Subthalamic Nucleus Activity Research Articles

Vocal emotion decoding in the subthalamic nucleus: An intracranial ERP study in Parkinson’s disease

Using intracranial local field potential (LFP) recordings in patients with Parkinson’s disease (PD) undergoing deep brain stimulation (DBS), we explored the electrophysiological activity of the subthalamic nucleus (STN) in response to emotional stimuli in the auditory modality. Previous studies focused on the influence of visual stimuli. To this end, we recorded LFPs within the STN in response to angry, happy, and neutral prosodies in 13 patients with PD who had just undergone implantation of DBS electrodes. We observed specific modulation of the right STN in response to anger and happiness, as opposed to neutral prosody, occurring at around 200–300ms post-onset, and later at around 850–950ms post-onset for anger and at around 3250–3350ms post-onset for happiness. Taken together with previous reports of modulated STN activity in response to emotional visual stimuli, the present results appear to confirm that the STN is involved in emotion processing irrespective of stimulus valence and sensory modality.

Early dysfunction and progressive degeneration of the subthalamic nucleus in mouse models of Huntington's disease.

The subthalamic nucleus (STN) is an element of cortico-basal ganglia-thalamo-cortical circuitry critical for action suppression. In Huntington's disease (HD) action suppression is impaired, resembling the effects of STN lesioning or inactivation. To explore this potential linkage, the STN was studied in BAC transgenic and Q175 knock-in mouse models of HD. At <2 and 6 months of age autonomous STN activity was impaired due to activation of KATP channels. STN neurons exhibited prolonged NMDA receptor-mediated synaptic currents, caused by a deficit in glutamate uptake, and elevated mitochondrial oxidant stress, which was ameliorated by NMDA receptor antagonism. STN activity was rescued by NMDA receptor antagonism or the break down of hydrogen peroxide. At 12 months of age approximately 30% of STN neurons had been lost, as in HD. Together, these data argue that dysfunction within the STN is an early feature of HD that may contribute to its expression and course.

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.

Deep brain stimulation of the subthalamic nucleus in obsessive-compulsive disorder: Neuroanatomical and pathophysiological considerations

Obsessive-compulsive disorder (OCD) is among the most disabling chronic psychiatric disorders and has a significant negative impact on multiple domains of quality of life. For patients suffering from severe refractory OCD, deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been applied. Reviewing the literature of the last years we believe that through its central position within the cortico-basal ganglia-thalamocortical circuits, the STN has a coordinating role in decision-making and action-selection mechanisms. Dysfunctional information-processing at the level of the STN is responsible for some of the core symptoms of OCD. Research confirms an electrophysiological dysfunction in the associative and limbic (non-motor) parts of the STN. Compared to Parkinson׳s disease patients, STN neurons in OCD exhibit a lower firing rate, less frequent but longer bursts, increased burst activity in the anterior ventromedial area, an asymmetrical left-sided burst distribution, and a predominant oscillatory activity in the δ-band. Moreover, there is direct evidence for the involvement of the STN in both checking behavior and OCD symptoms, which are both related to changes in electrophysiological activity in the non-motor STN. Through a combination of mechanisms, DBS of the STN seems to interrupt the disturbed information-processing, leading to a normalization of connectivity within the cortico-basal ganglia-thalamocortical circuits and consequently to a reduction in symptoms. In conclusion, based on the STN׳s strategic position within cortico-basal ganglia-thalamocortical circuits and its involvement in action-selection mechanisms that are responsible for some of the core symptoms of OCD, the STN is a mechanism-based target for DBS in OCD.

