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High-frequency stimulation (HFS) of the subthalamic nucleus (STN) is a well-established therapy for patients with severe Parkinson's disease (PD), but its mechanism of action is unclear. Exaggerated oscillatory synchronization in the beta (13-30 Hz) frequency band has been associated with bradykinesia in patients with PD. Accordingly, we tested the hypothesis that the clinical benefit exerted by STN HFS is accompanied by suppression of local beta activity. To this end, we explored the after effects of STN HFS on the oscillatory local field potential (LFP) activity recorded from the STN immediately after the cessation of HFS in 11 PD patients. Only patients that demonstrated a temporary persistence of clinical benefit after cessation of HFS were analyzed. STN HFS led to a significant reduction in STN LFP beta activity for 12 s after the end of stimulation and a decrease in motor cortical-STN coherence in the beta band over the same time period. The reduction in LFP beta activity correlated with the movement amplitude during a simple motor task, so that a smaller amount of beta activity was associated with better task performance. These features were absent when power in the 5-12 Hz frequency band was considered. Our findings suggest that HFS may act by modulating pathological patterns of synchronized oscillations, specifically by reduction of pathological beta activity in PD.

Enhanced oscillatory local field potential (LFP) activities over a broad frequency range (5-30 Hz) have been consistently reported from the basal ganglia in patients with Parkinson's disease (PD) and in animal models of this disease. Here we test the hypothesis that these activities may have different functional connotations according to their frequency, by seeking a relatively differentiated distribution within the different functional territories of the subthalamic nucleus (STN). To this end we made intra-operative microelectrode recordings of LFP activities within the STN of 8 PD patients undergoing functional neurosurgery. A significantly larger beta (13-30 Hz) power was found in the dorsolateral part of STN, which is related to motor cortical areas, compared to the ventral (associative/limbic) part of STN. This specific topography was not observed for low frequency activity (5-12 Hz). Our data suggest that the relative distribution of oscillatory activity within the STN of patients with PD may differ according to frequency and confirm previously reported findings that beta activity may provide a functional marker for the 'motor' STN in functional neurosurgery.

Local field potential (LFP) gamma (55-95 Hz) activity has been recorded in the vicinity of the subthalamic nucleus with both microelectrodes and macroelectrodes in patients with Parkinson's disease undergoing functional neurosurgery. Although this activity increases with movement its functional significance remains unknown. We hypothesised that elevations in local gamma activity might be associated with an increase in the capacity of individual spike trains to code information. Changes in the median firing frequency, entropy and baud were determined during spontaneous variations in the level of simultaneously recorded LFP gamma activity in a sample of 31 neurons. The latter were recorded from the zona incerta (n = 5) and subthalamic nucleus (n = 26) in 10 parkinsonian patients. Although 19% of neurons showed a decrease in firing rate, overall there was a net increase in spike frequency and baud of 18.0+/-5.5% and 16.9+/-5.3%, when periods of high gamma were compared to periods of low gamma LFP activity. In contrast, entropy dropped by only 0.8+/-0.2% across the sampled neuronal population during periods of high gamma. All net changes were significant. We conclude that overall there was a net elevation in firing rate and potential information coding capacity, assessed in terms of baud, amongst neurons during periods of elevated gamma LFP activity in the subthalamic region.

Depth recordings in patients with Parkinson's disease (PD) have demonstrated oscillatory activity in the gamma frequency (60-100 Hz) band in local field potentials (LFPs) recorded from the region of the subthalamic nucleus (STN). Although this activity has been hypothesised to contribute to movement preparation, it is unclear to what extent these LFP oscillations arise in the STN and are synchronous with local neuronal discharge. We therefore recorded LFPs and neuronal activity from microelectrodes inserted into the STN in PD patients during functional neurosurgery. Eight sides in seven patients out of 15 sides in 12 patients were identified that had peaks in the gamma band in spectra of LFPs. As microelectrodes descended towards STN, there was a pronounced increase in gamma frequency band LFP activity 1 mm above the line joining the anterior and posterior commissures and 2 mm above the microelectrode defined dorsal border of the STN. Gamma activity dropped again 3 mm below the microelectrode defined dorsal border of the STN. Spike-triggered averages of LFP activity suggested that the discharges of neurons in this region were locked to gamma oscillations in the LFP. Gamma band oscillations in the LFP are therefore likely to represent synchronous activity in populations of neurons in the upper STN and bordering zona incerta of patients with PD.

