Subthalamic Nucleus Activity Research Articles

Subthalamic Oscillatory Activity of Reward and Loss Processing Using the Monetary Incentive Delay Task in Parkinson Disease

BackgroundThe subthalamic nucleus (STN) is an effective deep brain stimulation target for Parkinson disease (PD) and obsessive-compulsive disorder and has been implicated in reward and motivational processing. In this study, we assessed the STN and prefrontal oscillatory dynamics in the anticipation and receipt of reward and loss using a task commonly used in imaging. Materials and MethodsWe recorded intracranial left subthalamic local field potentials from deep brain stimulation electrodes and prefrontal scalp electroencephalography in 17 patients with PD while they performed a monetary incentive delay task. ResultsDuring the expectation phase, enhanced left STN delta-theta activity was observed in both reward and loss vs neutral anticipation, with greater STN delta-theta activity associated with greater motivation specifically to reward. In the consummatory outcome phase, greater left STN delta activity was associated with a rewarding vs neutral outcome, particularly with more ventral contacts along with greater delta-theta coherence with the prefrontal cortex. We highlight a differential activity in the left STN to loss vs reward anticipation, demonstrating a distinct STN high gamma activity. Patients with addiction-like behaviors show lower left STN delta-theta activity to loss vs neutral outcomes, emphasizing impaired sensitivity to negative outcomes. ConclusionsTogether, our findings highlight a role for the left STN in reward and loss processing and a potential role in addictive behaviors. These findings emphasize the cognitive-limbic function of the STN and its role as a physiologic target for neuropsychiatric disorders.

Combining Multimodal Biomarkers to Guide Deep Brain Stimulation Programming in Parkinson Disease

BackgroundDeep brain stimulation (DBS) programming of multicontact DBS leads relies on a very time-consuming manual screening procedure, and strategies to speed up this process are needed. Beta activity in subthalamic nucleus (STN) local field potentials (LFP) has been suggested as a promising marker to index optimal stimulation contacts in patients with Parkinson disease. ObjectiveIn this study, we investigate the advantage of algorithmic selection and combination of multiple resting and movement state features from STN LFPs and imaging markers to predict three relevant clinical DBS parameters (clinical efficacy, therapeutic window, side-effect threshold). Materials and MethodsSTN LFPs were recorded at rest and during voluntary movements from multicontact DBS leads in 27 hemispheres. Resting- and movement-state features from multiple frequency bands (alpha, low beta, high beta, gamma, fast gamma, high frequency oscillations [HFO]) were used to predict the clinical outcome parameters. Subanalyses included an anatomical stimulation sweet spot as an additional feature. ResultsBoth resting- and movement-state features contributed to the prediction, with resting (fast) gamma activity, resting/movement-modulated beta activity, and movement-modulated HFO being most predictive. With the proposed algorithm, the best stimulation contact for the three clinical outcome parameters can be identified with a probability of almost 90% after considering half of the DBS lead contacts, and it outperforms the use of beta activity as single marker. The combination of electrophysiological and imaging markers can further improve the prediction. ConclusionLFP-guided DBS programming based on algorithmic selection and combination of multiple electrophysiological and imaging markers can be an efficient approach to improve the clinical routine and outcome of DBS patients.

Dissociation of impulsive traits by subthalamic metabotropic glutamate receptor 4.

Behavioral strategies require gating of premature responses to optimize outcomes. Several brain areas control impulsive actions, but the neuronal basis of natural variation in impulsivity between individuals remains largely unknown. Here, by combining a Go/No-Go behavioral assay with resting-state (rs) functional MRI in mice, we identified the subthalamic nucleus (STN), a known gate for motor control in the basal ganglia, as a major hotspot for trait impulsivity. In vivo recorded STN neural activity encoded impulsive action as a separable state from basic motor control, characterized by decoupled STN/substantia nigra pars reticulata (SNr) mesoscale networks. Optogenetic modulation of STN activity bidirectionally controlled impulsive behavior. Pharmacological and genetic manipulations showed that these impulsive actions are modulated by metabotropic glutamate receptor 4 (mGlu4) function in STN and its coupling to SNr in a behavioral trait-dependent manner, and independently of general motor function. In conclusion, STN circuitry multiplexes motor control and trait impulsivity, which are molecularly dissociated by mGlu4. This provides a potential mechanism for the genetic modulation of impulsive behavior, a clinically relevant predictor for developing psychiatric disorders associated with impulsivity.

