Temporal information processing is a fundamental brain function, which might include central timekeeping mechanisms independent of sensory modality. Psychopharmacological and patient studies suggest a crucial role of the basal ganglia in time estimation. In this study, functional magnetic resonance imaging (fMRI) was applied in 15 healthy right-handed male subjects performing an auditory time estimation task (duration discrimination of tone pairs in the range of 1,000-1,400 ms) and frequency discriminations (tone pairs differing in pitch, around 1,000 Hz) as an active control task. Task difficulty was constantly modulated by an adaptive algorithm (weighted up-down method) reacting on individual performance. Time estimation (vs rest condition) elicited a distinct pattern of cerebral activity, including the right medial and both left and right dorsolateral prefrontal cortices (DLPFC), thalamus, basal ganglia (caudate nucleus and putamen), left anterior cingulate cortex, and superior temporal auditory areas. Most activations showed lateralisation to the right hemisphere and were similar in the frequency discrimination task. Comparing time and frequency tasks, we isolated activation in the right putamen restricted to time estimation only. This result supports the notion of central processing of temporal information associated with basal ganglia activity. Temporal information processing in the brain might thus be a distributed process of interaction between modality-dependent sensory cortical function, the putamen (with a timing-specific function), and additional prefrontal cortical systems related to attention and memory. Further investigations are needed to delineate the differential contributions of the striatum and other areas to timing.
fMRI was performed in nine male schizophrenia patients and 15 healthy male controls during an auditory time estimation (timing), a frequency (i.e. pitch) discrimination task, and rest. An adaptive psychophysical approach, the weighted up-down method, was used to adjust individual performance to a level of 75% probability for correct answers. Although performing on the same level of individual difficulty, schizophrenia patients revealed less activations in prefrontal cortex and caudate nucleus, comparing time vs rest. Timing specific differences (i.e. timing vs pitch) between patients and controls were found in the posterior putamen, anterior thalamus, and right medial prefrontal cortex, with patients showing relative hypoactivity. Impairment in time estimation in schizophrenia might be mediated by specific fronto-thalamo-striatal dysfunction.
The Continuous Performance Test (CPT) has become an essential constituent of the neuropsychological investigation of schizophrenia. Also, a vast number of brain imaging studies, mostly PET investigations, have employed the CPT as a cognitive challenge and established a relative hypofrontality in schizophrenics compared to controls. The aim of the present investigation was to clarify whether this predescribed hypofrontality could also be verified using functional magnetic resonance imaging (fMRI). 20 healthy volunteers and 14 schizophrenics on stable neuroleptic medication were included. Imaging was performed using the CPT-double-T-version and a clinical 1.5 T MRI-scanner with a single slice technique and a T(2)*-weighted gradient-echo-sequence. The schizophrenics exhibited a decreased activation in the right mesial prefrontal cortex, the right cingulate and the left thalamus compared to controls. These results obtained by fMRI are discussed in relation to published findings using PET.
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