High-frequency stimulation (HFS) of the subthalamic nucleus (STN) is a well-established therapy for patients with severeParkinson's disease (PD), but its mechanism of action is unclear. Exaggerated oscillatory synchronization in the ␤ (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 ␤ 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 ␤ activity for 12 s after the end of stimulation and a decrease in motor cortical-STN coherence in the ␤ band over the same time period. The reduction in LFP ␤ activity correlated with the movement amplitude during a simple motor task, so that a smaller amount of ␤ 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 ␤ activity in PD.

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Treatment of patients with Parkinson's disease with levodopa has profound effects on both movement and the pattern of movement-related reactivity in the subthalamic nucleus (STN), as reflected in the local field potential (LFP). The most striking change is the promotion of reactivity in the gamma frequency band, but it remains unclear whether the latter is itself a pathological feature, possibly associated with levodopa induced dyskinesias, or is primarily physiological. Gamma band reactivity in the cerebral cortex of humans without Parkinson's disease occurs contralateral to movement, so we posited that lateralization of subcortical gamma reactivity should occur following levodopa if the latter restores a more physiological pattern in patients with Parkinson's disease. Accordingly, we studied movement-related changes in STN LFP activity in 11 Parkinson's disease patients (age 59 +/- 2.7 years, three females) while they performed ipsi- and contralateral self-paced joystick movements ON and OFF levodopa. A bilaterally symmetrical gamma band power increase occurred around movement onset in the OFF state. Following levodopa this feature became significantly more pronounced in the subthalamic region contralateral to movement. The physiological nature of this asymmetric pattern of gamma reactivity was confirmed in the STN of two tremor patients without Parkinson's disease. Although levodopa treatment in the Parkinson's disease patients did not lead to lateralization of power suppression at lower frequencies (8-30 Hz), it did increase the degree of power suppression. These findings suggest that dopaminergic therapy restores a more physiological pattern of reactivity in the STN of patients with Parkinson's disease.

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Depth recordings in patients with Parkinson's disease on dopaminergic therapy have revealed a tendency for oscillatory activity in the basal ganglia that is sharply tuned to frequencies of approximately 70 Hz and increases with voluntary movement. It is unclear whether this activity is essentially physiological and whether it might be involved in arousal processes. Here we demonstrate an oscillatory activity with similar spectral characteristics and motor reactivity in the human thalamus. Depth signals were recorded in 29 patients in whom the ventral intermediate or centromedian nucleus were surgically targeted for deep brain stimulation. Thirteen patients with four different pathologies showed sharply tuned activity centred at approximately 70 Hz in spectra of thalamic local field potential (LFP) recordings. This activity was modulated by movement and, critically, varied over the sleep-wake cycle, being suppressed during slow wave sleep and re-emergent during rapid eye movement sleep, which physiologically bears strong similarities with the waking state. It was enhanced by startle-eliciting stimuli, also consistent with modulation by arousal state. The link between this pattern of thalamic activity and that of similar frequency in the basal ganglia was strengthened by the finding that fast thalamic oscillations were lost in untreated parkinsonian patients, paralleling the behaviour of this activity in the basal ganglia. Furthermore, there was sharply tuned coherence between thalamic and pallidal LFP activity at approximately 70 Hz in eight out of the 11 patients in whom globus pallidus and thalamus were simultaneously implanted. Subcortical oscillatory activity at approximately 70 Hz may be involved in movement and arousal.

No abstract

Visual stimuli are judged for their emotional significance based on two fundamental dimensions, valence and arousal, and may lead to changes in neural and body functions like attention, affect, memory and heart rate. Alterations in behaviour and mood have been encountered in patients with Parkinson's disease (PD) undergoing functional neurosurgery, suggesting that electrical high-frequency stimulation of the subthalamic nucleus (STN) may interfere with emotional information processing. Here, we use the opportunity to directly record neuronal activity from the STN macroelectrodes in patients with PD during presentation of emotionally laden and neutral pictures taken from the International Affective Picture System (IAPS) to further elucidate the role of the STN in emotional processing. We found a significant event-related desynchronization of STN alpha activity with pleasant stimuli that correlated with the individual valence rating of the pictures. Our findings suggest involvement of the human STN in valence-related emotional information processing that can potentially be altered during high-frequency stimulation of the STN in PD leading to behavioural complications.

Depth recordings in patients with Parkinson's disease (PD) have demonstrated exaggerated local field potential (LFP) activity at frequencies between 10 and 30 Hz in the subthalamic nucleus (STN). This activity is modulated prior to single phasic movements, possibly as part of the feedforward organization of incipient voluntary movement, and after single phasic movements, as a consequence of afferent feedback processes. Here we test the hypothesis that this activity is also modulated during repetitive movements, reflecting a role in ongoing performance. Accordingly, we recorded LFP activity from the contralateral STN of seven patients with PD withdrawn from anti-parkinsonian medication while they performed repetitive index finger to thumb taps. Cross-correlograms of LFP activity at different frequencies in the 10-30 Hz band with finger position showed that LFP activity was modulated in amplitude by finger tapping. The modulation was higher at the beginning of each recording when tapping performance was better, and diminished as tapping became more bradykinetic over time. The best modulations were seen over those frequencies that were maximal in the power spectrum of the corresponding LFP, and for a given side were most marked at the contact pair that exhibited the highest power at these frequencies. In conclusion, subthalamic activity in the 10-30-Hz band is amplitude modulated during movement. This process fails as bradykinesia increases.