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. 2015 Mar 1;38(3):473–478. doi: 10.5665/sleep.4512

Bilateral Thalamic Stimulation Induces Insomnia in Patients Treated for Intractable Tremor

Agathe Bridoux 1,2,*,✉, Xavier Drouot 3,4,*, Aude Sangare 1,2, Tarik Al-ani 2, Arnaud Brignol 5, Anais Charles-Nelson 6, Pierre Brugières 7, Gaëtane Gouello 8, Koichi Hosomi 8, Hélène Lepetit 8, Stéphane Palfi 8
PMCID: PMC4335528  PMID: 25515098

Abstract

Study Objectives:

To explore the influence of acute bilateral ventral intermediate thalamic nucleus (VIM) stimulation on sleep.

Design:

Three consecutive full-night polysomnography recordings were made in the laboratory. After the habituation night, a random order for night ON-stim and OFF-stim was applied for the second and third nights.

Setting:

Sleep disorders unit of a university hospital.

Patients:

Eleven patients with bilateral stimulation of the ventral intermediate nucleus of the thalamus (VIM) for drug-resistant tremor.

Measurements:

Sleep measures on polysomnography.

Results:

Total sleep time was reduced during night ON-stim compared to OFF- stim, as well as rapid eye movement sleep percentage while the percentage of N2 increased. Wakefulness after sleep onset time was increased.

Conclusion:

Our results show that bilateral stimulation of the VIM nuclei reduces sleep and could be associated with insomnia.

Citation:

Bridoux A, Drouot X, Sangare A, Al-ani T, Brignol A, Charles-Nelson A, Brugières P, Gouello G, Hosomi K, Lepetit H, Palfi S. Bilateral thalamic stimulation induces insomnia in patients treated for intractable tremor. SLEEP 2015;38(3):473–478.

Keywords: adverse event, deep brain stimulation, insomnia, sleep

INTRODUCTION

Chronic electrical stimulation of the thalamus has been used to treat unilateral or bilateral pharmacoresistant essential tremor for more than 20 y. The anatomical target is the ventral intermediate nucleus (VIM), which is located within the posterior part of the ventrolateral nucleus of the thalamus.1 Recurring clinical observations during postoperative follow-up in our center drew our attention to the fact that nocturnal thalamic stimulation could lead to insomnia in the postoperative period or in patients requiring nighttime stimulation.

The thalamus is a key relay structure of the central nervous system, implicated in integration of sensory inputs and in organization of motor responses. Anatomically, the thalamus is a complex association of specific nuclei, localized in the lateral part of the thalamus, and of nonspecific nuclei, localized in the central part. Specific nuclei integrate distinct sensory and motor modalities and connect these specialized nuclei to the corresponding primary sensory/motor cortical area. The central part of the thalamus is composed of anterior and posterior intralaminar, midline nuclei, and the paralaminar portion of the specific nuclei. These central nuclei are interposed between brainstem arousal systems and the supervisory frontal system and are known to adjust the levels of vigilance and alertness.

Thalamic neuron activity is closely linked to the state of vigilance and sleep. Extensive experimental unilateral2 and bilateral3,4 lesions in various thalamic nuclei frequently suppress sleep. Severe insomnia and isolated suppression of spindle waves have been observed in patients with degenerative,5 vascular,6,7 and surgical8 lesions of the thalamus. The specific involvement of the different thalamic nuclei in vigilance and sleep cannot be deduced from these studies because precise extension of the lesion is difficult to determine. Nevertheless, the central nuclei seem to play a major role in arousal shifts. Electrophysiological stimulation of these regions leads to the so-called cortical recruiting effect of Moruzzi and Magoun9 and desynchronizes the slow large amplitude electroencephalography (EEG) waves of anesthetized cats. Low-frequency stimulation induces slow waves in the entire cortical mantle accompanied by somnolence, whereas high-frequency stimulation results in desynchronized cortical activity and arousal.10,11 In contrast, restricted injuries to the central thalamus may produce a severe and prolonged hypovigilance state such as coma.12 However, functional imaging studies have shown that activation of thalamic nuclei is related to higher levels of wakefulness. Electrical stimulation of thalamic central nuclei has been shown to strengthen and to facilitate the functional arousal mode in animals,13 a prerequisite of awareness. Thus, central thalamic nuclei may serve to generate a degree of cortical activation that would suffice to maintain a high level of vigilance.

