Aberrant preparation of hand movement in schizophrenia spectrum disorder: an fMRI study

Abstract

Schizophrenia spectrum disorder is linked to impaired self-other distinction and action feedback monitoring, largely stemming from sensory-motor predictive mechanisms. However, the neural correlates of these predictive processes during movement preparation are unknown. Here, we investigated whether patients with schizophrenia spectrum disorder exhibit aberrant sensory-motor predictive processes reflected in neural activation patterns prior to hand movement onset. Functional MRI data from patients with schizophrenia spectrum disorder (n = 20) and healthy controls (n = 20) were acquired during actively performed or passively induced hand movements. The task required participants to detect temporal delays between their movements and video feedback, which either displayed their own (self) or someone else's (other) hand moving in accordance with their own hand movements. Patients compared with healthy controls showed reduced preparatory blood-oxygen-level-dependent activation (active > passive) in clusters comprising the left putamen, left insula, left thalamus and lobule VIII of the right cerebellum. Reduced activation in the left insula and putamen was specific to own-hand feedback. Additionally, patients with schizophrenia spectrum disorder revealed reduced suppression (passive > active) in bilateral and medial parietal (including the right angular gyrus) and occipital areas, the right postcentral gyrus, cerebellum crus I, as well as the left medial superior frontal gyrus. Ego-disturbances were negatively correlated with left insula and putamen activation during active conditions and with right angular gyrus activation patterns during passive conditions when own-hand feedback was presented. These functional MRI findings suggest that group differences are primarily evident during preparatory processes. Our results show that this preparatory neural activation is further linked to symptom severity, supporting the idea that the preparation of upcoming events as internal predictive mechanisms may underlie severe symptoms in patients with schizophrenia spectrum disorder. These findings could improve our understanding of deficits in action planning, self-monitoring and motor dysfunction in various psychiatric, neurological and neurodegenerative disorders.

Keywords: action-awareness; ego-disturbances; passivity-symptoms; pre-activation; self-other-distinction.

Graphical Abstract

Figure 1

Experimental design. At the beginning of each run (48 trials), participants were instructed either to perform the hand movement during each trial themselves (‘active’ movements) or to relax their wrists and let their hands be moved by the PMD (‘passive’ movements). A trial commenced with a ‘Ready’ cue, followed by visual feedback displaying the participant's own or someone else's hand. Subsequently, the participants were asked to report whether they noticed a delay (‘Delay?’). A black screen with variable duration (2000–5000 ms) was shown during the inter-trial interval. In the preparation period, the participant's hand was at rest (1st frame marked with a green box), as the subject was instructed to move only to execute the hand movement. In the experiment, continuous video feedback was displayed, illustrated in four separate pictures to visualize the entire process of preparation and execution of the different movement directions. From the movement onset point, the hand moved from the left (2nd frame) to the right (3rd frame), and then the hand moved back to the left (shown by the 4th frame) position. Considering male participants for this figure, the upper row shows the sequence of a trial with ‘self’ hand video feedback, while the lower row shows another trial with the ‘other’ hand image from a female person. In the case of a female subject, a male hand image is displayed in the ‘other’ hand video. The self-other hand was displayed randomly across the trials and runs. See the video demonstration available at http://doi.org/10.5281/zenodo.2621302.

Figure 2

Neural activation in active compared with passive condition. (A) activation in healthy control (HC) at Z = −8, X = −10; (B) activation in schizophrenia spectrum disorder (SSD) at Z = 32, X = 8; (C) common activated brain areas between HC and SSD at Z = −4, X = −28; (D) activation specific for HC at Z = −4, X = −20; (E) activation specific for SSD at Z = 62, X = 58; (F) differentiable activated brain area between HC and SSD at Z = −2, X = −30. The performed statistical test is a T-contrast with T-values ranging from 1 to 5. HC, healthy control (n = 20); SSD: schizophrenia spectrum disorder (n = 20).

Figure 3

Neural activation in passive compared to active conditions. (A) activation in healthy control (HC) at Z = 0, X = −22; (B) activation in schizophrenia spectrum disorder (SSD) at Z = 0, X = −52; (C) differentiable activated brain areas between HC and SSD at Z = 32, X = −18; (D) activation specific for HC at Z = 38, X = −16; (E) pre-suppression specific for SSD at Z = −24, X = −52; (F) group-specific differences of activation pattern during preparation than movement execution shown at Z = −4, X = −28. The performed statistical test is a T-contrast with T-values ranging from 1 to 5. HC, healthy control (n = 20); SSD, schizophrenia spectrum disorder (n = 20).

Figure 4

Exploratory correlation of neural activity with positive and negative symptoms. (A) Pre-activation in the left putamen and insula for active conditions with own hand feedback (see Fig. 2F). (B) Pre-activation in the right angular gyrus for passive conditions with own hand feedback. Hallucinations (SAPS questions 1–7), delusions of reference (SAPS question 14), delusions of being controlled (SAPS question 15) and residual positive symptoms (SAPS questions 21–35), affective flattening or blunting (SANS items 1–8), avolition/apathy (SANS items 14–17) and anhedonia/asociality (SANS items 18–22). The error bar represents the standard error mean and reflects a 95% confidence interval calculated from the Pearson correlation coefficient. HC, healthy control (n = 20); SSD, schizophrenia spectrum disorder (n = 20).