The Effects of Mechanical and Thermal Stimuli on Local Field Potentials and Single Unit Activity in Parkinson’s Disease Patients

Chronic pain is a major, debilitating symptom of Parkinson's disease (PD). Although, deep brain stimulation (DBS) has been shown to improve pain outcomes, the mechanisms underlying this phenomenon are unclear. Microelectrode recording allows us to measure both local field potentials (LFPs) and single neuronal unit activity (SUA). In this study, we examined how single unit and LFP oscillatory activity in the basal ganglia are impacted by mechanical and thermal sensory stimuli and explored their role in pain modulation. We assessed changes in LFPs and SUAs in the subthalamic nucleus (STN), globus pallidus interna (Gpi), and globus pallidus externa (Gpe) following exposure with mechanical or thermal stimuli. Sensory thresholds were determined pre-operatively using quantitative sensory testing. Based on these data, patients were exposed to innocuous and noxious mechanical, pressure, and thermal stimuli at individualized thresholds. In the STN, LFP alpha oscillatory activity and SUA increased in response to innocuous mechanical stimuli; SUA further increased in response to noxious mechanical, noxious pressure, and noxious thermal stimuli (p < 0.05). In the Gpe, LFP low betaactivity and SUA increased with noxious thermal stimuli; SUA also increased in response to innocuous thermal stimuli (p < 0.05). In the Gpi, innocuous thermal stimuli increased LFP gammaactivity; noxious pressure stimuli decreased low betaactivity; SUA increased in response to noxious thermal stimuli (p < 0.05). Our study is the first to demonstrate that mechanical and thermal stimuli alter basal ganglia LFPs and SUAs in PD. While STN SUA increases nearly uniformly to all sensory stimuli, SUA in the pallidal nuclei respond solely to thermal stimuli. Similarly, thermal stimuli yield increases in pallidal LFP activity, but not STN activity. We speculate that DBS may provide analgesia through suppression of stimuli-specific changes in basal ganglia activity, supporting a role for these nuclei in sensory and pain processing circuits.

C.01.01 - Cognitive domains affected by major depressive disorder (MDD)

Obsessive-compulsive disorder (OCD) is among the most disabling chronic psychiatric disorders and has a significant negative impact on multiple domains of quality of life. For patients suffering from severe refractory OCD, deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been applied. Reviewing the literature of the last years we believe that through its central position within the cortico-basal ganglia-thalamocortical circuits, the STN has a coordinating role in decision-making and action-selection mechanisms. Dysfunctional information-processing at the level of the STN is responsible for some of the core symptoms of OCD. Research confirms an electrophysiological dysfunction in the associative and limbic (non-motor) parts of the STN. Compared to Parkinson׳s disease patients, STN neurons in OCD exhibit a lower firing rate, less frequent but longer bursts, increased burst activity in the anterior ventromedial area, an asymmetrical left-sided burst distribution, and a predominant oscillatory activity in the δ-band. Moreover, there is direct evidence for the involvement of the STN in both checking behavior and OCD symptoms, which are both related to changes in electrophysiological activity in the non-motor STN. Through a combination of mechanisms, DBS of the STN seems to interrupt the disturbed information-processing, leading to a normalization of connectivity within the cortico-basal ganglia-thalamocortical circuits and consequently to a reduction in symptoms. In conclusion, based on the STN׳s strategic position within cortico-basal ganglia-thalamocortical circuits and its involvement in action-selection mechanisms that are responsible for some of the core symptoms of OCD, the STN is a mechanism-based target for DBS in OCD.

Probing the Role of Medication, DBS Electrode Position, and Antidromic Activation on Impulsivity Using a Computational Model of Basal Ganglia.