Locus coeruleus integrity correlates with inhibitory functions of the fronto-subthalamic ‘hyperdirect’ pathway in Parkinson’s disease

A long-running debate concerns whether dopamine or noradrenaline deficiency drives response disinhibition in Parkinson’s disease (PD). This study aimed to investigate whether damage to the locus coeruleus (LC) or substantia nigra (SN) might impact inhibitory functions of the fronto-subthalamic hyperdirect or fronto-striatal indirect pathway. Patients with PD (n = 29, 13 women) and matched healthy controls (n = 29, 15 women) participated in this cross-sectional study. LC and SN integrity was assessed using neuromelanin-sensitive MRI. Response inhibition was measured using fMRI with a stop-signal task. In healthy controls, LC (but not SN) integrity correlated with the stopping-related activity of the right inferior frontal gyrus (IFG) and right subthalamic nucleus (STN), which further correlated with stop-signal reaction time (SSRT). PD patients showed reduced LC integrity, longer SSRT, and lower stopping-related activity over the right IFG, pre-supplementary motor area, and right caudate nucleus than healthy controls. In PD patients, the relationship between SSRT and the fronto-subthalamic pathway was preserved. However, LC integrity no longer correlated with the stopping-related right IFG or right STN activity. No contribution of SN integrity was found during stopping. In conclusion, LC (but not SN) might modulate inhibitory functions of the right IFG-STN pathway. Damage to the LC might impact the right IFG-STN pathway during stopping, leading to response disinhibition in PD.

Double-blind cross-over pilot trial protocol to evaluate the safety and preliminary efficacy of long-term adaptive deep brain stimulation in patients with Parkinson’s disease

IntroductionAfter several years of brain-sensing technology development and proof-of-concept studies, adaptive deep brain stimulation (aDBS) is ready to better treat Parkinson’s disease (PD) using aDBS-capable implantable pulse generators (IPGs). New...

Theta Oscillations at Subthalamic Region Predicts Hypomania State After Deep Brain Stimulation in Parkinson's Disease.

Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective treatment for the motor impairments of patients with advanced Parkinson's disease. However, mood or behavioral changes, such as mania, hypomania, and impulsive disorders, can occur postoperatively. It has been suggested that these symptoms are associated with the stimulation of the limbic subregion of the STN. Electrophysiological studies demonstrate that the low-frequency activities in ventral STN are modulated during emotional processing. In this study, we report 22 patients with Parkinson's disease who underwent STN DBS for treatment of motor impairment and presented stimulation-induced mood elevation during initial postoperative programming. The contact at which a euphoric state was elicited by stimulation was termed as the hypomania-inducing contact (HIC) and was further correlated with intraoperative local field potential recorded during the descending of DBS electrodes. The power of four frequency bands, namely, θ (4–7 Hz), α (7–10 Hz), β (13–35 Hz), and γ (40–60 Hz), were determined by a non-linear variation of the spectrogram using the concentration of frequency of time (conceFT). The depth of maximum θ power is located approximately 2 mm below HIC on average and has significant correlation with the location of contacts (r = 0.676, p < 0.001), even after partializing the effect of α and β, respectively (r = 0.474, p = 0.022; r = 0.461, p = 0.027). The occurrence of HIC was not associated with patient-specific characteristics such as age, gender, disease duration, motor or non-motor symptoms before the operation, or improvement after stimulation. Taken together, these data suggest that the location of maximum θ power is associated with the stimulation-induced hypomania and the prediction of θ power is frequency specific. Our results provide further information to refine targeting intraoperatively and select stimulation contacts in programming.

