Impaired attentional modulation of sensorimotor control and cortical excitability in schizophrenia

Abstract

Impairments in attentional, working memory and sensorimotor processing have been consistently reported in schizophrenia. However, the interaction between cognitive and sensorimotor impairments and the underlying neural mechanisms remains largely uncharted. We hypothesized that altered attentional processing in patients with schizophrenia, probed through saccadic inhibition, would partly explain impaired sensorimotor control and would be reflected as altered task-dependent modulation of cortical excitability and inhibition. Twenty-five stabilized patients with schizophrenia, 17 unaffected siblings and 25 healthy control subjects were recruited. Subjects performed visuomotor grip force-tracking alone (single-task condition) and with increased cognitive load (dual-task condition). In the dual-task condition, two types of trials were randomly presented: trials with visual distractors (requiring inhibition of saccades) or trials with addition of numbers (requiring saccades and addition). Both dual-task trial types required divided visual attention to the force-tracking target and to the distractor or number. Gaze was measured during force-tracking tasks, and task-dependent modulation of cortical excitability and inhibition were assessed using transcranial magnetic stimulation. In the single-task, patients with schizophrenia showed increased force-tracking error. In dual-task distraction trials, force-tracking error increased further in patients, but not in the other two groups. Patients inhibited fewer saccades to distractors, and the capacity to inhibit saccades explained group differences in force-tracking performance. Cortical excitability at rest was not different between groups and increased for all groups during single-task force-tracking, although, to a greater extent in patients (80%) compared to controls (40%). Compared to single-task force-tracking, the dual-task increased cortical excitability in control subjects, whereas patients showed decreased excitability. Again, the group differences in cortical excitability were no longer significant when failure to inhibit saccades was included as a covariate. Cortical inhibition was reduced in patients in all conditions, and only healthy controls increased inhibition in the dual-task. Siblings had similar force-tracking and gaze performance as controls but showed altered task-related modulation of cortical excitability and inhibition in dual-task conditions. In patients, neuropsychological scores of attention correlated with visuomotor performance and with task-dependant modulation of cortical excitability. Disorganization symptoms were greatest in patients with weakest task-dependent modulation of cortical excitability. This study provides insights into neurobiological mechanisms of impaired sensorimotor control in schizophrenia showing that deficient divided visual attention contributes to impaired visuomotor performance and is reflected in impaired modulation of cortical excitability and inhibition. In siblings, altered modulation of cortical excitability and inhibition is consistent with a genetic risk for cortical abnormality.

Common vs. Distinct Visuomotor Control Deficits in Autism Spectrum Disorder and Schizophrenia

“…Visuomotor force-tracking performance was analyzed using MatlabV9.1 (The MathWorks, Inc., Natick, Massachusetts). Grip force of all participants was downsampled to 100 Hz and smoothed (20 msec sliding window using "root mean square" method; Challis & Kitney, 1990;Carment et al, 2019). Several performance measures were extracted trial-by-trial and grouped for trial type (36 trials × 3 trial-types) to study the effect of cognitive load on tracking performance (Single-task, Dual-DIST, Dual-ADD) for each participant: precision of tracking error (quantified as the root mean square error [RMSE] between the target and the tracking force during the ramp and hold periods); timing of force control (quantified by the onset of force production and of force release relative to the respective target, i.e., the time of the positive [production] or negative [release] peak value of the derivative of the tracking force in the interval of AE500 msec around ramp and release onset); release duration (time taken to abruptly reduce the force from 75% to 25% of the target force).…”

“…Twenty-four patients (6 females, 18 males, mean age AE SD: 29 AE 7 years), fulfilling DSM-V criteria for ASD [American Psychiatric Association, 2013], were recruited in the University Department (SHU) at Sainte-Anne Hospital, Paris, France. For patients with SCZ (6 females, 18 males, age AE SD: 31 AE 9 years) and HCs (6 females, 18 males, age AE SD: 30 AE 7 years), clinical and experimental data were obtained from a previous study [Carment et al, 2019]. All patients were clinically stabilized, with or without a constant dose of atypical antipsychotics for at least 1 month (medicated: SCZ, n = 24; ASD, n = 6).…”

“…All participants performed a visuomotor grip force-tracking task with their right hand according to our previously published protocol (see Fig. 1; Carment et al, 2019). Participants had to match a right-to-left scrolling line (target force) as accurately as possible with their grip force using a vertically moving cursor (instantaneous user force feedback).…”

“…This study aimed at assessing patients with ASD through a visuomotor force-tracking paradigm previously used in patients with SCZ and healthy control participants (HCs) [Teremetz et al, 2014]. Tracking performance was assessed by measures of tracking error, force onset, release onset, and release duration, allowing for a direct comparison of potentially shared vs. distinct deficits in a grip force-tracking paradigm [Carment et al, 2019]. In addition, we investigated the effect of cognitive load on visuomotor performance in ASD vs. SCZ [Carment et al, 2019].…”

“…Tracking performance was assessed by measures of tracking error, force onset, release onset, and release duration, allowing for a direct comparison of potentially shared vs. distinct deficits in a grip force-tracking paradigm [Carment et al, 2019]. In addition, we investigated the effect of cognitive load on visuomotor performance in ASD vs. SCZ [Carment et al, 2019].…”