Abstract
BackgroundSchizophrenia patients who are suffering from psychomotor slowing (PS) present reduced levels of spontaneous motor activity, as well as slowing of gait and of fine motor dexterity. These motor abnormalities predict poor clinical outcomes for the patients. Recently, MRI studies have shown both aberrant functional and structural connectivity in schizophrenia patients with PS especially in the basal ganglia and the motor/premotor cortex. Arterial spin labeling imaging (ASL) perfusion MRI allows for quantitative measurement of cerebral blood flow (CBF). We used this approach to assess the difference in resting-state CBF between schizophrenia patients with psychomotor slowing and healthy controls as well as the relationships between CBF and motor symptoms in patients. In the current study, we included patients with moderate to severe PS. We hypothesized the intensity of the motor impairment in the patients would be linked to an abnormal increase of the CBF in several areas of the motor system, including basal ganglia, parietal cortex, and motor/premotor cortex.Methods30 participants (13 healthy controls and 17 schizophrenia patients with PS) took part in an MRI session during which we acquired ASL perfusion MRI. We also evaluated psychomotor slowing in patients using 3 distinct measures (a self-report of motor activity using the International Physical Activity Questionnaire (IPAQ), an observer rating using the Salpêtrière Retardation Rating Scale (SRRS), and an objective measure of the global level of activity using wrist actigraphy). First, we assessed differences between groups in quantitative resting CBF. Then, in patients, we explored the association between the 3 different motor disorder measures and the whole-brain resting CBF.ResultsA group comparison showed significantly increased CBF in the right inferior temporal gyrus in patients compared to healthy controls (two samples t-test: t=3.44, p<0.001 (uncorrected), cluster-level correction (kE=75): p(FWE-corr)=0.028, q(FDR-corr)=0.005). Increased severity of psychomotor slowing as measured by SRRS was associated with higher CBF in a widespread network (Multiple regression Z>4, p<0.001 (uncorrected), cluster-level correction (kE=75) p(FWE-corr)<0.001, q(FDR-corr)<0.001)) including the basal ganglia (i.e. striatum and putamen), the right lateral premotor cortex, bilateral Insulas, anterior cingulate cortices, inferior temporal gyri, parietal cortices, and the right parahippocampus. Both IPAQ and actigraphy failed to correlate with the resting CBF.DiscussionThese findings suggest that schizophrenia patients with PS presented an alteration of the resting cerebral blood flow compared to healthy controls. Moreover, in line with our hypothesis, the severity of the psychomotor slowing seems to be associated with increased blood flow in schizophrenia patients in a large network including basal ganglia, parietal cortex, and lateral premotor cortex. Finally among the 3 distinct measures used in the current study, only the SRRS seems to be associated with an abnormal increase of the cerebral blood flow. These findings confirm that psychomotor slowing is associated with an alteration of the cerebral blood flow in the motor/premotor network. We expect refined results as we include more subjects in the running study.
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