Brain tissue energy dependence of CaM kinase IV cascade activation during hypoxia in the cerebral cortex of newborn piglets

Using an anti-cue keypress task, we examined executive control in Parkinson's disease (PD) patients treated with deep brain stimulation (DBS) of the subthalamic nucleus (STN) and dopaminergic medication. Across sessions, we varied stimulation (on, off) and dopaminergic medication (on, off). Reaction time (RT) results of the PD patients and their age-matched controls showed a consistent pattern of RT costs and benefits generated by anti-cues with short and long preparation intervals, respectively. This pattern was evident in all sessions, except when DBS stimulation and medication were off. In this condition PD patients showed no RT benefits. These findings are discussed in terms of an executive control process that suppresses the automatic but inappropriate response activation generated by anti-cues. In PD this mechanism is severely compromised but it can be remediated by dopaminergic medication and DBS, suggesting an essential role of the basal ganglia in the selection and suppression of competing responses.     

The impact of low-frequency stimulation of subthalamic region on self-generated isometric contraction in patients with Parkinson’s disease

Growing evidence suggests that spontaneous oscillatory low-frequency synchronization in the subthalamic nuclei (STN) may modulate motor performance in patients with Parkinson’s disease (PD). To explore this in more detail, 15 PD patients chronically implanted with deep brain stimulation (DBS) electrodes in both STN were stimulated bilaterally at 5, 10, 20, 50 and 130 Hz and the effects of the DBS on self-initiated isometric elbow flexion (FLEX) and finger pinch (PINCH) were compared to performance without DBS. Baseline performance was very much impaired. Peak force was significantly greater during 130 and 10 Hz stimulation when compared to no stimulation in both tasks. Cumulative sums of the changes in mean rising force and peak force in the two tasks upon stimulation at 10 and 20 Hz demonstrated that patients improved their performance on stimulation, except for those with the best performance off stimulation who deteriorated with stimulation at 20 Hz. Thus, no effect was detected with 20 Hz stimulation at the group level. The current study highlights the need to consider the baseline performance of a subject in a given task when determining the effects of low-frequency STN stimulation in PD patients. It also demonstrates that stimulation at 10 Hz can improve motor function in subjects with poor baseline function.     

Effects of pallidal deep brain stimulation and levodopa treatment on reaction-time performance in Parkinson’s disease

Basal ganglia-thalamocortical circuits play an important role in movement preparation and execution. Tracer, single-cell, and lesion studies in monkeys suggest the existence of topologically segregated motor and nonmotor basal ganglia cortical circuits. In this study we used deep brain stimulation (DBS) of the posteroventrolateral globus pallidus internus (GPi) in patients with Parkinson's disease to elucidate the function of the GPi in human sensorimotor behavior. This question was investigated by comparing the influence of DBS on patients' performance in various reaction-time tasks that differed with respect to cognitive but not motor requirements. As a main result, DBS improved performance on the different tasks independently of the complexity of the involved cognitive processing functions. Furthermore, the observed effects did not depend on the modality of the processed information. These results suggest that the functional state of the posteroventrolateral GPi selectively affects the motor stage in simple sensorimotor acts, because this stage was the only stage involved in all investigated tasks. In addition to DBS, we manipulated the levodopa medication state of the PD patients. In contrast to DBS, levodopa effects on reaction times were less consistent. Levodopa improved reaction times in choice reaction tasks significantly, while affecting reaction times in a simple reaction task to a lesser extent. Error analysis revealed that the medication-dependent reaction-time improvement in the choice reaction tasks was accompanied by an increase in errors, suggesting a shift of the speed-accuracy criteria of the patients. A similar pattern of results was not observed for the DBS effects. Taken together, our data are in agreement with recent findings in monkeys that indicate a topological organization of the GPi in which motor functions are localized in posterolateral regions apart from cognitive regions. Furthermore, our data show a way to uncover the subcortical-cortical circuitry serving human sensorimotor behavior.     