Everyday, we encounter situations where available choices are nearly equally rewarding (high conflict) calling for some tough decision making. Experimental recordings showed that the activity of Sub Thalamic Nucleus (STN) increases during such situations providing the extra time needed to make the right decision, teasing apart the most rewarding choice from the runner up closely trailing behind. This prolonged deliberation necessary for decision making under high conflict was absent in Parkinson's disease (PD) patients who underwent Deep Brain Stimulation (DBS) surgery of STN. In an attempt to understand the underlying cause of such adverse response, we built a 2D spiking network model (50 × 50 lattice) of Basal ganglia incorporating the key nuclei. Using the model we studied the Probabilistic learning task (PLT) in untreated, treated (L-Dopa and Dopamine Agonist) and STN-DBS PD conditions. Based on the experimental observation that dopaminergic activity is analogous to temporal difference (TD) and induces cortico-striatal plasticity, we introduced learning in the cortico-striatal weights. The results show that healthy and untreated conditions of PD model were able to more or less equally select (avoid) the rewarding (punitive) choice, a behavior that was absent in treated PD condition. The time taken to select a choice in high conflict trials was high in normal condition, which is in agreement with experimental results. The treated PD (Dopamine Agonist) patients made impulsive decisions (small reaction time) which in turn led to poor performance. The underlying cause of the observed impulsivity in DBS patients was studied in the model by (1) varying the electrode position within STN, (2) causing antidromic activation of GPe neurons. The effect of electrode position on reaction time was analyzed by studying the activity of STN neurons where, a decrease in STN neural activity was observed for certain electrode positions. We also observed that a higher antidromic activation of GPe neurons does not impact the learning ability but decreases reaction time as reported in DBS patients. These results suggest a probable role of electrode and antidromic activation in modulating the STN activity and eventually affecting the patient's performance on PLT.

Subthalamic, not striatal, activity correlates with basal ganglia downstream activity in normal and parkinsonian monkeys.

The striatum and the subthalamic nucleus (STN) constitute the input stage of the basal ganglia (BG) network and together innervate BG downstream structures using GABA and glutamate, respectively. Comparison of the neuronal activity in BG input and downstream structures reveals that subthalamic, not striatal, activity fluctuations correlate with modulations in the increase/decrease discharge balance of BG downstream neurons during temporal discounting classical condition task. After induction of parkinsonism with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), abnormal low beta (8-15 Hz) spiking and local field potential (LFP) oscillations resonate across the BG network. Nevertheless, LFP beta oscillations entrain spiking activity of STN, striatal cholinergic interneurons and BG downstream structures, but do not entrain spiking activity of striatal projection neurons. Our results highlight the pivotal role of STN divergent projections in BG physiology and pathophysiology and may explain why STN is such an effective site for invasive treatment of advanced Parkinson's disease and other BG-related disorders.

EP 63. Spectral analysis and visualization of multi-unit activity in subthalamic nucleus in Parkinson’s as a tool for automated electrophysiological classification of basal ganglia structures during deep brain stimulation procedures

Introduction In deep brain stimulation (DBS) of the subthalamic nucleus (STN) intraoperative microelectrode recordings (MER) are a well-established method for electrophysiological stereotactic target identification. Despite the main electrophysiological properties of STN are already well described ( [Cagnan et al., 2011] , [Seifried et al., 2012] ), mapping of STN rely on visual and acoustic inspection of raw recordings of MER trajectories. In this study we analyzed spectral decomposition and spike train patterns retrospectively of MER in STN-DBS to proposing a simple and reliable electrophysiological classification system. Secondly we suggest visualization techniques to present electrophysiological results in a user-friendly way. Patients and methods We analyzed MER in 7 patients with bilateral STN-DBS including 26 MER trajectories retrospectively. All recordings were carried out on multiple trajectories 10 mm prior and 4–5 mm below MR-tomographic STN target along planed DBS lead trajectory. Data was recorded intraoperative by Medtronic Leadpoint system using sharp microTargeting electrodes (FHC, USA). Offline Multi-Unit activity analysis was realized with Fieldtrip-Toolbox and Matlab, Mathworks. Statistical analysis of power spectral density, noise level and spike interstimulus interval were obtained through non-parametric student’s t-test. In purpose of visualization we integrated the stereotactic surgical plan to the electrophysiological results. Results Spectral density analysis showed a strong increase in frequency bands of 300–1000 Hz within STN borders. Spike train patterns within STN were heterogeneously and differed in firing rate and interstimulus interval to the key anatomical structures, thalamus and substantia nigra. Conclusion Through combination of spectral density analysis and spike train analysis we propose a simple and reliable MER signal classification method, which can be used for automated electrophysiological mapping of STN. Three-dimensional visualization of mapping results can provide help for decision of final DBS electrode implantation site.