Simultaneously recorded subthalamic and cortical LFPs reveal different lexicality effects during reading aloud.

Many language functions are traditionally assigned to cortical brain areas, leaving the contributions of subcortical structures to language processing largely unspecified. The present study examines a potential role of the subthalamic nucleus (STN) in lexical processing, specifically, reading aloud of words (e.g., 'fate') and pseudowords (e.g., 'fape'). We recorded local field potentials simultaneously from the STN and the cortex (precentral, postcentral, and superior temporal gyri) of 13 people with Parkinson's disease undergoing awake deep brain stimulation and compared STN's lexicality-related neural activity with that of the cortex. Both STN and cortical activity demonstrated significant task-related modulations, but the lexicality effects were different in the two brain structures. In the STN, an increase in gamma band activity (31-70 Hz) was present in pseudoword trials compared to word trials during subjects' spoken response. In the cortex, a greater decrease in beta band activity (12-30 Hz) was observed for pseudowords in the precentral gyrus. Additionally, 11 individual cortical sites showed lexicality effects with varying temporal and topographic characteristics in the alpha and beta frequency bands. These findings suggest that the STN and the sampled cortical regions are involved differently in the processing of lexical distinctions.

Impaired Timing of Speech-Related Neurons in the Subthalamic Nucleus of Parkinson Disease Patients Suffering Speech Disorders.

Our previous study found degradation to subthalamic neuronal encoding of speech features in Parkinson disease (PD) patients suffering from speech disorders. To find how timing of speech-related neuronal firing changes in PD patients with speech disorders compared to PD patients without speech disorders. During the implantation of deep brain stimulator (DBS), we recorded the activity of single neurons in the subthalamic nucleus (STN) of 18 neurosurgical patients with PD while they articulated, listened to, or imagined articulation of 5 vowel sounds, each following a beep. We compared subthalamic activity of PD patients with (n=10) vs without speech disorders. In this comparison, patients with speech disorders had longer reaction times and shorter lengths of articulation. Their speech-related neuronal activity preceding speech onset (planning) was delayed relative to the beep, but the time between this activity and the emission of speech sound was similar. Notwithstanding, speech-related neuronal activity following the onset of speech (feedback) was delayed when computed relative to the onset. Only in these patients was the time lag of planning neurons significantly correlated with the reaction time. Neuronal activity in patients with speech disorders was delayed during imagined articulation of vowel sounds but earlier during speech perception. Our findings indicate that longer reaction times in patients with speech disorders are due to STN or earlier activity of the speech control network. This is a first step in locating the source(s) of PD delays within this network and is therefore of utmost importance for future treatment of speech disorders.

Chemogenetic modulation reveals distinct roles of the subthalamic nucleus and its afferents in the regulation of locomotor sensitization to amphetamine in rats.

The subthalamic nucleus (STN) is a key node in cortico-basal-ganglia thalamic circuits, guiding behavioral output through its position as an excitatory relay of the striatal indirect pathway and its direct connections with the cortex. There have been conflicting results regarding the role of the STN in addiction-related behavior to psychostimulants, and little is known with respect to the role of STN afferents. To address this, we used viral vectors to express DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) in the STN of rats in order to bidirectionally manipulate STN activity during the induction of amphetamine sensitization. In addition, we used a Cre-recombinase dependent Gi/o-coupled DREADD approach to transiently inhibit afferents from ventral pallidum (a subcomponent of the striatal indirect pathway) or the prelimbic cortex (a subcomponent of the cortico-STN hyperdirect pathway). Despite inducing mild hyperactivity in non-drug controls, stimulation of STN neurons with Gq-DREADDs blocked the development and persistence of amphetamine sensitization as well as conditioned responding. In contrast, inhibition of STN neurons with Gi/o-DREADDs enhanced the induction of sensitization without altering its persistence or conditioned responding. Chemogenetic inhibition of afferents from ventral pallidum had no effect on amphetamine sensitization but blocked conditioned responding whereas chemogenetic inhibition of afferents from prelimbic cortex attenuated the persistence of sensitization as well as conditioned responding. These results suggest the STN and its afferents play complex roles in the regulation of amphetamine sensitization and highlight the need for further characterization of how integration of inputs within STN guide behavior.

