The analytical approach, based upon principal components analysis (PCA), extracts multiple spatial covariance patterns from the functional imaging data, which together account for the variability in the combined dataset of patients and controls (Alexander and Moeller, 1994 Moeller et al., 1999). This particular pattern was originally identified using a network model of resting-state brain activity (Eidelberg et al., 1994). In addition to reducing the overactivity of STN neurons, these interventions modulate the activity of an abnormal PD-related metabolic pattern (PDRP) that has been associated with the motor features of the disease (Eckert et al., 2007). Dopaminergic therapy as well as high-frequency deep brain stimulation (DBS) of this structure have been found to reduce both the firing rate and synchronization of STN neurons in PD patients (Levy et al., 2001, 2002 Devos et al., 2004). Moreover, the pattern of discharge from the STN is altered in parkinsonism, with neighbouring neurons shifting from spontaneous firing to synchronized oscillation (Gatev et al., 2006 Wichmann and DeLong, 2006). Indeed, elevated spontaneous STN firing rates have been reported in primate models of parkinsonism and in PD patients undergoing intraoperative single unit recordings from this structure (Hutchison et al., 1998 Sterio et al., 2002 Wichmann and DeLong, 2003). According to this model, in PD, dopamine depletion in the substantia nigra pars compacta (SNc) leads to reduced GPe output and a concomitant increase in STN neuronal activity, which contributes in turn to excessive GPi inhibitory outflow to the thalamus (Wichmann and DeLong, 1998). The output of these nuclei tonically inhibits their target nuclei in the thalamus and the brainstem (Alexander et al., 1990 Parent and Hazrati, 1995 a). the internal globus pallidus (GPi) and the substantia nigra pars reticulata (SNr). Classically, the STN belongs to a reciprocal loop that receives input from and projects to the external globus pallidus (GPe), and sends excitatory projections to the basal ganglia output nuclei, i.e. The subthalamic nucleus (STN) plays a key role in the pathophysiology of Parkinson's disease (PD) by modulating the activity of cortico-striato-pallido-thalamocortical (CSPTC) pathways (Parent and Hazrati, 1995 b Hamani et al., 2004). Subthalamic nucleus, Parkinson's disease, brain metabolism Introduction These pathways are likely to mediate the clinical benefit that is seen following targeted STN interventions for this disease. The findings suggest that the functional pathways associated with motor disability in PD are linked to the STN firing rate. STN firing rates correlated with the activity of the former ( P < 0.007) but not the latter network ( P = 0.39). The activity of both the motor ( P < 0.0001) and the cognitive ( P < 0.006) PD-related metabolic networks was elevated in these patients. Significant correlations ( P < 0.0005) were also evident in the primary motor (BA4) and dorsolateral prefrontal (BA46/10) cortical areas. These measures correlated ( P < 0.007) with glucose metabolism in the putamen and globus pallidus, which receive projections from this structure. Mean firing rates were 47.2 ± 6.1 and 48.7 ± 8.5 Hz for the left and right hemispheres, respectively. We also examined the relationship between firing rate and the activity of metabolic brain networks associated with the motor and cognitive manifestations of the disease. Spontaneous STN firing rates were recorded during surgery and correlated with preoperative regional glucose metabolism on a voxel-by-voxel basis. We scanned 17 PD patients with 18F-fluorodeoxyglucose (FDG) PET to measure resting glucose metabolism before the implantation of STN deep brain stimulation electrodes. However, the relationship of STN firing rate to regional brain function is not known. Overactivity of subthalamic nucleus (STN) neurons is a consistent feature of Parkinson's disease (PD) and is a target of therapy for this disorder.
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