A proactive task set influences how response inhibition is implemented in the basal ganglia.

Increasing a participant's ability to prepare for response inhibition is known to result in longer Go response times and is thought to engage a "top-down fronto-striatal inhibitory task set." This premise is supported by the observation of anterior striatum activation in functional magnetic resonance imaging (fMRI) analyses that focus on uncertain versus certain Go trials. It is assumed that setting up a proactive inhibitory task set also influences how participants subsequently implement stopping. To assess this assumption, we aimed to manipulate the degree of proactive inhibition in a modified stop-signal task to see how this manipulation influences activation when reacting to the Stop cue. Specifically, we tested whether there is differential activity of basal ganglia nuclei, namely the subthalamic nucleus (STN) and anterior striatum, on Stop trials when stop-signal probability was relatively low (20%) or high (40%). Successful stopping was associated with increased STN activity when Stop trials were infrequent and increased caudate head activation when Stop trials were more likely, suggesting a different implementation of reactive response inhibition by the basal ganglia for differing degrees of proactive response control. Hum Brain Mapp 37:4706-4717, 2016. © 2016 Wiley Periodicals, Inc.

Decisions Made with Less Evidence Involve Higher Levels of Corticosubthalamic Nucleus Theta Band Synchrony.

The switch between automatic action selection and more controlled forms of decision-making is a dynamic process thought to involve both cortical and subcortical structures. During sensory conflict, medial pFC oscillations in the theta band (<8 Hz) drive those of the subthalamic nucleus (STN), and this is thought to increase the threshold of evidence needed for one competing response to be selected over another. Here, we were interested in testing whether STN activity is also altered by the rate at which evidence is presented during a congruent dot motion task absent of any explicit sensory conflict. By having a series of randomly moving dots gradually transform to congruent motion at three different rates (slow, medium, fast), we were able to show that a slower rate increased the time it took participants to make a response but did not alter the total amount of evidence that was integrated before the response. Notably, this resulted in a decision being made with a lower amount of instantaneous evidence during the slow and medium trials. Consistent with the idea that medial pFC–STN activity is involved in executing cognitive control, the higher levels of ambiguity during these trials were associated with increased theta band synchrony between the cortex and the STN, with the cortical oscillations Granger-causal to those of the STN. These results further confirm the involvement of the STN in decision-making and suggest that the disruption of this network may underlie some of the unwanted cognitive deficits associated with STN deep brain stimulation.

The human subthalamic nucleus encodes the subjective value of reward and the cost of effort during decision-making.

Adaptive behaviour entails the capacity to select actions as a function of their energy cost and expected value and the disruption of this faculty is now viewed as a possible cause of the symptoms of Parkinson's disease. Indirect evidence points to the involvement of the subthalamic nucleus-the most common target for deep brain stimulation in Parkinson's disease-in cost-benefit computation. However, this putative function appears at odds with the current view that the subthalamic nucleus is important for adjusting behaviour to conflict. Here we tested these contrasting hypotheses by recording the neuronal activity of the subthalamic nucleus of patients with Parkinson's disease during an effort-based decision task. Local field potentials were recorded from the subthalamic nucleus of 12 patients with advanced Parkinson's disease (mean age 63.8 years ± 6.8; mean disease duration 9.4 years ± 2.5) both OFF and ON levodopa while they had to decide whether to engage in an effort task based on the level of effort required and the value of the reward promised in return. The data were analysed using generalized linear mixed models and cluster-based permutation methods. Behaviourally, the probability of trial acceptance increased with the reward value and decreased with the required effort level. Dopamine replacement therapy increased the rate of acceptance for efforts associated with low rewards. When recording the subthalamic nucleus activity, we found a clear neural response to both reward and effort cues in the 1-10 Hz range. In addition these responses were informative of the subjective value of reward and level of effort rather than their actual quantities, such that they were predictive of the participant's decisions. OFF levodopa, this link with acceptance was weakened. Finally, we found that these responses did not index conflict, as they did not vary as a function of the distance from indifference in the acceptance decision. These findings show that low-frequency neuronal activity in the subthalamic nucleus may encode the information required to make cost-benefit comparisons, rather than signal conflict. The link between these neural responses and behaviour was stronger under dopamine replacement therapy. Our findings are consistent with the view that Parkinson's disease symptoms may be caused by a disruption of the processes involved in balancing the value of actions with their associated effort cost.