长时程深部脑刺激外侧苍白球对转基因Huntington病大鼠认知和运动的影响(英文)

我们研究了深部脑刺激(deep brain stimulation, DBS)对转基因Huntington病大鼠认知能力和运动功能的影响。实验结果表明:电极植入手术能改善Huntington病大鼠的认知能力,例如:在选择反应时间实验(choice reaction time task,CRT task)中,反应准确率增加,偏倚率减少。但对不同基因型大鼠,改善程度相同。在对大鼠外侧苍白球部(GPe)进行长时间深部脑刺激后,反应准确率增加,不同基因型大鼠的增加幅度有所不同。另外,深部脑刺激后, CRT实验中的运动时间和反应时间并没有变化。但是纯合子大鼠的舞蹈样运动明显改善。本研究结果表明深部脑刺激转基因Huntington病大鼠的GPe能明显改善其认知能力和运动功能,这预示着DBS在Huntington病的治疗中将有很大的应用前景。     

Early,untreated Parkinson's disease patients show reaction time variability

While Parkinson's disease (PD) is associated with motor slowing, less attention has been paid to variability in performance on motor and cognitive tasks. To examine reaction time latencies and intraindividual variability in untreated patients with PD compared to healthy controls. Twenty-nine (19 men/10 women) patients with untreated PD and 16 controls (8 men/8 women) were examined using measures of simple reaction time (SRT) and choice reaction time (CRT) in addition to cognitive measures of executive function (Trail Making Test; adaptive digit ordering). Latencies and intraindividual variability were compared between groups. Partial correlation coefficients, adjusting for age, sex and education were used to examine the relationship between RT measures and motor or cognitive measures. Patients and controls did not differ with respect to age or sex distribution. Education and cognitive status differed between groups, but no subject was demented or clinically depressed. After adjusting for age, sex and education, significant group differences were found in latencies (2-choice RT and 8-choice RT) and intraindividual variability scores (all CRT conditions). Latencies did not differ significantly after adjusting for finger tapping rate. In the PD group neither the motor nor the executive measures correlated significantly with any of the reaction time measures. We conclude that CRT intraindividual variability and latencies are increased in untreated PD.     

Bilateral stimulation of the subthalamic nucleus has differential effects on reactive and proactive inhibition and conflict-induced slowing in Parkinson’s disease

It has been proposed that the subthalamic nucleus (STN) mediates response inhibition and conflict resolution through the fronto-basal ganglia pathways. Our aim was to compare the effects of deep brain stimulation (DBS) of the STN on reactive and proactive inhibition and conflict resolution in Parkinson’s disease using a single task. We used the conditional Stop signal reaction time task that provides the Stop signal reaction time (SSRT) as a measure of reactive inhibition, the response delay effect (RDE) as a measure of proactive inhibition and conflict-induced slowing (CIS) as a measure of conflict resolution. DBS of the STN significantly prolonged SSRT relative to stimulation off. However, while the RDE measure of proactive inhibition was not significantly altered by DBS of the STN, relative to healthy controls, RDE was significantly lower with DBS off but not DBS on. DBS of the STN did not alter the mean CIS but produced a significant differential effect on the slowest and fastest RTs on conflict trials, further prolonging the slowest RTs on the conflict trials relative to DBS off and to controls. These results are the first demonstration, using a single task in the same patient sample, that DBS of the STN produces differential effects on reactive and proactive inhibition and on conflict resolution, suggesting that these effects are likely to be mediated through the impact of STN stimulation on different fronto-basal ganglia pathways: hyperdirect, direct and indirect.     

Neuropsychological functioning following bilateral subthalamic nucleus stimulation in Parkinson's disease.

The cognitive effects of subthalamic nucleus (STN) stimulation in Parkinson's disease (PD) have been examined. However, there are no reported studies that evaluate, by incorporating a disease control group, whether neuropsychological performance in surgical patients changes beyond the variability of the assessment measures. To examine this issue, 17 PD patients were tested before and after bilateral STN stimulator implantation, both on and off stimulation. Eleven matched PD controls were administered the same repeatable neuropsychological test battery twice. Relative to changes seen in the controls, the surgery for electrode placement mildly adversely affected attention and language functions. STN stimulation, per se, had little effect on cognition. The STN DBS procedure as a whole resulted in a mild decline in delayed verbal recall and language functions. There were no surgery, stimulation, or procedure effects on depression scale scores. In contrast to these group findings, one DBS patient demonstrated significant cognitive decline following surgery.     

