Background and Hypothesis Sequential saccade planning requires corollary discharge (CD) signals that provide information about the planned landing location of an eye movement. These CD signals may be altered among individuals with schizophrenia (SZ), providing a potential mechanism to explain passivity and anomalous self-experiences broadly. In healthy controls (HC), a key oculomotor CD network transmits CD signals from the thalamus to the frontal eye fields (FEF) and the intraparietal sulcus (IPS) and also remaps signals from FEF to IPS.Study Design Here, we modeled fMRI data using dynamic causal modeling (DCM) to examine patient-control differences in effective connectivity evoked by a double-step (DS) task (30 SZ, 29 HC). The interrogated network was formed from a combination of (1) functionally identified FEF and IPS regions that robustly responded on DS trials and (2) anatomically identified thalamic regions involved in CD transmission. We also examined the relationship between clinical symptoms and effective connectivity parameters associated with task modulation of network pathways.Study Results Network connectivity was indeed modulated by the DS task, which involves CD transmission. More importantly, we found reduced effective connectivity from thalamus to IPS in SZ, which was further correlated with passivity symptom severity.Conclusions These results reaffirm the importance of IPS and thalamocortical connections in oculomotor CD signaling and provide mechanistic insights into CD alterations and consequently agency disturbances in schizophrenia.

BACKGROUND AND HYPOTHESIS:Corollary discharge (CD) signals are "copies" of motor signals sent to sensory areas to predict the corresponding input. They are a posited mechanism enabling one to distinguish actions generated by oneself vs external forces. Consequently, altered CD is a hypothesized mechanism for agency disturbances in psychosis. Previous studies have shown a decreased influence of CD signals on visual perception in individuals with schizophrenia-particularly in those with more severe positive symptoms. We therefore hypothesized that altered CD may be a trans-diagnostic mechanism of psychosis.STUDY DESIGN:We examined oculomotor CD (using the blanking task) in 49 participants with schizophrenia or schizoaffective disorder (SZ), 36 bipolar participants with psychosis (BPP), and 40 healthy controls (HC). Participants made a saccade to a visual target. Upon saccade initiation, the target disappeared and reappeared at a horizontally displaced position. Participants indicated the direction of displacement. With intact CD, participants can make accurate perceptual judgements. Otherwise, participants may use saccade landing site as a proxy of pre-saccadic target to inform perception. Thus, multi-level modeling was used to examine the influence of target displacement and saccade landing site on displacement judgements.STUDY RESULTS:SZ and BPP were equally less sensitive to target displacement than HC. Moreover, regardless of diagnosis, SZ and BPP with more severe positive symptoms were more likely to rely on saccade landing site.CONCLUSIONS:These results suggest that altered CD may be a trans-diagnostic mechanism of psychosis.

An altered use of context and experience to interpret incoming information has been posited to explain schizophrenia symptoms. The visual system can serve as a model system for examining how context and experience guide perception and the neural mechanisms underlying putative alterations. The influence of prior experience on current perception is evident in visual aftereffects, the perception of the “opposite” of a previously viewed stimulus. Aftereffects are associated with neural adaptation and concomitant change in strength of lateral inhibitory connections in visually responsive neurons. In a previous study, we observed stronger aftereffects related to orientation (tilt aftereffects) but not luminance (negative afterimages) in individuals diagnosed with schizophrenia, which we interpreted as potentially suggesting altered cortical (but not subcortical) adaptability and local changes in excitatory-inhibitory interactions. Here, we tested whether stronger tilt aftereffects were specific to individuals with schizophrenia or extended to individuals with bipolar disorder. We measured tilt aftereffects and negative afterimages in 32 individuals with bipolar disorder, and compared aftereffect strength to a previously reported group of 36 individuals with schizophrenia and 22 healthy controls. We observed stronger tilt aftereffects, but not negative afterimages, in individuals with schizophrenia as compared to both controls and individuals with bipolar disorder, who did not differ from each other. These results mitigate concerns that stronger tilt aftereffects in schizophrenia are a consequence of medication or of the psychosocial consequences of a severe mental illness.