Distinct population code for movement kinematics and changes of ongoing movements in human subthalamic nucleus.

The subthalamic nucleus (STN) is theorized to globally suppress movement through connections with downstream basal ganglia structures. Current theories are supported by increased STN activity when subjects withhold an uninitiated action plan, but a critical test of these theories requires studying STN responses when an ongoing action is replaced with an alternative. We perform this test in subjects with Parkinson's disease using an extended reaching task where the movement trajectory changes mid-action. We show that STN activity decreases during action switches, contrary to prevalent theories. Furthermore, beta oscillations in the STN local field potential, which are associated with movement inhibition, do not show increased power or spiking entrainment during switches. We report an inhomogeneous population neural code in STN, with one sub-population encoding movement kinematics and direction and another encoding unexpected action switches. We suggest an elaborate neural code in STN that contributes to planning actions and changing the plans.

Articulatory Gain Predicts Motor Cortex and Subthalamic Nucleus Activity During Speech.

Speaking precisely is important for effective verbal communication, and articulatory gain is one component of speech motor control that contributes to achieving this goal. Given that the basal ganglia have been proposed to regulate the speed and size of limb movement, that is, movement gain, we explored the basal ganglia contribution to articulatory gain, through local field potentials (LFP) recorded simultaneously from the subthalamic nucleus (STN), precentral gyrus, and postcentral gyrus. During STN deep brain stimulation implantation for Parkinson's disease, participants read aloud consonant-vowel-consonant syllables. Articulatory gain was indirectly assessed using the F2 Ratio, an acoustic measurement of the second formant frequency of/i/vowels divided by/u/vowels. Mixed effects models demonstrated that the F2 Ratio correlated with alpha and theta activity in the precentral gyrus and STN. No correlations were observed for the postcentral gyrus. Functional connectivity analysis revealed that higher phase locking values for beta activity between the STN and precentral gyrus were correlated with lower F2 Ratios, suggesting that higher beta synchrony impairs articulatory precision. Effects were not related to disease severity. These data suggest that articulatory gain is encoded within the basal ganglia-cortical loop.

Neural signatures of hyperdirect pathway activity in Parkinson\u2019s disease

Parkinson’s disease (PD) is characterised by the emergence of beta frequency oscillatory synchronisation across the cortico-basal-ganglia circuit. The relationship between the anatomy of this circuit and oscillatory synchronisation within it remains unclear. We address this by combining recordings from human subthalamic nucleus (STN) and internal globus pallidus (GPi) with magnetoencephalography, tractography and computational modelling. Coherence between supplementary motor area and STN within the high (21–30 Hz) but not low (13-21 Hz) beta frequency range correlated with ‘hyperdirect pathway’ fibre densities between these structures. Furthermore, supplementary motor area activity drove STN activity selectively at high beta frequencies suggesting that high beta frequencies propagate from the cortex to the basal ganglia via the hyperdirect pathway. Computational modelling revealed that exaggerated high beta hyperdirect pathway activity can provoke the generation of widespread pathological synchrony at lower beta frequencies. These findings suggest a spectral signature and a pathophysiological role for the hyperdirect pathway in PD.

HEMICHOREA-HEMIBALLISMUS INDUCED BY NON-KETOTIC HYPERGLYCEMIA: CASE REPORT

Non-ketotic hyperglycemia with hemichorea-Hemiballismus (HGSC) is a rare complication of a non-equilibrated diabetic disease characterized by a continuous rapid, non-rhythmic, involuntary unilateral movement of the extremities, caused in most cases by decreased activity of the contralateral subthalamic nucleus of the basal ganglia. It may reveal undiagnosed diabetes. We describe here the case of an 84-year-old Moroccan woman followed for type 2 diabetes mellitus under treatment, who presented with abnormal movements of the right half-body. Laboratory tests showed higher blood glucose levels, urinary ketones were negative, brain CT without injection showed high density in the basal ganglia on the left side.