Gait and postural instability in Parkinson's disease treated with deep brain stimulation of the subthalamic nucleus

In late stage Parkinson's disease (PD), medical treatment may not control the symptoms adequately, and the patient may become eligible for bilateral high frequency deep brain stimulation (DBS) in the subthalamic nucleus (STN). The effect of STN DBS on gait and postural instability is not always as predictable as the effect on clinical symptoms tremor, rigidity and bradykinesia. This may relate to the type of gait disorder or the stimulating electrode localization in the STN. We sought to evaluate the effect of STN DBS on gait performance during overground walking and gait initiation--assessed with 3D optokinetic movement analyses--and to compare the DBS effect with stimulation site localized on peri-operative MRI. The stimulation sites were grouped according to STN borders visualised on pre-operative MRI, and the active stimulation site was compared with clinical improvement and gait parameters. STN DBS is associated with improved movement amplitude while movement duration may be unaffected by both disease and stimulation. This may imply an improvement primarily on hypokinesia including gait hypokinesia.     

Single pulse stimulation of the human subthalamic nucleus facilitates the motor cortex at short intervals

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson's disease (PD). The mechanism is poorly understood. High-frequency STN DBS has been reported to affect motor cortex excitability in a complex way, but the timing between STN stimuli and changes in motor cortical (M1) excitability has not been investigated. We examined the time course of changes in motor cortical excitability following single pulse STN DBS. We studied 14 PD patients with implanted DBS electrodes in the STN, 2 patients with electrodes in internal globus pallidus (GPi), and 1 patient with an electrode in the sensory thalamus. Transcranial magnetic stimulation (TMS) was delivered to the M1 ipsilateral to the DBS with induced currents either in the anterior-posterior direction in the brain to evoke indirect (I) waves or in the lateral-medial direction to activate corticospinal axons directly. Single pulse stimulation through the DBS contacts preceded the TMS by 0-10 ms. Surface EMG was recorded from the contralateral first dorsal interosseous muscle. Three milliseconds after STN stimulation, the motor evoked potential (MEP) amplitudes produced by anterior-posterior current were significantly larger than control responses, while the responses to lateral-medial currents were unchanged. Similar facilitation also occurred after GPi stimulation, but not with thalamic stimulation. Single pulse STN stimulation facilitates the M1 at short latencies. The possible mechanisms include antidromic excitation of the cortico-STN fibers or transmission through the basal ganglia-thalamocortical pathway.     

The functional role of the subthalamic nucleus in cognitive and limbic circuits

Once it was believed that the subthalamic nucleus (STN) was no more than a relay station serving as a “gate” for ascending basal ganglia-thalamocortical circuits. Nowadays, the STN is considered to be one of the main regulators of motor function related to the basal ganglia. The role of the STN in the regulation of associative and limbic functions related to the basal ganglia has generally received little attention. In the present review, the functional role of the STN in the control of cortico-basal ganglia-thalamocortical associative and limbic circuits is discussed. In the past 20 years the concepts about the functional role of the STN have changed dramatically: from being an inhibitory nucleus to a potent excitatory nucleus, and from being involved in hyperkinesias to hypokinesias. However, it has been demonstrated only recently, mainly by reports on the behavioral (side-) effects of STN deep brain stimulation (DBS), which is a popular surgical technique in the treatment of patients suffering from advanced Parkinson Disease (PD), that the STN is clinically involved in associative and limbic functions. These findings were confirmed by results from animal studies. Experimental studies applying STN DBS or STN lesions to investigate the neuronal mechanisms involved in these procedures found profound effects on cognitive and motivational parameters. The anatomical, electrophysiological and behavioral data presented in this review point towards a potent regulatory function of the STN in the processing of associative and limbic information towards cortical and subcortical regions. In conclusion, it can be stated that the STN has anatomically a central position within the basal ganglia thalamocortical associative and limbic circuits and is functionally a potent regulator of these pathways.     