Background: Impaired corollary discharge (CD) signalling disrupts the ability to predict the sensory consequences of one's own actions; impaired CD signalling may be specific to schizophrenia or it may also be a transdiagnostic mechanism of psychosis. We sought to assess whether disruptions in oculomotor CD signalling are equally present in schizophrenia and bipolar disorder (BD) with psychotic features, and whether these putative CD disruptions relate to anomalous self-experiences. Methods: We recruited patients with schizophrenia and patients with BD with psychotic features, as well as healthy controls, to complete a double-step saccade task. On each trial, 2 visual targets (T1 and T2) flashed in rapid succession. For half of the trials, participants could use visual information to look at T2. For the other half, looking correctly at T2 required CD. Results: We included 66 patients with schizophrenia, 43 patients with BD with psychotic features, and 37 healthy controls. On trials requiring CD, patient groups were significantly less accurate than controls in localizing T2 (F-2,F-131 = 8.40, p < 0.001). This reduced accuracy was related to difficulty in compensating for variability in the first saccade (F-2,F-131 = 9.11, p < 0.001). Among controls, anomalous self-experiences predicted worse performance (F-1,F- 57 = 14.23, p < 0.001). Limitations: Our sample comprised stable outpatients with relatively low symptom scores, which may limit the generalizability of our results. Conclusion: These results suggest CD impairments may be a marker of predisposition for psychosis. However, observed inconsistencies suggest that this relationship is nuanced.

AbstractIntroductionPathophysiological theories of schizophrenia (SZ) symptoms posit an abnormality in using predictions to guide behavior. One such prediction is based on imminent movements, via corollary discharge signals (CD) that relay information about planned movement kinematics to sensory brain regions. Empirical evidence suggests a reduced influence of sensorimotor predictions in individuals with SZ within multiple sensory systems, including in the visual system. One function of CD in the visual system is to selectively enhance visual sensitivity at the location of planned eye movements (pre‐saccadic attention), thus enabling a prediction of the to‐be‐foveated stimulus. We expected pre‐saccadic attention shifts to be less pronounced in individuals with SZ than in healthy controls (HC), resulting in unexpected sensory consequences of eye movements, which may relate to symptoms than can be explained in the context of altered allocation of attention.MethodsWe examined this question by testing 30 SZ and 30 HC on a pre‐saccadic attention task. On each trial participants made a saccade to a cued location in an array of four stimuli. A discrimination target that was either congruent or incongruent with the cued location was briefly presented after the cue, during saccade preparation. Pre‐saccadic attention was quantified by comparing accuracy on congruent trials to incongruent trials within the interval preceding the saccade.ResultsAlthough SZs were less accurate overall, the magnitude of the pre‐saccadic attention effect generally did not differ across groups nor show a convincing relationship with symptom severity. We did, however, observe that SZ had reduced pre‐saccadic attention effects when the discrimination target (probe) was presented at early stages of saccade planning, when pre‐saccadic attention effects first emerged in HC.ConclusionThese findings suggest generally intact pre‐saccadic shifts of attention in SZ, albeit slightly delayed. Results contribute to our understanding of altered sensory predictions in people with schizophrenia.

To accommodate for our limited visual working memory (VWM) capacity, an attentional filter ensures only goal-consistent information is encoded into VWM. Despite its critical role in dynamic visual behavior, attentional filtering has traditionally been studied in contexts that restrict eye movements. Critically, saccades have been demonstrated to disrupt perception and object-location binding. Does control over the attentional filter persist across saccades, or do saccades disrupt this filter, resulting in the momentary loss of control post-saccade? In E1 (N=15), we established attentional filtering using a no-saccade design. On each trial, participants fixated on a point in one of four locations before seeing a black shape cue indicating that trial’s target shape (either a square or circle). Following a variable delay, they briefly viewed an array of four colored shapes—either two circles and two squares (2 targets/2 non-targets), or all four of the target shape—and were told to remember the colors of all the target-matching shapes. One of the target-matching shapes was then probed for report, and participants reported its color by clicking on a continuous color wheel. As predicted, we observed effective filtering: performance was better (i.e., less color report error) when only two items were relevant (SS2) relative to when all four were relevant (SS4). In E2 (N=20), we tested whether this filtering was disrupted by a saccade. On some trials, following the initial target shape cue, participants were prompted to make a saccade, and the stimulus array then appeared after either a short (50ms) or long (400ms) post-saccade delay. We observed significantly disrupted attentional filtering immediately following a saccade (short post-saccadic delay), whereas the filter was successfully reinstated following the long post-saccadic delay. We suggest that saccades disrupt attentional filtering and the filter must be reinstated following a saccade to efficiently filter non-targets from VWM encoding.