Surprise disrupts cognition via a fronto-basal ganglia suppressive mechanism.

Surprising events markedly affect behaviour and cognition, yet the underlying mechanism is unclear. Surprise recruits a brain mechanism that globally suppresses motor activity, ostensibly via the subthalamic nucleus (STN) of the basal ganglia. Here, we tested whether this suppressive mechanism extends beyond skeletomotor suppression and also affects cognition (here, verbal working memory, WM). We recorded scalp-EEG (electrophysiology) in healthy participants and STN local field potentials in Parkinson's patients during a task in which surprise disrupted WM. For scalp-EEG, surprising events engage the same independent neural signal component that indexes action stopping in a stop-signal task. Importantly, the degree of this recruitment mediates surprise-related WM decrements. Intracranially, STN activity is also increased post surprise, especially when WM is interrupted. These results suggest that surprise interrupts cognition via the same fronto-basal ganglia mechanism that interrupts action. This motivates a new neural theory of how cognition is interrupted, and how distraction arises after surprising events.

Neural Correlates of Decision Thresholds in the Human Subthalamic Nucleus

SummaryIf humans are faced with difficult choices when making decisions, the ability to slow down responses becomes critical in order to avoid suboptimal choices. Current models of decision making assume that the subthalamic nucleus (STN) mediates this function by elevating decision thresholds, thereby requiring more evidence to be accumulated before responding [1, 2, 3, 4, 5, 6, 7, 8, 9]. However, direct electrophysiological evidence for the exact role of STN during adjustment of decision thresholds is lacking. Here, we show that trial-by-trial variations in STN low-frequency oscillatory activity predict adjustments of decision thresholds before subjects make a response. The relationship between STN activity and decision thresholds critically depends on the subjects’ level of cautiousness. While increased oscillatory activity of the STN predicts elevated decision thresholds during high levels of cautiousness, it predicts decreased decision thresholds during low levels of cautiousness. This context-dependent relationship may be mediated by increased influence of the medial prefrontal cortex (mPFC)-STN pathway on decision thresholds during high cautiousness. Subjects who exhibit a stronger increase in phase alignment of low-frequency oscillatory activity in mPFC and STN before making a response have higher decision thresholds and commit fewer erroneous responses. Together, our results demonstrate that STN low-frequency oscillatory activity and corresponding mPFC-STN coupling are involved in determining how much evidence subjects accumulate before making a decision. This finding might explain why deep-brain stimulation of the STN can impair subjects’ ability to slow down responses and can induce impulsive suboptimal decisions.

Can We Rely on Susceptibility-Weighted Imaging for Subthalamic Nucleus Identification in Deep Brain Stimulation Surgery?

