Neuronal Activity of the Human Subthalamic Nucleus in the Parkinsonian and Nonparkinsonian State

Abstract

We recorded resting-state neuronal activity from the human subthalamic nucleus (STN) during functional stereotactic surgeries. By inserting up to five parallel microelectrodes for single- or multiunit recordings and applying statistical spike-sorting methods, we were able to isolate a total of 351 single units in 65 patients with Parkinson's disease (PD) and 33 single units in 9 patients suffering from essential tremor (ET). Among these were 93 pairs of simultaneously recorded neurons in PD and 17 in ET, which were detected either by the same (n = 30) or neighboring microelectrodes (n = 80). Essential tremor is a movement disorder without any known basal ganglia pathology and with normal dopaminergic brain function. By comparing the neuronal activity of the STN in patients suffering from PD and ET we intended to characterize, for the first time, changes of basal ganglia activity in the human disease state that had previously been described in animal models of Parkinson's disease. We found a significant increase in the mean firing rate of STN neurons in PD and a relatively larger fraction of neurons exhibiting burstlike activity compared with ET. The overall proportion of neurons exhibiting intrinsic oscillations or interneuronal synchronization as defined by significant spectral peaks in the auto- or cross-correlations functions did not differ between PD and ET when considering the entire frequency range of 1-100 Hz. The distribution of significant oscillations across the theta (1-8 Hz), alpha (8-12 Hz), beta (12-35 Hz), and gamma band (>35 Hz), however, was uneven in ET and PD, as indicated by a trend in Fisher's exact test (P = 0.05). Oscillations and pairwise synchronizations within the 12- to 35-Hz band were a unique feature of PD. Our results confirm the predictions of the rate model of Parkinson's disease. In addition, they emphasize abnormalities in the patterning and dynamics of neuronal discharges in the parkinsonian STN, which support current concepts of abnormal motor loop oscillations in Parkinson's disease.

Does unilateral basal ganglia activity functionally influence the contralateral side? What we can learn from STN stimulation in patients with Parkinson's disease

“…Several lines of evidence suggest that these results are robust. First, the recording microelectrodes were localized within the STN, as attested by the neuronal activity recorded, which was similar to that previously reported in PD patients (Hutchison et al 1998;Rodriguez-Oroz et al 2001;Steigerwald et al 2008). Second, the location of recorded STN single cells and stimulating electrodes were precisely determined using a validated threedimensional histological deformable BG atlas (Yelnik et al 2007;Bardinet et al 2009).…”

“…Second, neuronal activity was sampled for each period, and epochs of elevated discharge rate were analyzed for bursts using a Poisson surprise analysis (Legendy and Salcman 1985) carried out using a Spike2 script (Degos et al 2005). In this experiment, spike trains with spikes of more than five were considered to be bursts (Steigerwald et al 2008). The mean burst frequency, duration, number of spikes per burst, intraburst frequency, and interburst interval were calculated for each neuron with burst discharges (Steigerwald et al 2008).…”

“…In this experiment, spike trains with spikes of more than five were considered to be bursts (Steigerwald et al 2008). The mean burst frequency, duration, number of spikes per burst, intraburst frequency, and interburst interval were calculated for each neuron with burst discharges (Steigerwald et al 2008). Investigation of neuronal oscillations at the single-neuron level was performed as proposed by Muresan et al (2008).…”

Neural network dynamics in Parkinson's disease

“…Experimental studies have linked synchronization in the basal ganglia-thalamocortical circuit that occurs at frequencies within the 3-10 Hz band [44,120,197,207] and beta band (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) [111,113,175,223] with PD. The beta (13-30 Hz) oscillations are probably driven from the motor areas of the cortex, but at tremor frequencies (i.e.…”

“…In particular, single-unit and/or local field potential (LFP) recordings have demonstrated that the external part of the globus pallidus (GPe) and the subthalamic nucleus (STN) exhibit a tendency to oscillate and synchronize at low frequencies in the parkinsonian state [20,34,130,155,176]. The pathophysiological betafrequency oscillations (13-30 Hz) are thought to be responsible for bradykinesia and rigidity in PD patients [111,113,175,223], whereas the 3-10 Hz oscillations have been associated with tremor [44,120,197,207].…”