Although the mechanisms of deep brain stimulation are not well established, several studies have underlined the involvement of pathways surrounding the targeted nucleus. For example, Gradinaru et al.14 demonstrated that activation of corticofugal fibers was involved in the anti-parkinsonian effects of subthalamic nucleus stimulation. Although VIM is not implicated in vigilance, the central part of the thalamus and intra-laminar nuclei are involved in arousal regulation, are located proximal to the VIM, and could be affected by the electrical impulsions arising from an electrode localized in the VIM nucleus.

To our knowledge, only one previous study has tested the effect of VIM high-frequency stimulation on sleep in patients with essential tremor and Parkinson disease.15 Arnulf et al.15 did not find any change in sleep time and sleep quality but stimulation was unilateral in five of six patients and bilateral in only one patient. In our work, we explored a possible influence of bilateral VIM stimulation on sleep and acutely quantified an unreported adverse event of thalamic stimulation. The objective of our study was to compare sleep parameters when stimulation was OFF and ON in patients treated with bilateral VIM stimulation for tremor.

METHODS

Patients

The current study described a clinical investigation performed to analyze an unexpected adverse event observed following a routine functional neurosurgical procedure. Appropriate ethics approvals were received prior to study initiation.

Thirteen consecutive patients underwent bilateral VIM thalamus stimulation for bilateral tremor and 11 patients agreed to undergo assessment of their sleep disorder. Two patients had idiopathic Parkinson disease (#2, #5) and the other nine patients had essential tremor (Table 1). These patients did not suffer from severe sleep apnea syndrome or psychiatric disorders, and did not take drugs interfering with sleep (tricyclic agents, selective serotonin reuptake inhibitor, and benzodiazepines). Usual treatments were maintained throughout the sleep assessment, including levodopa (50–150 mg/day) and piribédil (20 mg/day) for Parkinson disease and propanolol (40 mg/day) for two patients with essential tremor. Clinical characteristics of patients are shown in Table 1. Sleep recordings were performed from 8 w to 18 mo after surgical implantation and only once were optimal stimulation parameters for suppression of tremor found. Sleep quality the month preceding sleep recording was evaluated by the Pittsburgh Sleep Quality Index.16 The level of daytime sleepiness was evaluated by the Epworth Sleepiness Scale.17

Table 1.

Clinical characteristics of the 11 patients.

graphic file with name aasm.38.3.473.t01.jpg

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Nocturnal Sleep Recordings

Three full-night polysomnography (PSG) recordings were performed during 3 successive days in the sleep laboratory: (1) sleep assessment started with 1 habituation night; (2) 1 night with stimulator ON (night “ON-stim”); and (3) 1 night with stimulator OFF (night “OFF-stim”). The night ON-stim and night OFF-stim were randomized to avoid order effect (Figure 1).

Figure 1.

Figure 1

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Experiment description with night randomization.

The three full-night recordings were obtained using a Morpheus digital recorder (Morpheus System; Micromed, Mogliano Veneto (TV), Italy) with six EEG channels (F3-A1, F4-A2, C4-A1, C3-A2, O2-A1, and O1-A2), a chin electromyo-gram, two electrooculograms, and submental electromyography. For the habituation night, respiratory signals (oronasal flow, oxygen saturation, thoracic and abdominal belts) were also recorded. Signals were continuously displayed on a computer screen and checked regularly. Sampling rates were at least two times the stimulation frequency (130–180 Hz) and range from 260 Hz to a maximum of 1,024 Hz. For the night OFF-stim, the battery was switched OFF just after dinner and was switched ON for breakfast. The EEG signal was analyzed visually by a trained observer on filtered EEG at 0.49–20 Hz to minimize artifacts of stimulation. Recordings started from 21:00 and patients were awakened at 07:00.

Sleep scoring (nonrapid eye movement sleep: N1, N2, N3, and rapid eye movement (REM) sleep) was performed according to Rechtschaffen and Kales criteria revised by the American Academy of Sleep Medicine.18,19 PSGs recorded with stimulator ON were submitted to an artifact subtraction before sleep analysis (see next paragraph). Therefore, the scorer was blinded to the stimulator condition. We compared the average of total sleep time, sleep efficiency, and total sleep period in conditions ON-stim and OFF-stim.

EEG Spectral Analysis

Artifacts' Rejection

The monopolar stimulation produced on EEG signals a high-amplitude artifact. This artifact is of constant amplitude, with a known and stable frequency (i.e., frequency delivered by the stimulator) corresponding to a Dirac-like impulse. To remove these artifacts, we developed a Matlab (2008b, The Math-Works, Natwick, MA) algorithm, adapted from a previously validated algorithm20 and based on empirical mode decomposition (EMD).21 Basic EMD is defined by a process called sifting, which breaks down any multimodal signal to a sum of basis components called intrinsic mode functions (IMFs). The IMFs are zero-mean amplitude modulation-frequency modulation, e.g., AM-FM signals that must fulfill two conditions: the first is that the number of extrema and that of zero-crossing must differ at most by one; the second is that at any data point, the mean value of the upper and lower envelopes is zero. The artifacted raw EEG was submitted to EMD decomposition. A spectral analysis of IMF allows for determination of the frequency composition of each IMF.

The IMF containing a frequency peak around the stimulation rate was identified as artifact IMF. The clean signals were then reconstructed by calculating the sum of all the remaining IMFs except for the artifact IMF containing the artifact and harmonics (Figure 2).

Figure 2.

Figure 2

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Illustration of artifact subtraction on night ON-stim electroencephalography. (A) One epoch of artifacted signal from channel F3-A1 (sleep stage N3), before processing. (B) Power spectrum in spectral power of the signal before processing. Note the peak at 165 Hz corresponding to the stimulation and the peak at 60 Hz corresponding to environmental noise. (C) Aspect of the signal of the same epoch after artifact subtraction. (D) Power spectrum in spectral power of the signal after processing. The peaks corresponding to artifacts have been removed. Power, scaled by the sampling frequency was obtained by Matlab (2008b, The MathWorks, Natwick, MA) built-in Welch algorithm.

Power Spectral Analysis During Sleep: Measure of Slow Wave Activity

Slow wave activity (SWA) is a validated tool to quantify the depth of SWS.22 We measured SWA on two derivations on the left and right hemisphere (C3-A2, 01-A2, and C4-A1; O2-A1) as the absolute power (μV2) of the delta band (0.49–3.9 Hz) during the first three sleep cycles defined as previously published.23 Epochs with movement artifact were visually identified and discarded. Power spectra were calculated with fast Fourier transform, through a Hanning window between 256- and 1,024-point segments depending of the sampling rate, yielding a 0.098-Hz resolution, on EEG signals previously submitted to artifact subtraction. To assess the effect of thalamic stimulation on slow wave sleep, we compared SWA in night ON-stim and night OFF-stim. We chose to analyze three cycles because some patients have a short time of sleep and no more than three sleep cycles during ON-stim night.

Surgical Procedure and Stimulation Parameters

Stereotactic techniques were used to target the VIM. DBS quadripolar electrodes (Medtronic 3387; Medtronic, Inc., priate., MN) were implanted bilaterally for chronic high-frequency stimulation (130–180 Hz, 60–90 μsec pulse width, 2.5 V, quadripolar, contact 0 negative, battery positive). Each of the four electrodes' contacts was tested for adverse reactions and clinical benefits under locoregional anesthesia. The electrodes were then connected to a pulse generator (Kinetra, Medtronic, MN) that was implanted in the infraclavicular or abdominal region under general anesthesia. Positions of active plots for each patient are illustrated in Figure 3.

Figure 3.

Figure 3

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Frontal section 3 mm, 5 mm, 7 mm, and 9 mm posterior to the middle of the AC-PC (anterior commissure-posterior commissure) line. Localization of the electrodes implanted (n = 7). The contacts of each electrode are superimposed on the atlas of Schaltenbrand and Wahren (1977) using Cerefy® Clinical Brain Atlas software (2005, Thieme, Stuttgart, Germany).

Statistics

Data were expressed as mean ± standard error of the mean. The crossover design enabled each subject to serve as his or her own control. Outcomes were analyzed using a linear mixed design. This design included the patient as a random effect and took into account the correlation between the two measurements in the same patient during each period as well as night order and stimulation status. The interactions between night order and stimulation status were compared using the likelihood ratio test. A restricted maximum likelihood estimation procedure was used. Statistical significance was set at P < 0.05.

RESULTS

Patients and Clinical Evaluation

High-frequency stimulation successfully suppressed tremor in all patients. At the time of data collection, all stimulators were set in a cycling mode, and switched OFF automatically at night. The quality of sleep before surgery assessed with Pittsburgh Sleep Quality Index ranged from moderate disruption to very bad sleep (range, 3 to 16). All patients had normal daytime vigilance as estimated with the Epworth Sleepiness Scale (Table 1).

Nocturnal Sleep Recordings

Entire data were available for only 8 of 11 patients (#1 to #8) due to technical problems in 2 patients (#9, #11). A third patient asked us to switch ON the stimulator in the middle of the night OFF-stim due to tremor resurgence (#10).

Night random order was ON-OFF for four patients and OFF-ON in the other four. Only the parameters for the second and the third night were analyzed. Average total sleep time (Figure 4) and average total sleep period were significantly shorter and average sleep efficiency was lower during night ON-stim than during night OFF-stim (Table 2).

Figure 4.

Figure 4

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Polysomnography data. Nocturnal sleep recordings: total sleep times in minutes for nights OFF-stim and ON-stim. * P ≤ 0.05 (n = 8). Black line = average value of total sleep time for all patients.

Table 2.

Effect of the ventrointermediate nucleus of the thalamus stimulation on nocturnal sleep parameters for the second and third night for height patients (#1 to #8).

graphic file with name aasm.38.3.473.t02.jpg

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Wake after sleep onset (% of total sleep period) was significantly higher, N1 duration (% of total sleep time [TST]) and N3 duration were unchanged, N2 duration was significantly increased (% TST) and REM duration (% TST) was significantly lower during night ON-stim compared to night OFF-stim.

N1, N2, N3, and REM sleep latencies were not significantly different during night ON-stim and night OFF-stim (Table 2).

Power Spectral Analysis during Sleep: Measure of SWA

The absolute power (μV2) in the delta band of the N3 did not differ significantly between the night ON-stim compared to the night OFF-stim on central and occipital leads of both hemispheres.

DISCUSSION

Our results showed that bilateral high-frequency stimulation of the thalamus was associated with a significant reduction of nighttime sleep in the eight patients treated for intractable tremor and Parkinson disease. This is the first compelling characterization of such sleep disturbances following bilateral thalamic high-frequency stimulation for invalidating tremor. Thus, our results show that bilateral thalamic stimulation affected sleep because mean TST was lower during the night ON-stim compared to the night OFF-stim.

This finding is in contrast with those of Arnulf et al.,15 who previously investigated the effect of thalamic stimulation on sleep time and quality. These authors found no effect of high- frequency thalamic stimulation on TST in a very similar group of six patients in whom stimulation was unilateral (n = 5) and bilateral (n = 1).15 It is likely in this case that bilateral stimulation could explain these discrepancies. Although also noted after unilateral thalamotomy, reduction of nocturnal sleep has been reported to be more accentuated after bilateral thalamotomy.8 The involvement of bilateral thalami is also suggested by the occurrence of a severe and prolonged insomnia immediately after a right VIM thalamotomy in a patient who had discontinued VIM thalamic stimulation years before.24 Furthermore, severe insomnia is a core symptom in fatal familial insomnia, a neurodegenerative disease characterized by bilateral thalamic degeneration.5 Therefore, we believe that, when applied bilaterally, VIM stimulation may lead to shortened sleep. We have cautiously quantified the effects of VIM stimulation on sleep recordings. Nevertheless, we have not been able to demonstrate that bilateral high-frequency stimulation reduces sleep depth.

The use of randomization for each PSG strengthens our results and limits the effect of night 1 over night 2. Randomization is crucial in this case because a short night is known to alter the sleep duration and sleep composition of the following night. We found that TST during night ON-stim was lower in all patients (except one), whatever the first condition night.

Furthermore, the habituation night prevents results from being contaminated by first-night effects. Our findings are likely due to thalamic stimulation rather than environmental habituation. Furthermore, we used a validated technique to subtract stimulation artifact on contaminated EEG.20 The scorer was then blinded to the stimulation conditions, allowing an objective visual sleep analysis. The main limitation of our data analysis was related to the unblinded sleep evaluation toward stimulation conditions. In fact, double blind evaluation comparing stimulation ON-stim and OFF-stim is not possible for these patients. Indeed, all patients with tremor are usually able to guess which assessments are performed with or without stimulators because of the clinically obvious beneficial effects of stimulation.25

Other factors could have reduced nocturnal sleep time. Expected adverse events of thalamic stimulation such as paresthesia or anxiety have been reported26,27 and could have prevented good nighttime sleep or sleep initiation during naps. However, none of our patients complained about these adverse events. In addition, the negative emotions evaluated by the Nottingham Health Profile in essential tremor have been reported to be improving after bilateral thalamus stimulation.28 In that case, mood disorders might not account for our sleep results. We believe that the reduced sleep time is likely due to a direct effect of stimulation rather than an indirect awaking effect through mood or sensory symptoms.

We compared sleep in a bilateral OFF-stim and bilateral ON-stim condition. For this reason we cannot be strictly sure that the observed effect is due to bilateral stimulation. Notably, insomnia could also be provoked by unilateral lesion of the left thalamus2–6 and we cannot formally exclude that the insomnia effect of the bilateral stimulation is related to the left stimulation alone.

Keeping in mind that (1) we observed a reduction of TST, as well as REM sleep but not N1, N2, and N3 stage, (2) sleep depth is not reduced in ON-stim night compared to OFF-stim night, and (3) we observed increased wake time after sleep onset without any change of sleep onset latency, our results suggest that bilateral thalamic stimulation may interfere with the circadian system, thereby leading to insomnia.

The suprachiasmatic nucleus of the hypothalamus serves as “a master clock” that regulates several physiological processes including sleep and wake.29 It is likely that the process underlying insomnia could be linked to VIM stimulation by affecting the descending fibers to the hypothalamus. It would not be due to electrode implantation because insomnia appeared only during the ON-stim night and disappeared after the stimulator was switched off. In the clinical report of both patients with pharmacological resistant headache, direct posterior hypothalamus stimulation led to an alteration of the patients' sleep patterns, suggesting that hypothalamus stimulation induced change in sleep patterns. The hypnograms after stimulation demonstrated disrupted sleep and a prolonged period of wakefulness after midnight in both patients.30

Our findings may have clinical implications. Although the stimulator is usually switched off during the night to spare the battery, our results strengthen the rule that stimulator should be set in a cycling mode with a nighttime OFF period to avoid sleep disturbances.

CONCLUSION

Our study suggests that high-frequency bilateral VIM-stimulation affects TST and sleep efficiency, and increases wake time after sleep onset and could lead to insomnia. This needs to be considered as a stimulation-related side effect of VIM stimulation.

DISCLOSURE STATEMENT

This was not an industry supported study. The authors have indicated no financial conflicts of interest. This work was performed at APHP, Hospital Henri Mondor, Créteil, France.

ACKNOWLEDGMENTS

The authors thank Bechir Jarraya and Ala Covali-Noroc for their invaluable help in this study. We also wish to thank Jeffrey Arsham, an American medical translator, for reviewing and editing the English-language manuscript. The study was partially supported by Association pour la recherche sur la stimulation cérébrale-ARSC, ARSC Foundation.

REFERENCES

  • 1.Benabid AL, Pollak P, Louveau A, Henry S, de Rougemont J. Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. Appl Neurophysiol. 1987;50:344–6. doi: 10.1159/000100803. [DOI] [PubMed] [Google Scholar]
  • 2.Angeleri F, Marchesi GF, Quattrini A. Effects of chronic thalamic lesions on the electrical activity of the neocortex and on sleep. Arch Ital Biol. 1969;107:633–67. [Google Scholar]
  • 3.Naquet R, Denavit M, Lanoir J, Albe-Fessard D. Altérations transitoires ou définitives des zones diencephaliques chez le chat. Leur effets sur l'activité corticale et le sommeil. In: Jouvet M, editor. Aspects anatomo-Fonctionnels de la physiologie du sommeil. Paris: Edition du centre National de la Recherche Scientifique; 1965. pp. 107–31. [Google Scholar]
  • 4.Villablanca J, Salinas-Zeballos ME. Sleep-wakefulness, EEG and behavioral studies of chronic cats without the thalamus: the ‘athalamic’ cat. Arch Ital Biol. 1972;110:383–411. [PubMed] [Google Scholar]
  • 5.Lugaresi E, Medori R, Montagna P, et al. Fatal familial insomnia and dysautonomia with selective degeneration of thalamic nuclei. N Engl J Med. 1986;315:997–1003. doi: 10.1056/NEJM198610163151605. [DOI] [PubMed] [Google Scholar]
  • 6.Garrel S, Fau R, Perret J, Chatelain R. Troubles du sommeil dans deux syndromes vasculaires du tronc cerebral dont l'un anatomo-clinique. Rev Neurol. 1966;115:575–84. [PubMed] [Google Scholar]
  • 7.Schott B, Michel D, Mouret J, Renaud B, Quenin P, Tomasi M. Monoamines et regulation de la vigilance. II. Syndromes lesionnels du systeme nerveux central. Rev Neurol. 1972;127:157–71. [PubMed] [Google Scholar]
  • 8.Bricolo A. Insomnia after bilateral stereotactic thalamotomy in man. J Neurol Neurosurg Psychiatry. 1967;30:154–8. doi: 10.1136/jnnp.30.2.154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Moruzzi G, Magoun HW. Brain stem reticular formation and activation of the EEG. Electroencephalogr Clin Neurophysiol. 1949;1:455–73. [PubMed] [Google Scholar]
  • 10.Hunter J, Jasper HH. Effects of thalamic stimulation in unanaesthetised animals; the arrest reaction and petit mal-like seizures, activation patterns and generalized convulsions. Electroencephalogr Clin Neurophysiol. 1949;1:305–24. doi: 10.1016/0013-4694(49)90043-7. [DOI] [PubMed] [Google Scholar]
  • 11.Jasper H. Diffuse projection systems: the integrative action of the thalamic reticular system. Electroencephalogr Clin Neurophysiol. 1949;1:405–19. discussion 19–20. [PubMed] [Google Scholar]
  • 12.Castaigne P, Lhermitte F, Buge A, Escourolle R, Hauw JJ, Lyon-Caen O. Paramedian thalamic and midbrain infarct: clinical and neuropathological study. Ann Neurol. 1981;10:127–48. doi: 10.1002/ana.410100204. [DOI] [PubMed] [Google Scholar]
  • 13.Shirvalkar P, Seth M, Schiff ND, Herrera DG. Cognitive enhancement with central thalamic electrical stimulation. Proc Natl Acad Sci U S A. 2006;103:17007–12. doi: 10.1073/pnas.0604811103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Gradinaru V, Mogri M, Thompson KR, Henderson JM, Deisseroth K. Optical deconstruction of parkinsonian neural circuitry. Science. 2009;324:354–9. doi: 10.1126/science.1167093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Arnulf I, Bejjani BP, Garma L, et al. Effect of low and high frequency thalamic stimulation on sleep in patients with Parkinson's disease and essential tremor. J Sleep Res. 2000;9:55–62. doi: 10.1046/j.1365-2869.2000.00171.x. [DOI] [PubMed] [Google Scholar]
  • 16.Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28:193–213. doi: 10.1016/0165-1781(89)90047-4. [DOI] [PubMed] [Google Scholar]
  • 17.Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14:540–5. doi: 10.1093/sleep/14.6.540. [DOI] [PubMed] [Google Scholar]
  • 18.Rechstchaffen A, Kales A. Los Angeles, CA: UCLA Brain Information Service/Brain Research Institute; 1968. A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. [Google Scholar]
  • 19.Silber MH, Ancoli-Israel S, Bonnet MH, et al. The visual scoring of sleep in adults. J Clin Sleep Med. 2007;3:121–31. [PubMed] [Google Scholar]
  • 20.Al-ani T, Cazettes F, Palfi S, Lefaucheur JP. Automatic removal of high-amplitude stimulus artefact from neuronal signal recorded in the subthalamic nucleus. J Neurosci Methods. 2011;198:135–46. doi: 10.1016/j.jneumeth.2011.03.022. [DOI] [PubMed] [Google Scholar]
  • 21.Huang NE, Shen Z, Long SR, et al. The empirical mode decomposition and Hilbert spectrum for nonlinear and non stationary time series analysis. Proc R Soc London. 1998a;454:903–95. [Google Scholar]
  • 22.Dang-Vu T, Schabus TM, Desseilles M, et al. Spontaneous neural activity during human slow wave sleep. Proc Natl Acad Sci U S A. 2008;105:15160–5. doi: 10.1073/pnas.0801819105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Feinberg I, March JD. Cyclic delta peaks during sleep: tesult of a pulsatile endocrine process? Arch Gen Psychiatry. 1988;45:1141–2. doi: 10.1001/archpsyc.1988.01800360089015. [DOI] [PubMed] [Google Scholar]
  • 24.Quigg M, Frysinger RC, Harrison M, Elias WJ. Acute insomnia following surgery of the ventralis intermedius nucleus of the thalamus for tremor. J Clin Sleep Med. 2007;3:58–9. [PubMed] [Google Scholar]
  • 25.Kumar R, Lozano AM, Kim YJ, et al. Double-blind evaluation of subthalamic nucleus deep brain stimulation in advanced Parkinson's disease. Neurology. 1998;51:850–5. doi: 10.1212/wnl.51.3.850. [DOI] [PubMed] [Google Scholar]
  • 26.Pahwa R, Lyons K, Koller WC. Surgical treatment of essential tremor. Neurology. 2000;54:S39–44. [PubMed] [Google Scholar]
  • 27.Pizzolato G, Mandat T. Deep brain stimulation for movement disorders. Front Integr Neurosci. 2012;6:2. doi: 10.3389/fnint.2012.00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Graff-Radford J, Foote KD, Mikos AE, et al. Mood and motor effects of thalamic deep brain stimulation surgery for essential tremor. Eur J Neurol. 2010;17:1040–6. doi: 10.1111/j.1468-1331.2010.02958.x. [DOI] [PubMed] [Google Scholar]
  • 29.Kovac S, Wright MA, Eriksson SH, Zrinzo L, Matharu M, Walker MC. The effect of posterior hypothalamus region deep brain stimulation on sleep. Cephalalgia. 2013;34:219–23. doi: 10.1177/0333102413505241. [DOI] [PubMed] [Google Scholar]
  • 30.Saper CB, Scammell TE, Lu J. Hypothalamic regulation of sleep and circadian rhythms. Nature. 2005;437:1257–63. doi: 10.1038/nature04284. [DOI] [PubMed] [Google Scholar]

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