Optimized Propofol Anesthesia Increases Power of Subthalamic Neuronal Activity in Patients with Parkinson's Disease Undergoing Deep Brain Stimulation.

IntroductionPropofol is a general anesthetic option for deep brain stimulation (DBS) of the subthalamic nucleus (STN) of patients with Parkinson's disease (PD). However, its effects on STN activity and neuropsychological outcomes are controversial. The optimal propofol anesthesia for asleep DBS is unknown. This study investigated the safety and effectiveness of an optimized propofol anesthesia regimen in asleep DBS.MethodsThis retrospective study enrolled 68 PD patients undergoing bilateral STN-DBS surgery. All patients received local scalp anesthesia, with (asleep group, n = 35) or without (awake group, n = 33) propofol-remifentanil general anesthesia by target-controlled infusion under electroencephalogram monitoring. The primary outcome was subthalamic neuronal spiking characterization during microelectrode recording. The secondary outcomes were clinical outcomes including motor, cognition, mind, sleep, and quality of life at 6 months.ResultsSignificantly increased delta and theta power were obtained under propofol anesthesia (awake vs. asleep group, mean ± standard deviation; delta: 31.97 ± 9.87 vs. 39.77 ± 10.56, p < 0.01; theta: 21.09 ± 5.55 vs. 24.82 ± 6.63, p = 0.01). After excluding the influence of confounding factors of age and preoperative motor scores, there was a statistically significant influence on the delta, theta, and alpha power of STN neuronal activity under different anesthesia regimens (delta: β = 2.64, p < 0.01; theta: β = 2.11, p < 0.01; alpha: β = 1.42, p = 0.01). There were no differences in modified burst index, firing rate, tract numbers of microelectrode recording, and other clinical outcomes between the two groups.ConclusionOptimized propofol anesthesia enhanced the delta, theta, and alpha power in STN compared with the awake technique and likely contributed to target recognition under propofol anesthesia. These results demonstrate that propofol is suitable, but needs to be optimized, for asleep STN-DBS.Trial RegistrationChinese Clinical Trial Registry Identification number: ChiCTR2100045942. Registered 29 April 2021–Retrospectively registeredSupplementary InformationThe online version contains supplementary material available at 10.1007/s40120-021-00259-y.

Machine learning-based personalized subthalamic biomarkers predict ON-OFF levodopa states in Parkinson patients

Objective. Adaptive deep brain stimulation (aDBS) based on subthalamic nucleus (STN) electrophysiology has recently been proposed to improve clinical outcomes of DBS for Parkinson’s disease (PD) patients. Many current models for aDBS are based on one or two electrophysiological features of STN activity, such as beta or gamma activity. Although these models have shown interesting results, we hypothesized that an aDBS model that includes many STN activity parameters will yield better clinical results. The objective of this study was to investigate the most appropriate STN neurophysiological biomarkers, detectable over long periods of time, that can predict OFF and ON levodopa states in PD patients. Approach. Long-term local field potentials (LFPs) were recorded from eight STNs (four PD patients) during 92 recording sessions (44 OFF and 48 ON levodopa states), over a period of 3–12 months. Electrophysiological analysis included the power of frequency bands, band power ratio and burst features. A total of 140 engineered features was extracted for 20 040 epochs (each epoch lasting 5 s). Based on these engineered features, machine learning (ML) models classified LFPs as OFF vs ON levodopa states. Main results. Beta and gamma band activity alone poorly predicts OFF vs ON levodopa states, with an accuracy of 0.66 and 0.64, respectively. Group ML analysis slightly improved prediction rates, but personalized ML analysis, based on individualized engineered electrophysiological features, were markedly better, predicting OFF vs ON levodopa states with an accuracy of 0.8 for support vector machine learning models. Significance. We showed that individual patients have unique sets of STN neurophysiological biomarkers that can be detected over long periods of time. ML models revealed that personally classified engineered features most accurately predict OFF vs ON levodopa states. Future development of aDBS for PD patients might include personalized ML algorithms.