Susceptibility-weighted imaging (SWI) offers significantly improved visibility of the subthalamic nucleus (STN) compared with traditional T2-weighted imaging. However, it is unknown whether the representation of the nucleus on SWI corresponds to the neurophysiological location of the STN. To determine the correlation between the intraoperative electrophysiological activity of the STN and the representation of the nucleus on different magnetic resonance imaging (MRI) sequences used for deep brain stimulation target planning. At stereotactic target depth, microelectrode recordings (MERs) of typical STN neuronal activity were mapped on 3 different preoperative MRI sequences: 1.5-T SWI, 1.5-T T2-weighted, and 3-T T2-weighted MRI. For each MRI sequence, it was determined whether the MER signal was situated inside or outside the contour of the STN. A total of 196 MER tracks in 34 patients were evaluated. In 165 tracks (84%), typical electrophysiological STN activity was measured. MER activity was situated more consistently inside hypointense STN contour representation on 1.5- and 3-T T2-weighted images compared with SWI (99% and 100% vs 79%, respectively). The 21% incongruence of electrophysiological STN activity outside the STN contour on SWI was seen almost exclusively in the anterior and lateral microelectrode channels. STN representation on SWI does not correspond to electrophysiological STN borders. SWI does not correctly display the lateral part of the STN. When aiming to target the superolateral sensorimotor part of the STN during deep brain stimulation surgery, SWI does not offer an advantage but a disadvantage compared with conventional T2. Future research is needed to determine whether these findings may also apply for high-field SWI.

Subthalamic nucleus deep brain stimulation induces impulsive action when patients with Parkinson's disease act under speed pressure.

The subthalamic nucleus (STN) is proposed to modulate response thresholds and speed–accuracy trade-offs. In situations of conflict, the STN is considered to raise response thresholds, allowing time for the accumulation of information to occur before a response is selected. Conversely, speed pressure is thought to reduce the activity of the STN and lower response thresholds, resulting in fast, errorful responses. In Parkinson’s disease (PD), subthalamic nucleus deep brain stimulation (STN-DBS) reduces the activity of the nucleus and improves motor symptoms. We predicted that the combined effects of STN stimulation and speed pressure would lower STN activity and lead to fast, errorful responses, hence resulting in impulsive action. We used the motion discrimination ‘moving-dots’ task to assess speed–accuracy trade-offs, under both speed and accuracy instructions. We assessed 12 patients with PD and bilateral STN-DBS and 12 age-matched healthy controls. Participants completed the task twice, and the patients completed it once with STN-DBS on and once with STN-DBS off, with order counterbalanced. We found that STN stimulation was associated with significantly faster reaction times but more errors under speed instructions. Application of the drift diffusion model showed that stimulation resulted in lower response thresholds when acting under speed pressure. These findings support the involvement of the STN in the modulation of speed–accuracy trade-offs and establish for the first time that speed pressure alone, even in the absence of conflict, can result in STN stimulation inducing impulsive action in PD.

Local field potential power of subthalamic nucleus in human brain is not related to scalp EEG topography dynamics in rest

Objective Subthalamic nucleus (STN) is known to have central position in basal ganglia-thalamocortical circuits. Subthalamo-cortical interactions, however, are not precisely known yet. While intracranial EEG directly explores STN, scalp EEG informs about dynamics of cortical activity, which in rest displays discrete periods of electrical stability-functional microstates. To assess subthalamo-cortical relationship, we analyzed STN and scalp EEG signals. Methods Simultaneous scalp (51–60 electrodes) and intracranial (from STNs) EEG was obtained from four Parkinson disease patients in rest. Topographic analysis was conducted to identify microstate dynamics. Correlations between scalp and STN signals were calculated. Results Time course of mean scalp power significantly correlated with that of local field potential power of both STNs (STN-LFP power) in delta, theta, alpha, beta, gamma, and 1–40 Hz frequency bands in all subjects ( r -value from 0.07 to 0.72). Microstate analysis identified typical four scalp topographies in all subjects. No correlations were found between time course of spatial correlation coefficients of template topographic maps and that of STN-LFP power in any frequency band ( r -value Conclusion While STN-LFP power was related to scalp EEG power in rest, it was not related to occurrence of scalp topographies. Key message Although maybe related to cortical activity, STN activity might not be related to occurrence of microstates.

