Eye Movements May Flag Cognitive Impairment in Schizophrenia

Eye-movement abnormalities may flag specific types of cognitive impairment in schizophrenia patients, new research shows.



A multicenter study found that scanpath length and matrix reasoning were more strongly correlated in patients with schizophrenia than in healthy persons. Matrix reasoning scores are a measure of spatial organization.

"We found a significant association between eye-movement-based measures of visual exploration and cognitive scores requiring visual search in subjects with schizophrenia," Ryota Hashimoto, MD, PhD, of the Japanese National Institute of Mental Health in Tokyo, told Medscape Medical News.

"These findings strengthen the understanding of two distinct impairments known to exist in schizophrenia — visual exploration abnormalities and perceptual organization impairments, both which have been linked to top-down control mechanisms," Hashimoto added.

The study was published online January 17 in Schizophrenia Research.

Relevance Unclear
Eye-movement abnormalities are well documented in patients with schizophrenia. Such abnormalities include visual exploration during free-viewing tasks; loss of gain during smooth pursuit; and difficulties in voluntary control of fixations.

Nevertheless, the relevance of these abnormalities to everyday functioning and cognitive impairment remains unknown, as there have been few studies into the link between eye movement and cognitive ability in patients with schizophrenia.

In 1994, researchers investigated visual exploration patterns using the revised Wechsler Adult Intelligence Scale (WAIS-R) picture-completion test. The study revealed that scanpath lengths were shorter in individuals with schizophrenia than in healthy participants.

Similar results were reported in a study published in 2011. In that study, investigators found that patients with schizophrenia utilized a poor search strategy in a digit-symbol coding task.

Hashimoto and colleagues note that previous research was limited by small sample sizes and few outcome measures and that current understanding of the general relationship between eye-movement abnormalities and cognitive ability in patients with schizophrenia is limited.

To address these shortcomings, the researchers obtained data from the 517 persons who were recruited as part of a large-scale cohort at Osaka University, Japan.

Exclusion criteria were many and varied. No participants had a history of ophthalmologic disease, and all had normal or corrected-to-normal vision. Individuals with schizophrenia had been diagnosed by at least two trained psychiatrists, using the Structured Clinical Interview for DSM-IV.

Three different eye-movement examinations were administered — assessment of scanpath length, horizontal position gain, and duration of fixations. All of these measures had been previously reported to successfully distinguish between people with schizophrenia and healthy persons. These three measures were used to calculate a comprehensive schizophrenia eye score.

The investigators used age-referenced scores from the Japanese version of the WAIS-III to measure patients' cognitive abilities. They utilized full-scale IQ; the WAIS-III's four individual index scores (verbal comprehension, working memory, perceptual organization, and processing speed); and the scaled scores for all 13 subtests: vocabulary, similarity, information, comprehension, arithmetic, digit span, letter-number sequencing, picture completion, block design, matrix reasoning, picture arrangement, digit symbol coding, and symbol search.

Significant Differences
Perhaps not surprisingly, the study showed that for the three individual eye-movement measures (scanpath length, horizontal position gain, and duration of fixations), as well as the integrated eye-movement measure and the WAIS-III, scores differed significantly between healthy individuals and patients with schizophrenia.

Of the three eye-movement measures, scanpath length differed the most between groups.

Scanpath length was significantly correlated with WAIS-III scores. Among individuals with schizophrenia, such correlations were significant between scanpath length and both matrix reasoning score (R = 0.39) and digit symbol coding score (R = 0.33).

By comparison, in volunteers, investigators found significant correlations between scanpath length and verbal comprehension index score (R = 0.20), vocabulary score (R = 0.18), performance speed index score (R = 0.20), and symbol search score (R = 0.19).

On testing for the interaction effects of diagnosis and scanpath length on correlated WAIS-III scores, the researchers found a significant interaction effect only for matrix reasoning, for which there was a stronger relationship in those with schizophrenia than in control persons (coefficient 0.05; 95% confidence interval [CI], 0.03 – 0.07; P = .0000172). This correlation remained significant after controlling for a variety of demographic confounders.

The association between scanpath length and matrix reasoning — a measure of perceptual organization in people with schizophrenia — implies the existence of common cognitive processes, the investigators note.

They also believe these findings strengthen the understanding of two distinct impairments known to exist in patients with schizophrenia — visual-exploration abnormalities and perceptual-organization impairments — both of which have been linked to top-down control mechanisms.

As such, effective visual-exploration strategies may benefit people with schizophrenia by offsetting cognitive impairments in tasks that place high demands on top-down cognitive processes, such as perceptual organization.

Important First Step
Commenting on the findings for Medscape Medical News, Aasef G. Shaikh, MD, PhD, of the Daroff-Dell'Osso Eye Movement Laboratory at Case Western Reserve University, Cleveland, Ohio, said the study represents an important first step in the research chain.

"It's a very important area to look at," said Shaikh, who was not involved in the research. "Eye movements are used extensively as markers for many neurological disorders, and more studies are emerging that look into the effects of different things on eye movements."

He noted that more research is necessary to further refine the nature of the relationship between eye-movement abnormalities and cognitive impairment in schizophrenia patients.

"There is significant heterogeneity when it comes to schizophrenia," he added. "So we don't know if these scanpath abnormalities are specific to certain types of schizophrenia.

"The authors have proposed the phenomenology, but we don't yet have the mechanistic underpinnings," Shaikh added. "Next we need to determine why this type of problem exists."

Hashimoto concluded that cognitive impairments are now considered core features of schizophrenia.

"Our findings of the factors leading to cognitive impairments should help develop an effective treatment to improve cognitive functions that eventually leads social functioning of subjects with schizophrenia," he said.

The study was funded by the Japan Agency for Medical Research and Development, the International Research Center for Neurointelligence at the University of Tokyo Institutes for Advanced Study, the Japanese Ministry of Internal Affairs, Japan's National Institutes of Natural Sciences, and the Grants-in-Aid for Scientific Research. The authors have disclosed no relevant financial relationships.

Schizophr Res. Published online January 17, 2019. Abstract

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