The effect of 5-HT1A receptor agonists on the entopeduncular nucleus is modified in 6-hydroxydopamine-lesioned rats.

Background and Purpose l‐DOPA prolonged treatment leads to disabling motor complications as dyskinesia that could be decreased by drugs acting on 5‐HT1A receptors. Since the internal segment of the globus pallidus, homologous to the entopeduncular nucleus in rodents, seems to be involved in the etiopathology of l‐DOPA‐induced dyskinesia, we investigated whether the entopeduncular nucleus is modulated by the 5‐HT1A receptor partial and full agonists, buspirone, and 8‐hydroxy‐2‐(di‐n‐propylamino)‐tetralin (8‐OH‐DPAT) in control and 6‐hydroxydopamine (6‐OHDA)‐lesioned rats with or without long‐term l‐DOPA treatment.Experimental ApproachExtracellular single‐unit electrocorticogram and local field potential recordings under anaesthesia, immunostaining assays and optogenetic manipulation coupled to electrophysiological recordings were performed.Key ResultsSystemic buspirone reduced the entopeduncular nucleus firing rate in the sham animals and burst activity in the 6‐OHDA‐lesioned rats (with or without l‐DOPA treatment), while local administration reduced entopeduncular nucleus activity in all the groups, regardless of DA integrity. Systemic 8‐OH‐DPAT also induced inhibitory effects only in the sham animals. Effects triggered by buspirone and 8‐OH‐DPAT were reversed by the 5‐HT1A receptor antagonist, WAY‐100635. Neither buspirone nor 8‐OH‐DPAT modified the low‐frequency oscillatory activity in the entopeduncular nucleus or its synchronization with the motor cortex. Buspirone did not alter the response induced by subthalamic nucleus opto‐stimulation in the entopeduncular nucleus.Conclusion and ImplicationsSystemic 5‐HT1A receptor activation elicits different effects on the electrophysiological properties of the entopeduncular nucleus depending on the integrity of the nigrostriatal pathway and it does not alter the relationship between subthalamic nucleus and entopeduncular nucleus neuron activity.

Effects of dexmedetomidine on subthalamic local field potentials in Parkinson's disease

BackgroundDexmedetomidine is frequently used for sedation during deep brain stimulator implantation in patients with Parkinson's disease, but its effect on subthalamic nucleus activity is not well known. The aim of this study was to quantify the effect of increasing doses of dexmedetomidine in this population. MethodsControlled clinical trial assessing changes in subthalamic activity with increasing doses of dexmedetomidine (from 0.2 to 0.6 μg kg−1 h−1) in a non-operating theatre setting. We recorded local field potentials in 12 patients with Parkinson's disease with bilateral deep brain stimulators (24 nuclei) and compared basal activity in the nuclei of each patient and activity recorded with different doses. Plasma levels of dexmedetomidine were obtained and correlated with the dose administered. ResultsWith dexmedetomidine infusion, patients became clinically sedated, and at higher doses (0.5–0.6 μg kg−1 h−1) a significant decrease in the characteristic Parkinsonian subthalamic activity was observed (P<0.05 in beta activity). All subjects awoke to external stimulus over a median of 1 (range: 0–9) min, showing full restoration of subthalamic activity. Dexmedetomidine dose administered and plasma levels showed a positive correlation (repeated measures correlation coefficient=0.504; P<0.001). ConclusionsPatients needing some degree of sedation throughout subthalamic deep brain stimulator implantation for Parkinson's disease can probably receive dexmedetomidine up to 0.6 μg kg−1 h−1 without significant alteration of their characteristic subthalamic activity. If patients achieve a ‘sedated’ state, subthalamic activity decreases, but they can be easily awakened with a non-pharmacological external stimulus and recover baseline subthalamic activity patterns in less than 10 min. Clinical trial registrationEudraCT 2016-002680-34; NCT-02982512.