Activation of the basal ganglia has been shown during the preparation and execution of movement. However, the extent to which the activation during movement is related to efferent processes or feedback-related motor control remains unclear. We used motor imagery (MI), which eliminates peripheral feedback, to further investigate the role of the subthalamic area in the feedforward organization of movement. We recorded local field potential (LPF) activity from the region of the subthalamic nucleus (STN) in eight patients with Parkinson's disease off dopaminergic medication during performance of a warned reaction time task. Patients were instructed to either extend the wrist [motor execution (ME)], to imagine performing the same task without any overt movement (MI), or, in a subgroup, to perform a non-motor visual imagery (VI) task. MI led to event-related desynchronization (ERD) of oscillatory beta activity in the region of the STN in all patients that was similar in frequency, time course and degree to the ERD occurring during ME. The degree of ERD during MI correlated with the ERD in trials of ME and, like ME, was accompanied by a decrease in cortico-STN coherence, so that STN LFP activity during MI was similar to that in ME. The ERD in ME and MI were both significantly larger than the ERD in VI. In contrast, event-related synchronization (ERS) was significantly smaller in trials of MI, and even smaller in trials of VI, than during ME. The data suggest that the activity in the region of the human STN indexed by the ERD during movement is related to the feedforward organization of movement and is relatively independent of peripheral feedback. In contrast, sensorimotor feedback is an important factor in the ERS occurring in the STN area after completion of movement, consistent with a role for this region in trial-to-trial motor learning or the re-establishment of postural set following movements.

Depth recordings in patients with Parkinson's disease (PD) have demonstrated prominent oscillatory activity in the beta frequency (13-35 Hz) band in local field potentials (LFPs) recorded from the region of the subthalamic nucleus (STN). Although this activity has been hypothesized to contribute to bradykinesia, it is unclear to what extent the LFP oscillations arise in the STN and are synchronous with local neuronal discharge. We therefore recorded both LFPs and multi-neuronal activity from microelectrodes inserted into STN in six PD patients (8 sides) during functional neurosurgery. As microelectrodes passed from above STN into STN, there was a pronounced increase in beta frequency band LFP activity. Furthermore, spike-triggered averages of LFP activity suggested that the discharges of neurons in STN were locked to beta oscillations in the LFP. The LFP is therefore likely to represent synchronous activity in populations of neurons in the STN of patients with PD.

Excessive synchronisation of basal ganglia activity at frequencies < 30 Hz is a hallmark of the parkinsonian state, and may contribute to bradykinesia. Accordingly, we electrically stimulated chronically implanted subthalamic macroelectrodes in 10 Parkinson's disease patients, after overnight withdrawal of anti-parkinsonian medication. We compared the effects of stimulation at 0, 5, 10, 15, 20, 25, 30, and ca. 130 Hz by measuring kinesia time (KT) in a tapping task. Although the effects of direct stimulation were small, frequency-response curves demonstrated local peaks at 5-10 Hz and at 20-25 Hz, superimposed upon an overall tendency for KT to reduce with increasing stimulation frequency. This is consistent with the hypothesis that spontaneous activities in these bands might promote bradykinesia.

Declarative memory has been reported to rely on the medial temporal lobe system, whereas non-declarative memory depends on basal ganglia structures. We investigated the functional role of the subthalamic nucleus (STN), a structure closely connected with the basal ganglia for both types of memory. Via deep brain high frequency stimulation (DBS) we manipulated neural activity of the STN in humans. We found that DBS-STN differentially modulated memory performance: declarative memory was impaired, whereas non-declarative memory was improved in the presence of STN-DBS indicating a specific role of the STN in the activation of memory systems., (Copyright 2004 Lippincott Williams & Wilkins)