Search

Abstract: The pedunculopontine nucleus (PPN) has recently been introduced as a new therapeutic target for deep brain stimulation (DBS) in patients suffering from Parkinson''s disease (PD). In a recent case report it was demonstrated that alpha frequency oscillations appear in PPN after the administration of levodopa in PD, indicating a possible physiological role of these oscillations. Here we confirm this result and investigate the functional connectivity and reactivity of subcortical alpha activity by recording LFP activity from the PPN area and EEG in six patients with PD while at rest and in four of them while they performed ipsi- and contralateral self-paced joystick movements. Levodopa strongly promoted 7–11 Hz oscillatory synchronization in the region of PPN and coupling of this activity with similar activity in the cortical EEG. Such coupling was bidirectional. Moreover, the 7–11 Hz oscillatory synchronization in the PPN area increased about 3 s prior to self-paced movements, but only following levodopa treatment. These findings suggest that alpha oscillations in the PPN area may represent a physiological pattern of activity. The subcortical oscillations are coupled to cortical alpha activity and possibly allied to motor related attentional processes. [Copyright &y& Elsevier]

The pattern of neuronal discharge within the basal ganglia is disturbed in Parkinson''s disease (PD). In particular, there is a tendency for neuronal elements to synchronise at around 20 Hz in the absence of dopaminergic treatment, whereas this activity can be replaced by spontaneous synchronisation at much higher frequencies (>70 Hz) following dopaminergic treatment [J. Neurosci. 21 (2001) 1033; Brain 126 (2003) 2153]. In two PD patients (3 sides), we show that stimulating the subthalamic area at around 20 Hz exacerbates synchronisation at similar frequencies in the globus pallidus interna, the major output structure of the human basal ganglia. In contrast, stimulating the subthalamic area at >70 Hz suppresses pallidal activity at about 20 Hz. Clinically, stimulation of the subthalamic area at similar high frequencies reverses parkinsonism and forms the basis of therapeutic deep brain stimulation in PD. The results point to a possible common mechanism by which both dopaminergic treatment associated synchronisation of subthalamic activity at very high frequency and synchronisation imposed by therapeutic stimulation of the subthalamic area inhibit an abnormal and potentially deleterious synchronisation of basal ganglia output at around 20 Hz. If this activity is unchecked by synchronisation at higher frequency, then pathological 20-Hz oscillations may cascade through the basal ganglia, increasing at subsequent levels of processing. [Copyright &y& Elsevier]

Abstract: Levodopa induced dyskinesias (LIDs) are poorly understood and yet are a major cause of disability in Parkinson''s disease (PD). The activity of neurons in the basal ganglia of patients with PD tends to be strongly synchronized at frequencies under 30 Hz, leading to oscillatory local field potentials (LFPs). As dopaminergic therapy acutely suppresses this synchronization, we investigated whether this suppression may contribute to LIDs. Accordingly, we sought an inverse correlation between oscillatory synchronization and dyskinesia activity across time. To this end, we recorded pallidal LFPs in two Parkinsonian subjects exhibiting LIDs following surgery for deep brain stimulation. We correlated LFP power with simultaneously recorded EMG from the dyskinetic contralateral upper limb. We found highly significant inverse correlations between the oscillatory LFP activity under 30 Hz and dyskinetic EMG (maximum r = −0.65, P < 0.001 and r = −0.33, P < 0.001 for activities over 13–30 Hz in each subject). The inverse relationship between oscillatory pallidal LFP activity and dyskinetic EMG was maintained over time periods of a few seconds and was focal. This observation links the suppression of oscillatory synchronization in the pallidum with dyskinetic muscle activity in PD. [Copyright &y& Elsevier]