The neurobiology of environmentally induced stereotypic behaviours in captive animals: assessing the basal ganglia pathways and cortico-striatal-thalamo-cortical circuitry hypotheses

Abstract The neurobiology of environmentally induced stereotypic behaviours (SBs) (e.g., pacing in zoo carnivores, crib-biting in horses, tail chasing in dogs) is hypothesized to involve altered functioning within the basal ganglia (‘Basal Ganglia (BG) Pathways Hypotheses’) and/or between the basal ganglia and cortex (‘Cortico-Striatal-Thalamo-Cortical (CSTC) Circuits Hypotheses’). We review four decades of relevant studies, critically assessing support for both hypotheses. Currently no BG Pathways or CSTC Circuits hypothesis is fully supported. While some results are partially consistent with some hypotheses (decreased subthalamic nucleus activity in deer mice and C58 mice); others (nucleus accumbens activity in mink and C57 mice) seem to reflect individual differences in SB, but not environmental effects. Yet others can be tentatively rejected: neither elevated striatal dopamine nor the cortico-striatal connection of the sensorimotor circuit seem to be involved for most species studied to date. Further research is now important for understanding the impact of captivity on animals’ functioning.

An intra-operative feature-based classification of microelectrode recordings to support the subthalamic nucleus functional identification during deep brain stimulation surgery

Objective. The subthalamic nucleus (STN) is the most selected target for the placement of the Deep Brain Stimulation (DBS) electrode to treat Parkinson’s disease. Its identification is a delicate and challenging task which is based on the interpretation of the STN functional activity acquired through microelectrode recordings (MERs). Aim of this work is to explore the potentiality of a set of 25 features to build a classification model for the discrimination of MER signals belonging to the STN. Approach. We explored the use of different sets of spike-dependent and spike-independent features in combination with an ensemble trees classification algorithm on a dataset composed of 13 patients receiving bilateral DBS. We compared results from six subsets of features and two dataset conditions (with and without standardization) using performance metrics on a leave-one-patient-out validation schema. Main results. We obtained statistically better results (i.e. higher accuracy p-value = 0.003) on the RAW dataset than on the standardized one, where the selection of seven features using a minimum redundancy maximum relevance algorithm provided a mean accuracy of 94.1%, comparable with the use of the full set of features. In the same conditions, the spike-dependent features provided the lowest accuracy (86.8%), while a power density-based index was shown to be a good indicator of STN activity (92.3%). Significance. Results suggest that a small and simple set of features can be used for an efficient classification of MERs to implement an intraoperative support for clinical decision during DBS surgery.

Resting-State Phase-Amplitude Coupling Between the Human Subthalamic Nucleus and Cortical Activity: A Simultaneous Intracranial and Scalp EEG Study.

It has been suggested that slow oscillations in the subthalamic nucleus (STN) reflect top-down inputs from the medial prefrontal cortex, thus implementing behavior control. It is unclear, however, whether the STN oscillations are related to cortical activity in a bottom-up manner. To assess resting-state subcortico-cortical interactions, we recorded simultaneous scalp electroencephalographic activity and local field potentials in the STN (LFP-STN) in 11 patients with Parkinson's disease implanted with deep brain stimulation electrodes in the on-medication state during rest. We assessed the cross-structural phase-amplitude coupling (PAC) between the STN and cortical activity within a wide frequency range of 1 to 100Hz. The PAC was dominant between the δ/θ STN phase and β/γ cortical amplitude in most investigated scalp regions and between the δ cortical phase and θ/α STN amplitude in the frontal and temporal regions. The cross-frequency linkage between the slow oscillations of the LFP-STN activity and the amplitude of the scalp-recorded cortical activity at rest was demonstrated, and similar involvement of the left and right STNs in the coupling was observed. Our results suggest that the STN plays a role in both bottom-up and top-down processes within the subcortico-cortical circuitries of the human brain during the resting state. A relative left-right symmetry in the STN-cortex functional linkage was suggested. Practical treatment studies would be necessary to assess whether unilateral stimulation of the STN might be sufficient for treatment of Parkinson's disease.