Impairment of movement initiation and execution but not preparation in idiopathic dystonia

Imaging studies have reported impaired activation of the striatum and their frontal projection sites in dsytonia, areas which are considered to play a role in motor preparation, movement initiation and execution. The aim of this study was to investigate the processes of motor preparation, response initiation and execution in patients with idiopathic torsion dystonia (ITD). We assessed 12 patients with ITD and 12 age-matched controls on a number of reaction time (RT) tasks that differed in degree of motor preparation possible. Subjects performed a visual simple RT (SRT) task, an uncued four-choice reaction time (CRT) task and a fully precued four-choice RT task. A stimulus 1-stimulus 2 (S1-S2) paradigm was used. The warning signal/precue (S1) preceded the imperative stimulus (S2) by either 0 ms (no warning signal or precue) 200 ms, 800 ms, 1,600 ms or 3,200 ms. The patients with ITD had significantly slower RTs and movement times than normals across all RT tasks. The unwarned SRT trials were significantly faster than the uncued CRT trials for both groups. For both groups, precued CRTs were significantly faster than the uncued CRTs. The results show that while response initiation and execution are significantly slower in patients with ITD than normals, movement preparation is not quantitatively or qualitatively different. The results are discussed in relation to previous imaging, behavioural and electrophysiological studies and models of fronto-striatal dysfunction in ITD.     

Activation of subthalamic neurons by contralateral subthalamic deep brain stimulation in Parkinson disease

Multiple studies have shown bilateral improvement in motor symptoms in Parkinson disease (PD) following unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) and internal segment of the globus pallidus, yet the mechanism(s) underlying this phenomenon are poorly understood. We hypothesized that STN neuronal activity is altered by contralateral STN DBS. This hypothesis was tested intraoperatively in humans with advanced PD using microelectrode recordings of the STN during contralateral STN DBS. We demonstrate alterations in the discharge pattern of STN neurons in response to contralateral STN DBS including short latency, temporally precise, stimulation frequency-independent responses consistent with antidromic activation. Furthermore, the total discharge frequency during contralateral high frequency stimulation (160 Hz) was greater than during low frequency stimulation (30 Hz) and the resting state. These findings demonstrate complex responses to DBS and imply that output activation throughout the basal ganglia-thalamic-cortical network rather than local inhibition is a therapeutic mechanism of DBS.     

Multisensory enhancement: gains in choice and in simple response times

Human observers can detect combinations of multisensory signals faster than each of the corresponding signals presented separately. In simple detection tasks, this facilitation in response times may reflect an enhancement in the perceptual processing stage or/and in the motor response stage. The current study compared the multisensory enhancements obtained in simple and choice response times (SRT and CRT, respectively) in bi- and tri-sensory (audio–visual–haptic) signal combinations using an identical experimental setup that differed only in the tasks—detecting the signals (SRT) or reporting the signals’ location (CRT). Our measurements show that RTs were faster in the multisensory combinations conditions compared to the single stimulus conditions and that the absolute multisensory gains were larger in CRT than in SRT. These results can be interpreted in two ways. According to a serial stages model, the larger multisensory gains in CRT may suggest that when combinations of multisensory signals are presented, an additional enhancement occurs in the cognitive processing stages engaged in the CRT, beyond the enhancement in the perceptual and motor stages common to both SRT and CRT. Alternatively, the results suggest that multisensory enhancement reflect task-dependent interactions within and between multiple processing levels rather than facilitated processing modules. Thus, the larger absolute multisensory gains in CRT may reflect the inverse effectiveness principle, and Bayesian statistics, in that the maximal multisensory enhancements occur in the more difficult (less precise) uni-sensory conditions, i.e., in the CRT.     

Effects of five years of chronic STN stimulation on muscle strength and movement speed

This study examined the long-term effects of chronic subthalamic nucleus (STN) deep brain stimulation (DBS) using both clinical evaluation and laboratory motor control measures. Over a 5-year time period, changes in the motor section of the Unified Parkinson’s Disease Rating Scale (UPDRS) and movement speed and strength at the ankle joint were evaluated on and off STN DBS in eight patients with Parkinson’s disease (PD). Four patients were also studied at the elbow joint. Patients with PD originally received unilateral STN DBS between years 2001 and 2003. They were re-evaluated after 5 years of long-term STN DBS between years 2006–2008. At baseline (year 0) and after 5 years, patients with PD were tested off treatment and on STN DBS. In each testing condition, patients performed ballistic, single degree of freedom ankle dorsiflexion and ankle plantarflexion movements and peak velocity was calculated. Patients also performed maximal voluntary contractions at the ankle joint in both directions, and peak torque was calculated. Results showed increased motor UPDRS scores from year 0 to year 5, but STN DBS was efficacious in reducing them. In contrast to the increase in motor UPDRS scores, motor control results showed a marked improvement in peak velocity and peak torque over the 5-year time period in the off treatment condition, and STN DBS was efficacious by improving both peak velocity and peak torque. The current findings suggest that 5 years of chronic STN DBS can have beneficial effects on the motor system over the long term in discrete motor tasks in which maximal effort and maximal neural output is required.     

