Manual dexterity measures can be useful for early detection of age-related functional decline and for prediction of cognitive decline. However, what aspects of sensorimotor function to assess remains unclear. Manual dexterity markers should be able to separate impairments related to cognitive decline from those related to healthy aging. In this pilot study, we aimed to compare manual dexterity components in patients diagnosed with cognitive decline (mean age: 84 years, N = 11) and in age comparable cognitively intact elderly subjects (mean age: 78 years, N = 11). In order to separate impairments due to healthy aging from deficits due to cognitive decline we also included two groups of healthy young adults (mean age: 26 years, N = 10) and middle-aged adults (mean age: 41 years, N = 8). A comprehensive quantitative evaluation of manual dexterity was performed using three tasks: (i) visuomotor force tracking, (ii) isochronous single finger tapping with auditory cues, and (iii) visuomotor multi-finger tapping. Results showed a highly significant increase in force tracking error with increasing age. Subjects with cognitive decline had increased finger tapping variability and reduced ability to select the correct tapping fingers in the multi-finger tapping task compared to cognitively intact elderly subjects. Cognitively intact elderly subjects and those with cognitive decline had prolonged force release and reduced independence of finger movements compared to young adults and middle-aged adults. The findings suggest two different patterns of impaired manual dexterity: one related to cognitive decline and another related to healthy aging. Manual dexterity tasks requiring updating of performance, in accordance with (temporal or spatial) task rules maintained in short-term memory, are particularly affected in cognitive decline. Conversely, tasks requiring online matching of motor output to sensory cues were affected by age, not by cognitive status. Remarkably, no motor impairments were detected in patients with cognitive decline using clinical scales of hand function. The findings may have consequences for the development of manual dexterity markers of cognitive decline.

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.