Impaired Fixation-Related Theta Modulation Predicts Reduced Visual Span and Guided Search Deficits in Schizophrenia

Abstract

During normal visual behavior, individuals scan the environment through a series of saccades and fixations. At each fixation, the phase of ongoing rhythmic neural oscillations is reset, thereby increasing efficiency of subsequent visual processing. This phase-reset is reflected in the generation of a fixation-related potential (FRP). Here, we evaluate the integrity of theta phase-reset/FRP generation and Guided Visual Search task in schizophrenia. Subjects performed serial and parallel versions of the task. An initial study (15 healthy controls (HC)/15 schizophrenia patients (SCZ)) investigated behavioral performance parametrically across stimulus features and set-sizes. A subsequent study (25-HC/25-SCZ) evaluated integrity of search-related FRP generation relative to search performance and evaluated visual span size as an index of parafoveal processing. Search times were significantly increased for patients versus controls across all conditions. Furthermore, significantly, deficits were observed for fixation-related theta phase-reset across conditions, that fully predicted impaired reduced visual span and search performance and correlated with impaired visual components of neurocognitive processing. By contrast, overall search strategy was similar between groups. Deficits in theta phase-reset mechanisms are increasingly documented across sensory modalities in schizophrenia. Here, we demonstrate that deficits in fixation-related theta phase-reset during naturalistic visual processing underlie impaired efficiency of early visual function in schizophrenia.

Keywords: eye movements; fixation-related potential (FRP); intertrial coherence; visual search.

Figure 1

(A) Example search paths from a representative control and patient with performance similar to the group mean. Circles represent random-search fixations, with diameter representing fixation duration. Gray squares represent prefinal fixation. Thick black circles show final fixation on target. Dashed circle indicates location of the target stimulus. (B) Pilot Behavior Study results. Mean (SEM) search time per search-field as a function of set-size during serial search (note log RT scale). In rmANOVA across conditions by subject, a significant effect of group (P = 0.001) and a significant linear effect of density (P < 0.0001) were observed the group X density effect was nonsignificant (P = 0.7) **P < 0.01 across densities.

Figure 2

Behavioral performance during serial search in the NS. (A) Mean (SEM) time per search-field in controls (Ctl) and patients (Pat). (B) Mean number of fixations per search-field. (C) Mean fixation duration. (D) Mean distance between prefinal and final fixation locations and center of the target. The horizontal reference line indicates the border between foveal and parafoveal processing. (E) Scatter plot showing the relationship between Prefinal distance and Search time across groups. The correlation was significant both across groups covaried for group (shown) and in patients alone (P < 0.001). In a separate ANCOVA, the group X covariate interaction was nonsignificant (F_1,45 = 2.67, P = 0.11) indicating similar slope across groups. **P < 0.01 patient versus control.

Figure 3

Mean occipitoparietal activity to fixation onset for Random-search (top row), prefinal (middle row) and Final (bottom row) fixations. Electrodes used for average: CPz, Pz, POz, P1/P2, and PO3/4. (A) Time–domain potentials showing fixation P1_f and P3_f potentials, scalp distribution (“headmaps”) and corresponding integration windows. Headmaps for Prefinal fixations were highly similar to those of Random and were omitted. (B–D) TF analyses showing mean evoked amplitude (B), ITC (C) and single-trial analysis amplitude (D) for controls and patients. The black horizontal line indicates transition from 3- to 6-cycle Morlet waveform used in analysis. The red box indicates the integration window for P1_f -related theta analyses. The black box indicates the fixation window for P3_f -related delta analyses.

Figure 4

Mean (SEM) FRP-related values from the serial search task as a function of fixation type across groups. (A) Evoked Theta amplitude (corresponding to P1_f). (B) Theta ITC. (C) Single-trial theta amplitude. (D) Evoked delta-amplitude (corresponding to P3_f). (E) Correlation between evoked theta amplitude and search time in patients. (F) Correlation between evoked theta amplitude and prefinal fixation distance in patients.

Figure 5

Fixation analyses. (A,B) Distributions of prefinal fixation distances to the target for the serial and parallel-search tasks for controls (A) and patients (B). (C) Correlation between prefinal distances on the serial and parallel-search tasks, across groups. (D) Correlation between patients vs. controls fixation time as a function of grid location. (E) Relative number of fixations to low- and high-contrast distractors in patients and controls. ***P < 0.000. (F) Percentage of fixations on low-contrast stimuli for both groups, showing no significant difference between groups.