Reduced pupil dilation during action preparation in schizophrenia

Abstract

Impairments in cognitive control-the ability to exert control over thoughts and actions and respond flexibly to the environment-are well-documented in schizophrenia. However, the degree to which experimental task performance reflects true cognitive control impairments or more general alterations in effort, arousal and/or task preparedness is unclear. Pupillary responses can provide insight into these latter factors, as the pupil dilates with degree of cognitive effort and response preparation. In the current study, 16 medicated outpatients with schizophrenia (SZP) and 18 healthy controls performed a task that measures the ability to reactively inhibit and modify a planned action-the double-step task. In this task, participants were required to make a saccade to a visual target. Infrequently, the target jumped to a new location and participants were instructed to rapidly inhibit and change their eye movement plan. Applying a race model of performance, we have previously shown that SZP require more time to inhibit a planned action. In the current analysis, we measured pupil dilation associated with task preparation and found that SZP had a shallower increase in pupil size prior to the onset of the trial. Additionally, reduced magnitude of the pupil response was associated with negative symptom severity in patients. Based on primate neurophysiology and cognitive neuroscience work, we suggest that this blunted pupillary response may reflect abnormalities in a general orienting response or reduced motivational significance of a cue signifying the onset of a preparatory period and that these abnormalities might share an autonomic basis with negative symptoms.

Pupillary aperture is a potential biomarker of movement preparation

“…An ideal biomarker, which is an indicator of biological process or state, should be able to distinguish between the normal and disease state, be non-invasive and objective. Our findings indicate that the pupil size may index saccadic decision time, and may be used as a biomarker for disease with impairments in motor inhibition, for example, in ADHD, schizophrenia and Parkinson’s disease (Chamberlain et al, 2006; Joti et al, 2007; Wang et al, 2016; Thakkar et al, 2018). In short, taking aforementioned neurophysiological, psychopharmacological studies and our present study together, it appears that the FEF and SC strongly influence the pupil dynamics to optimize perisaccadic visual perception and minimize saccade transients (Mostofi et al, 2020).…”

Differential benefits of olanzapine on executive function in schizophrenia patients: Preliminary findings

“…Although our sample sizes are small, as clinical practice moves toward individualized treatment plans, it is critical that biobehavioral measures are sensitive and reliable at an individual level . Further, small sample sizes have long been used when measuring eye‐movements in schizophrenia patients (for recent work see: Meyhofer et al, ; Seymour et al, ; Thakkar et al, ). We use eye‐movement measures in the present study to examine the effect of a drug treatment and demonstrate robust preliminary findings that significant differences can be observed using the antisaccade task.…”

Identification of attention-deficit hyperactivity disorder based on the complexity and symmetricity of pupil diameter

“…This study included 16 subjects diagnosed with adult ADHD and 20 age-, sex-, and intelligence-matched TD subjects 40 . The sample size for this study was determined based on the sample size used in previous studies regarding the relationship between pupil diameter and psychiatric disorders—including ADHD 33 , 76 , 77 . To assess their intelligence levels, all participants were evaluated with the Wechsler Adult Intelligence Scale-Third Edition, revised Japanese edition (WAIS-III), which comprises the intelligence quotient (IQ), verbal IQ (VIQ), and performance IQ (PIQ).…”

“…Baseline LC activity is strongly reflected in pupil diameter 27 – 29 (review in 30 ) because the LC is the common source for both the sympathetic pathway to the pupil dilator muscle and the parasympathetic pathway to the pupil sphincter muscle 31 , 32 . Therefore, pupil diameter can indicate deficits in attention or arousal, as well as imbalances in the exploration–exploitation trade-off in several psychiatric disorders, including schizophrenia 33 , 34 and autism spectrum disorder (ASD) 35 – 38 . In particular, since the deficits of attention and arousal functions are the core symptoms of ADHD, the behaviour of pupil diameter may directly reflect the symptoms/pathology of ADHD 39 , 40 .…”