Oscillatory Activity In Subthalamic Nucleus Research Articles

Single unit and beta oscillatory activities in subthalamic nucleus are modulated during visual choice preference.

Parkinson's disease is a neurodegenerative disease affecting the supply of dopamine to basal ganglia nuclei, leading to pathological beta band (13-35Hz) oscillations in the subthalamic nucleus (STN). STN and beta activity are recognized in motoric functions but their role in cognitive functions remains elusive. We examined single unit and beta local field potential (LFP) activity in the STN during a visual choice preference task in PD patients (n=12) undergoing deep brain stimulation surgery. Patients viewed 2 of 5 possible animal picture-pairs and were instructed to choose their favorite ("fav") picture by clicking the left or right mouse key. A block of trials consisted of 50-75 picture-pair presentations. Single unit histograms and LFP spectrograms were aligned to picture presentation and point of decision for pairs that included the fav and non-fav pictures, respectively. A total of 58 neurons from 26 blocks of trials were analyzed. Thirty of 58 neurons showed a selective change in spiking activity 0.20-0.65s to fav picture presentation, which preceded the shortest recorded reaction time (=0.7s), and 17/58 neurons showed no significant response in our task. Beta LFP significantly desynchronized in response to fav but not non-fav pictures in all trials, and in 14/26 blocks of trials, the desynchronization was followed by a "beta burst" and ramp-up to baseline activity. Neurons with choice preference responses were found throughout the dorsoventral extent of the STN. STN single units and beta activity are modulated during visual choice preference, and this suggests a role for STN beta activity in cognitive processing.

Frequency-Specific Optogenetic Deep Brain Stimulation of Subthalamic Nucleus Improves Parkinsonian Motor Behaviors.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective therapy for the motor symptoms of Parkinson's disease (PD). However, the neural elements mediating symptom relief are unclear. A previous study concluded that direct optogenetic activation of STN neurons was neither necessary nor sufficient for relief of parkinsonian symptoms. However, the kinetics of the channelrhodopsin-2 (ChR2) used for cell-specific activation are too slow to follow the high rates required for effective DBS, and thus the contribution of activation of STN neurons to the therapeutic effects of DBS remains unclear. We quantified the behavioral and neuronal effects of optogenetic STN DBS in female rats following unilateral 6-hydroxydopamine (6-OHDA) lesion using an ultrafast opsin (Chronos). Optogenetic STN DBS at 130 pulses per second (pps) reduced pathologic circling and ameliorated deficits in forelimb stepping similarly to electrical DBS, while optogenetic STN DBS with ChR2 did not produce behavioral effects. As with electrical DBS, optogenetic STN DBS exhibited a strong dependence on stimulation rate; high rates produced symptom relief while low rates were ineffective. High-rate optogenetic DBS generated both increases and decreases in firing rates of single neurons in STN, globus pallidus externa (GPe), and substantia nigra pars reticular (SNr), and disrupted β band oscillatory activity in STN and SNr. High-rate optogenetic STN DBS can indeed ameliorate parkinsonian motor symptoms through reduction of abnormal oscillatory activity in the STN-associated neural circuit, and these results highlight that the kinetic properties of opsins have a strong influence on the effects of optogenetic stimulation.SIGNIFICANCE STATEMENT Whether STN local cells contribute to the therapeutic effects of subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) remains unclear. We re-examined the role of STN local cells in mediating the symptom-relieving effects of STN DBS using cell type-specific optogenetic stimulation with a much faster opsin, Chronos. Direct optogenetic stimulation of STN neurons was effective in treating the symptoms of parkinsonism in the 6-hydroxydopamine (6-OHDA) lesion rat. These results highlight that the kinetic properties of opsins can have a strong influence on the effects of optogenetic activation/inhibition and must be considered when employing optogenetic to study high-rate neural stimulation.

Comparison of oscillatory activity in subthalamic nucleus in Parkinson's disease and dystonia

ObjectivesDeep brain stimulation (DBS) of the subthalamic nucleus (STN) has been successfully used to treat both Parkinson's disease (PD) and dystonia. Local field potentials (LFPs) recorded from the STN of PD patients demonstrate prominent beta frequency band activity. It is unclear whether such activity occurs in the STN in dystonia, and, if not, whether dystonia has another distinctive neural population activity in the STN. MethodsTwelve patients with PD, and eight patients with dystonia underwent DBS electrode implantation targeting the STN. Seven dystonia patients were off medication and one was on aripiprazole and clonazepam. LFPs were recorded from the DBS electrodes in PD in the on/off medication states and in dystonia. Power spectra and temporal dynamics measured by the with Lempel-Ziv complexity of the LFPs were compared among these states. ResultsNormalised power spectra and Lempel-Ziv complexity of subthalamic LFPs differed between dystonia off and PD on/off, and between PD off and on over the low frequency, beta and high gamma bands. Patients with dystonia and off medication had lower beta power but higher low frequency and high gamma power than PD. Spectral power in the low beta frequency (11–20Hz) range was attenuated in medicated PD. ConclusionThe results suggest that dystonia and PD are characterized by different patterns of oscillatory activities even within the same nucleus, and exaggerated beta activity may relate to hypo-dopaminergic status.