Simultaneous repetitive movements following pallidotomy or subthalamic deep brain stimulation in patients with Parkinson's disease

Patients with Parkinson's disease (PD) commonly exhibit difficulties performing simultaneous tasks and levodopa has been shown to improve the performance of these movements to a greater extent than movements performed in isolation. The aim of this study was to compare the effects of acute unilateral pallidal lesions (nine patients) and bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) (eight patients) with levodopa therapy (ten patients) on the performance of isolated versus bilateral simultaneous repetitive movements. The STN group was assessed with and without DBS both on and off levodopa. The two tasks employed were maximally paced button tapping (Tap) and wrist pronation-supination (WPS) movements. During the off drug state (12–14 h after the last oral dose of levodopa), the performance of simultaneous Tap and WPS movements in all three groups was significantly slower and more irregular than when each movement was performed in isolation. For example, WPS velocity decreased by at least 37% (P<0.05) with concomitant Tap. Following levodopa, pallidotomy or STN DBS, WPS velocity was increased during the simultaneous task to a greater extent than in the isolated task. All treatments also improved WPS velocity and increased the regularity of movement during concomitant Tap (P<0.01). The findings indicate that, like levodopa, surgical therapies can improve the performance of simultaneous tasks more than isolated tasks. These observations suggest that the excessive neuronal activity and/or abnormal firing patterns in the globus pallidus internus that is found in parkinsonian patients contribute to difficulties in the execution of complex motor tasks. Electronic Publication     

High frequency stimulation of the subthalamic nucleus evokes striatal dopamine release in a large animal model of human DBS neurosurgery

Subthalamic nucleus deep brain stimulation (STN DBS) ameliorates motor symptoms of Parkinson's disease, but the precise mechanism is still unknown. Here, using a large animal (pig) model of human STN DBS neurosurgery, we utilized fast-scan cyclic voltammetry in combination with a carbon-fiber microelectrode (CFM) implanted into the striatum to monitor dopamine release evoked by electrical stimulation at a human DBS electrode (Medtronic 3389) that was stereotactically implanted into the STN using MRI and electrophysiological guidance. STN electrical stimulation elicited a stimulus time-locked increase in striatal dopamine release that was both stimulus intensity- and frequency-dependent. Intensity-dependent (1–7 V) increases in evoked dopamine release exhibited a sigmoidal pattern attaining a plateau between 5 and 7 V of stimulation, while frequency-dependent dopamine release exhibited a linear increase from 60 to 120 Hz and attained a plateau thereafter (120–240 Hz). Unlike previous rodent models of STN DBS, optimal dopamine release in the striatum of the pig was obtained with stimulation frequencies that fell well within the therapeutically effective frequency range of human DBS (120–180 Hz). These results highlight the critical importance of utilizing a large animal model that more closely represents implanted DBS electrode configurations and human neuroanatomy to study neurotransmission evoked by STN DBS. Taken together, these results support a dopamine neuronal activation hypothesis suggesting that STN DBS evokes striatal dopamine release by stimulation of nigrostriatal dopaminergic neurons.     

Consistent and inconsistent performance in young and elderly adults

Nineteen young adults and 20 nondemented elderly adults participated in simple reaction time (SRT) and choice reaction time (CRT) tasks that vary in processing demands. SRT standard deviation was operationally defined as Consistency, creating a continuum of performance consistency ranging from low consistency (Lo‐C, large SRT standard deviations) to high consistency (Hi‐C, small SRT standard deviations). The SRT task employed 3 preparatory intervals (1,000, 2,000, 3,000 ms), varied randomly across trials to reduce expectancy effects. The lexical decision task (LDT) contained 120 words and 120 pseudowords. Correlational analyses indicated a relation (especially for the elderly) between SRT and CRT performance and other psychometric and neuropsychological measures of mood, vocabulary ability, and digit symbol substitution. Regression analyses examined the relationship between Age, Consistency, SRT, and LDT performance and these psychometric and neuropsychological variables. Age x Consistency interactions were observed, suggesting an additional mechanism (or mechanisms) for slowing in the elderly beyond performance consistency or inconsistency. Relation to the brain reserve capacity theory (Satz, 1993) is discussed.     

