e., among others in human middle temporal area (MT) and MST [20, 59], respectively. A dysfunction in those areas in schizophrenia patients could also contribute to the more noisy tracking behavior in our study. Studies in non-human primates implicate that another area of the parietal cortex, the ventral intraparietal area (VIP), is critically involved in the encoding of self-motion [23, 60, 61] and smooth-pursuit eye movements by guiding and coordinating smooth eye and head movements within near-extrapersonal space [62–64]. A functional equivalent of macaque VIP has been identified in human [22]. Accordingly, human area VIP might also play a crucial role in the observed eye-movement dysfunction in schizophrenia patients. This view is supported by Chen et al. [20] who showed a global, but not local, motion processing deficit in patients with schizophrenia. The contribution of multisensory areas like area VIP [65] to the eye-movement behavior in schizophrenia patients might have been hidden in most previously conducted laboratory studies and becomes especially interesting in natural contexts by providing and combining additional sensory information. Hence, further investigations of a functional impairment of the areas within the parietal cortex of schizophrenia patients are needed to better understand the observed eye-movement deviations from healthy controls during natural behavior.
In conclusion, the study of eye movements in natural environments showed differences in basic eye-movement parameters between schizophrenia patients and healthy controls during simple everyday tasks, which were strongly modulated by the task demands. Furthermore, our data suggest that patients can overcome some oculomotor impairments, which become obvious in laboratory studies (e.g., reduced gain during tracking eye movements), by as yet unknown compensatory mechanisms or strategies. These might include an improvement in performance due to higher task engagement and additional sensory input (optic flow, vestibular signals) during natural tasks as well as the possibility to perform unrestricted head movements. Being aware of the multitude of differences between our real-world tasks and typical laboratory measurements, our results provide a first step toward analyzing real-world oculomotor behavior in schizophrenia. Teasing apart the sources of differences and commonalities between laboratory results and real-world data will be an important issue for future research. In any case, our results underline the need to complement laboratory experiments with real-word data (and vice versa) in order to achieve a complete picture of oculomotor dysfunctions in schizophrenia and their implications for patients’ activities of daily living.