Motor impairment represents the main clinical feature of Parkinson's disease (PD). Cognitive deficits are also frequently observed in patients with PD, with a prominent involvement of executive functions and visuo-spatial abilities. We used event-related functional MRI (fMRI) and a paradigm based on visual attention and motor inhibition (Go/NoGO-task) to investigate brain activations in 13 patients with early PD in comparison with 11 healthy controls. The two groups did not report behavioural differences in task performance. During motor inhibition (NoGO-effect), PD patients compared to controls showed an increased activation in the prefrontal cortex and in the basal ganglia. They also showed a reduced and less coherent hemodynamic response in the occipital cortex. These results indicate that specific cortico-subcortical functional changes, involving not only the fronto-striatal network but also the temporal-occipital cortex, are already present in patients with early PD and no clinical evidence of cognitive impairment. We discuss our findings in terms of compensatory mechanisms (fronto-striatal changes) and preclinical signs of visuo-perceptual deficits and visual hallucinations.
Parkinson's disease (PD) is a neurodegenerative disorder whose main clinical feature is motor impairment with resting tremor, rigidity and bradikinesia (Gelb et al., 1999). Degeneration of dopaminergic cells in the substantia nigra and ventral tegmental area represents the neuropathological hallmark of PD. This process is typically associated with the presence of characteristic inclusions in the degenerating neurons, the so-called “Lewy bodies”. Additional clinical features, such as cognitive impairment and dementia, are also frequently observed in patients with PD (Aarsland et al., 2001 and Adler, 2005). Previous behavioural (Farina et al., 2000, Pillon et al., 2003 and Zgaljardic et al., 2003) and functional imaging (Cools et al., 2002, Owen et al., 1998 and Owen, 2004) studies in PD have predominantly focussed on the investigation of executive functions. Motor inhibition is also an interesting cognitive function to be explored in PD, as it is supported by neuronal circuits which are typically involved by PD pathology. On the basis of functional imaging results obtained in normal subjects using disjunctive tasks, Rubia et al. (2006) suggested that the basal ganglia play a critical role in the processing of response selection and motor inhibition (Rubia et al., 2006). The idea is that the inhibitory motor response is mediated by the fronto-striato-thalamic loop, which includes the inferior prefrontal cortex, the basal ganglia, the thalamus and the cerebellum for inhibitory control, and the anterior and posterior cingulate gyrus for attentional and error-related processes. Previous behavioural studies in patients with early PD and no cognitive impairment reported the presence of deficits to inhibit ongoing reactions (Dujardin et al., 1999, Franz and Miller, 2002 and Gauggel et al., 2004). Further investigations, using event-related evoked potentials (ERP) and a Go/NoGo paradim, also suggested a selective impairment of inhibitory functions in patients with PD (Bokura et al., 2001 and Bokura et al., 2005). Despite evidences of behavioural and electrophysiological abnormalities of motor inhibition in PD, the neural substrates of such a dysfunction still remains largely unknown. Functional magnetic resonance imaging (fMRI) is a powerful tool which allows regional brain activation to be measured in subjects when performing tasks which engage specific brain functions. In presence of brain pathology, fMRI has the potential to detect abnormal patterns of brain activation, which indirectly reflect the presence and the distribution of tissue abnormalities These fMRI abnormalities are often detectable before the appearance of clinical manifestations, thus providing information on specific brain dysfunctions at a preclinical stage. In this study we used event related fMRI and a Go/NoGo paradigm to investigate motor response and motor inhibition in patients with early PD. Our principal aim was to assess whether functional abnormalities of the fronto-striato-thalamic neuronal network are already detectable in patients with early PD as preclinical features of impairment of higher level functions.