Visual reaction time and its relationship to neuropsychological test performance.

The purpose of this study was to investigate the relationship between simple and choice reaction time (RT) measures and neuropsychological test performance (as assessed by the Impairment Index of the Halstead-Reitan Neuropsychological Test Battery). Both median RT scores and intraindividual variability of RT scores were evaluated in three groups: impaired TBI, nonimpaired TBI, and normal controls. In all three groups, there was a statistically significant correlation between both reaction time measures and level of cognitive functioning. In addition, SRT, speed of information processing (as measured by CRT), and intraindividual variability of RT scores continued to be impaired in many brain-damaged individuals who, according to the Impairment Index, had fully recovered from their cognitive deficits. Median RT scores were better able to discriminate between impaired TBI patients and normal controls; but intraindividual variability of RT scores was better able to discriminate between nonimpaired TBI patients and normal controls. It was concluded that, by adding the two short RT tests to the neuropsychological test battery, more accurate predictions can be made about a patient's level of cognitive functioning and the nature of treatment needed for continued recovery.     

A Network Analysis of 15O-H2O PET Reveals Deep Brain Stimulation Effects on Brain Network of Parkinson's Disease

Purpose

As Parkinson''s disease (PD) can be considered a network abnormality, the effects of deep brain stimulation (DBS) need to be investigated in the aspect of networks. This study aimed to examine how DBS of the bilateral subthalamic nucleus (STN) affects the motor networks of patients with idiopathic PD during motor performance and to show the feasibility of the network analysis using cross-sectional positron emission tomography (PET) images in DBS studies.

Materials and Methods

We obtained [¹⁵O]H₂O PET images from ten patients with PD during a sequential finger-to-thumb opposition task and during the resting state, with DBS-On and DBS-Off at STN. To identify the alteration of motor networks in PD and their changes due to STN-DBS, we applied independent component analysis (ICA) to all the cross-sectional PET images. We analysed the strength of each component according to DBS effects, task effects and interaction effects.

Results

ICA blindly decomposed components of functionally associated distributed clusters, which were comparable to the results of univariate statistical parametric mapping. ICA further revealed that STN-DBS modifies usage-strengths of components corresponding to the basal ganglia-thalamo-cortical circuits in PD patients by increasing the hypoactive basal ganglia and by suppressing the hyperactive cortical motor areas, ventrolateral thalamus and cerebellum.

Conclusion

Our results suggest that STN-DBS may affect not only the abnormal local activity, but also alter brain networks in patients with PD. This study also demonstrated the usefulness of ICA for cross-sectional PET data to reveal network modifications due to DBS, which was not observable using the subtraction method.     

Inferring sleep stage from local field potentials recorded in the subthalamic nucleus of Parkinson's patients

Parkinson's disease (PD) is highly comorbid with sleep dysfunction. In contrast to motor symptoms, few therapeutic interventions exist to address sleep symptoms in PD. Subthalamic nucleus (STN) deep brain stimulation (DBS) treats advanced PD motor symptoms and may improve sleep architecture. As a proof of concept toward demonstrating that STN‐DBS could be used to identify sleep stages commensurate with clinician‐scored polysomnography (PSG), we developed a novel artificial neural network (ANN) that could trigger targeted stimulation in response to inferred sleep state from STN local field potentials (LFPs) recorded from implanted DBS electrodes. STN LFP recordings were collected from nine PD patients via a percutaneous cable attached to the DBS lead, during a full night's sleep (6–8 hr) with concurrent polysomnography (PSG). We trained a feedforward neural network to prospectively identify sleep stage with PSG‐level accuracy from 30‐s epochs of LFP recordings. Our model's sleep‐stage predictions match clinician‐identified sleep stage with a mean accuracy of 91% on held‐out epochs. Furthermore, leave‐one‐group‐out analysis also demonstrates 91% mean classification accuracy for novel subjects. These results, which classify sleep stage across a typical heterogenous sample of PD patients, may indicate spectral biomarkers for automatically scoring sleep stage in PD patients with implanted DBS devices. Further development of this model may also focus on adapting stimulation during specific sleep stages to treat targeted sleep deficits.