ID 150 – STN neuron activity in patients carrying the R1441G mutation in the leucine-rich repeat kinase-2 (LRRK2) gene

Objective Mutations in the LRRK2 gene account for higher risk of suffering Parkinson’s disease (PD). To understand the basis of these differences we investigated the neuron activity in the subthalamic nucleus (STN) from patients carrying the R1441G mutation in the LRRK2 gene and without the mutation. Methods Recordings of STN neurons were obtained from intraoperative procedures performed in PD patients; with mutation in the LRRK2 gene ( n = 4, 22 neurons) and without the mutation ( n = 5, 31 neurons). All patients met the CAPSIT criteria for inclusion in the surgical program. Clinical assessment was made using the Unified Parkinson’s disease Rating Scale II, Unified Parkinson’s disease Rating Scale III, and Parkinson’s disease Questionnaire 39 scores. Results Patients with and without R1441G mutation showed equal clinical features as indicated by the used PD rating scales. Parameters of STN neuronal activity were not different among the two groups of patients neither the oscillatory activity. Conclusions Although the number of patients included in this study should be increased results suggest that the R1441G mutation does not determine clinical severity or STN activity. Key message Characteristics of STN neurons in LRRK2–R1441G PD patients are similar to idiopathic PD. Support by UFI11/32 and GV/EJ:IT747-13.

ID 39 – Oscillatory activity in the human subthalamic nucleus during spontaneous blinking

Objectives Study the involvement of the subthalamic nucleus (STN) in spontaneous blinking. Methods 8 patients with parkinson’s disease and bilateral DBS implanted in the STN were included in the study. Long segments (>20 min) of EEG and STN-LFP recordings at rest were selected both in “off” and “on” motor states. Blink artifacts in the EEG were used to select 100 segments of 4 s centered around the blink per patient and motor state. Changes in oscillatory activity were measured by means of normalized gabor transforms. Results A significant beta desynchronization (beta ERD) preceding the blink was observed in 11 of the 16 STN in the off state, and 12 out of the 16 STN in the on state. The ERD was more commonly observed in the dorsal and intermediate contact pairs (1–2, 2–3 and 5–6, 6–7). The mean beta ERD of the 8 patients was 30% in “on” and 16% in “off”. Conclusions Spontaneous blinks are preceded by a beta ERD in the STN, similar to the desynchronization observed before a voluntary movement, but of smaller amplitude. This beta ERD is best observed in the “on” motor state. Key message The STN is involved in the generation of spontaneous blinking.

Buspirone requires the intact nigrostriatal pathway to reduce the activity of the subthalamic nucleus via 5-HT1A receptors

The most effective treatment for Parkinson's disease (PD), l-DOPA, induces dyskinesia after prolonged use. We have previously shown that in 6-hydroxydopamine (6-OHDA) lesioned rats rendered dyskinetic by prolonged l-DOPA administration, lesion of the subthalamic nucleus (STN) reduces not only dyskinesias but also buspirone antidyskinetic effect. This study examined the effect of buspirone on STN neuron activity. Cell-attached recordings in parasagittal slices from naïve rats showed that whilst serotonin excited the majority of STN neurons, buspirone showed an inhibitory main effect but only in 27% of the studied cells which was prevented by the 5-HT1A receptor selective antagonist WAY-100635. Conversely, single-unit extracellular recordings were performed in vivo on STN neurons from four different groups, i.e., control, chronically treated with l-DOPA, 6-OHDA lesioned and lesioned treated with l-DOPA (dyskinetic) rats. In control animals, systemic-buspirone administration decreased the firing rate in a dose-dependent manner in every cell studied. This effect, prevented by WAY-100635, was absent in 6-OHDA lesioned rats and was not modified by prolonged l-DOPA administration. Altogether, buspirone in vivo reduces consistently the firing rate of the STN neurons through 5-HT1A receptors whereas ex vivo buspirone seems to affect only a small population of STN neurons. Furthermore, the lack of effect of buspirone in 6-OHDA lesioned rats, suggests the requirement of not only the activation of 5-HT1A receptors but also an intact nigrostriatal pathway for buspirone to inhibit the STN activity.