Modulation of Beta Oscillations in the Subthalamic Nucleus with Prosaccades and Antisaccades in Parkinson's Disease

Increased oscillations in the beta band are thought to be related to motor symptoms of Parkinson's disease (PD). Previous studies have shown that beta-band desynchronization in the subthalamic nucleus (STN) is reduced just before and during limb movements. While the STN is part of the basal ganglia (BG)-thalamocortical circuit controlling limb movements, it is also part of the BG-brainstem projection controlling saccadic eye movements. Late-stage PD patients have deficits in saccades in addition to difficulties with limb movements arising from impaired functions of the BG. We investigated saccade-related changes in beta-band (15-30 Hz) oscillatory activities in the human STN while PD patients performed visually guided prosaccades and antisaccades, the latter requiring suppression of reflexive responses and volitional initiation of saccades. We recorded local field potentials from deep brain stimulation electrodes implanted in the STN in human PD patients 1-5 d after surgery and compared prosaccades and antisaccades with these and with limb movements. Saccade-related beta-band desynchronizations were observed just before and during saccades in all subjects, suggesting that reduction of beta-band oscillatory activity in the STN is related to preparation and execution of saccades. Furthermore, beta-band desynchronizations for antisaccades started earlier, were sustained for longer periods, were of greater magnitude, and were observed more often than prosaccades. Beta-band desynchronization in the STN may reflect the additional processes associated with suppression of reflexive responses and volitional execution of saccades in the opposite direction.

Movement‐related changes in oscillatory activity in the human subthalamic nucleus: ipsilateral vs. contralateral movements

A voluntary movement is accompanied by a series of changes in neuronal oscillatory activity in the subthalamic nucleus (STN). These changes can be recorded through electrodes implanted for deep brain stimulation to treat Parkinson's disease in the time interval between the surgery and the internalization of the connections to the batteries. Both baseline activity and movement-related changes are different in the 'on' and 'off' medication motor states. In the 'off' state a low frequency activity in the alpha-beta range (8-25 Hz) that dominates the spectrum is interrupted during the movement, while in the 'on' state baseline frequencies are higher and a peri-movement gamma increase (70-80 Hz) is usually observed. Similar changes have been described with electrocorticographic recordings over the primary motor cortex but the gamma increase was only present during contralateral movements. We compared ipsi- and contralateral movement-related changes in STN activity, using a time-frequency analysis of the recordings obtained simultaneously in both STN and the scalp (electroencephalography) during right and left hand movements. The movement-related changes observed in the STN in the 'on' and the 'off' states were similar to those described previously in terms of predominant frequency bands, but we found bilateral changes in the STN during movements of either hand. A contralateral earlier start of the beta STN changes was mostly observed when the moving hand corresponded to the less-affected side, irrespective of hand dominance. These results suggest that movement-related activity in the STN has, by and large, a bilateral representation and probably reflects cortical input.

Raphe neurons and barbiturate induced rhythmic activity in the subthalamic nucleus and ventral tegmental area

A continuous rhythmic discharge in the subthalamic nucleus (STN), lateral habenular nucleus, and ventral tegmental area (VTA) is associated with tremor in cats lightly anesthetized with barbiturate. The pontine raphe nuclei centralis superior and inferior also show barbiturate dependent slow wave and unitary activity. Stimulation of the raphe region produces evoked potentials and synchronization of the oscillatory activity in STN and VTA. The latency of the evoked response is shortest in STN. Extensive raphe lesions abolish the rhythmic activity in STN and VTA, but lesions which do not completely destroy nuclei centralis superior and inferior are not effective. In single cell recordings 81% of 142 cells in the pontine raphe region and medial reticular formation are inhibited following VTA stimulation. Fifty-four percent of 129 cells in the same region were inhibited when tested with STN stimulation. Forty-seven raphe paramedian reticular formation cells showed convergence of inhibitory input from STN, VTA, and contralateral sciatic nerve (Group II and III fibers). Depletion of serotonin with p-chlorophenylalanine did not affect the appearance of barbiturate rhythmic activity. It is concluded that the pontine raphe region is not essential for maintenance of the oscillatory activity in STN and VTA, and that the raphe region is on the output side of the system.