Abnormalities in both time processing and dopamine (DA) neurotransmission have been observed in schizophrenia. Time processing seems to be linked to DA neurotransmission. The cognitive dysmetria hypothesis postulates that psychosis might be a manifestation of the loss of coordination of mental processes due to impaired timing. The objective of the present study was to analyze timing abilities and their corresponding functional neuroanatomy in schizophrenia. We performed a functional magnetic resonance imaging (fMRI) study using a predictive motor timing paradigm in 28 schizophrenia patients and 27 matched healthy controls (HC). The schizophrenia patients showed accelerated time processing compared to HC; the amount of the acceleration positively correlated with the degree of positive psychotic symptoms and negatively correlated with antipsychotic dose. This dysfunctional predictive timing was associated with BOLD signal activity alterations in several brain networks, especially those previously described as timing networks (basal ganglia, cerebellum, SMA, and insula) and reward networks (hippocampus, amygdala, and NAcc). BOLD signal activity in the cerebellar vermis was negatively associated with accelerated time processing. Several lines of evidence suggest a direct link between DA transmission and the cerebellar vermis that could explain their relevance for the neurobiology of schizophrenia.

• Keywords
• cerebellum, cognitive dysmetria, dopamine, fMRI, predictive timing, schizophrenia,
• MeSH
• Adult MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Brain Mapping MeSH
• Brain physiopathology   MeSH
• Nerve Net physiopathology   MeSH
• Motor Activity physiology   MeSH
• Schizophrenia physiopathology   MeSH
• Cerebellar Vermis physiopathology   MeSH
• Time Perception physiology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: Parkinson's disease (PD) patients are deficient in time estimation. This deficit improves after dopamine (DA) treatment and it has been associated with decreased internal timekeeper speed, disruption of executive function and memory retrieval dysfunction. METHODOLOGY/FINDINGS: The aim of the present study was to explore the neurophysiologic correlates of this deficit. We performed functional magnetic resonance imaging on twelve PD patients while they were performing a time reproduction task (TRT). The TRT consisted of an encoding phase (during which visual stimuli of durations from 5 s to 16.6 s, varied at 8 levels were presented) and a reproduction phase (during which interval durations were reproduced by a button pressing). Patients were scanned twice, once while on their DA medication (ON condition) and once after medication withdrawal (OFF condition). Differences in Blood-Oxygenation-Level-Dependent (BOLD) signal in ON and OFF conditions were evaluated. The time course of activation in the brain areas with different BOLD signal was plotted. There were no significant differences in the behavioral results, but a trend toward overestimation of intervals ≤11.9 s and underestimation of intervals ≥14.1 s in the OFF condition (p<0.088). During the reproduction phase, higher activation in the precuneus was found in the ON condition (p<0.05 corrected). Time course was plotted separately for long (≥14.1 s) and short (≤11.9 s) intervals. Results showed that there was a significant difference only in long intervals, when activity gradually decreased in the OFF, but remained stable in the ON condition. This difference in precuneus activation was not found during random button presses in a control task. CONCLUSIONS/SIGNIFICANCE: Our results show that differences in precuneus activation during retrieval of a remembered duration may underlie some aspects of time perception deficit in PD patients. We suggest that DA medication may allow compensatory activation in the precuneus, which results in a more accurate retrieval of remembered interval duration.

• MeSH
• Behavior physiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging * methods   MeSH
• Brain Mapping methods   MeSH
• Memory MeSH
• Parkinson Disease diagnostic imaging   physiopathology   psychology   MeSH
• Psychomotor Performance physiology   MeSH
• Radiography MeSH
• Aged MeSH
• Oxygen Consumption physiology   MeSH
• Parietal Lobe blood supply   diagnostic imaging   physiopathology   MeSH
• Time Perception physiology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH