Asymmetric right/left encoding of emotions in the human subthalamic nucleus

Renana Eitan, Reuben R Shamir, Eduard Linetsky, Ovadya Rosenbluh, Shay Moshel, Tamir Ben-Hur, Hagai Bergman, Zvi Israel, Renana Eitan, Reuben R Shamir, Eduard Linetsky, Ovadya Rosenbluh, Shay Moshel, Tamir Ben-Hur, Hagai Bergman, Zvi Israel

Abstract

Emotional processing is lateralized to the non-dominant brain hemisphere. However, there is no clear spatial model for lateralization of emotional domains in the basal ganglia. The subthalamic nucleus (STN), an input structure in the basal ganglia network, plays a major role in the pathophysiology of Parkinson's disease (PD). This role is probably not limited only to the motor deficits of PD, but may also span the emotional and cognitive deficits commonly observed in PD patients. Beta oscillations (12-30 Hz), the electrophysiological signature of PD, are restricted to the dorsolateral part of the STN that corresponds to the anatomically defined sensorimotor STN. The more medial, more anterior and more ventral parts of the STN are thought to correspond to the anatomically defined limbic and associative territories of the STN. Surprisingly, little is known about the electrophysiological properties of the non-motor domains of the STN, nor about electrophysiological differences between right and left STNs. In this study, microelectrodes were utilized to record the STN spontaneous spiking activity and responses to vocal non-verbal emotional stimuli during deep brain stimulation (DBS) surgeries in human PD patients. The oscillation properties of the STN neurons were used to map the dorsal oscillatory and the ventral non-oscillatory regions of the STN. Emotive auditory stimulation evoked activity in the ventral non-oscillatory region of the right STN. These responses were not observed in the left ventral STN or in the dorsal regions of either the right or left STN. Therefore, our results suggest that the ventral non-oscillatory regions are asymmetrically associated with non-motor functions, with the right ventral STN associated with emotional processing. These results suggest that DBS of the right ventral STN may be associated with beneficial or adverse emotional effects observed in PD patients and may relieve mental symptoms in other neurological and psychiatric diseases.

Keywords: Parkinson's disease; deep brain stimulation (DBS); emotions; spikes; subthalamic nucleus.

Figures

Figure 1
Figure 1
STN trajectory and analysis of microelectrode recordings (MER). The parasagittal plane of the STN (atlas of Schaltenbrand and Wahren, 1977) is represented at laterality of 12 mm with respect to the AC-PC line. Normalized root mean square (NRMS) was computed on the MER to delineate the STN boundaries (upper image). The x-axis is the estimated distance of MER from the STN target as defined on the pre-operative MRI image. Power spectral density was computed at each MER site, and a spectrogram visualizing the change of oscillatory activity with location before and within the STN is presented (lower image).
Figure 2
Figure 2
Emotions recognition accuracy. Medicated Parkinson's disease (PD) patients (n = 13) compared with three healthy control (HC) groups: (1) average age and gender (male/female) ratio matched (AGM) group (n = 12); (2) 60 years old or older (n = 14), and; (3) younger than 60 years old (n = 15). Error bars represent standard error of the mean (SEM). *p < 0.05 (t-test) statistical significant difference between the PD patients and each of the tested healthy control groups.
Figure 3
Figure 3
Peri-stimulus time histograms (PSTH) and event related desynchronization (ERD) of two simultaneous microelectrodes recordings (MER) of the right subthalamic nucleus. Data of patient #3 from the dorso-lateral oscillatory region (left column) and the ventro-medial non-oscillatory region (right column) during emotive stimulation with 44 voices (introduced at time = 0): (A) average Z-score of the root mean square (RMS). The light shadowing is the standard error of the mean (SEM). (B) Average power spectrum density (PSD); and (C) average event related desynchronization (ERD).
Figure 4
Figure 4
A comparison of responses to emotive stimulation in different subthalamic nucleus (STN) regions. (A) Left and right dorso-lateral oscillatory regions (DLOR, 14 STNs, 18 data segments, and 11 STNs, 13 data segments, respectively). (B) Left and right ventro-medial non-oscillatory regions (VMNR, 14 STNs, 19 data segments, and 11 STNs, 21 data segments, respectively). Significant increases in the background activity, and reduced oscillatory activity was observed in the VMNR of the right STN after vocal emotional stimuli (B, right), but not in the left VMNR (B, left) or left or right STN DLOR (A). Solid line represents the response mean, and shaded area represents the standard error of the mean (SEM).
Figure 5
Figure 5
A comparison of responses to emotive stimulation in subthalamic nucleus (STN) regions. (A) Left and right dorso-lateral oscillatory regions (DLOR), 5 STNs, 7 data segments, and 3 STNs, 4 data segments, respectively. (B) Left and right ventro-medial non-oscillatory regions (VMNR, 5 STNs, 8 data segments, and 4 STNs, 10 data segments, respectively). A steep reduction in the oscillatory activity is present in the right STN VMNR for positive voices (B, right), but not for neutral voices and less for negative voices. Such responses are not observed for emotive voice stimuli in the left VMNR (B, left) or left or right STN DLOR (A). Color coding: Red, green, and blue responses to negative, neutral, and positive emotive voices, respectively. Solid lines represent the mean of the event related desynchronization change (ERD), and the surrounding shaded area represents the response standard error of the mean (SEM).
Figure 6
Figure 6
Preoperative emotion recognition accuracy is related to the intraoperative responses at the right subthalamic nucleus (STN) ventro-medial non-oscillatory region (VMNR). Each “+” represents a response to a single voice presentation. Significant correlations were observed between the preoperative emotion recognition accuracy and changes in STN background activity (e.g., Z score), and changes in oscillatory activity [e.g., event related de-synchronization (ERD)].

References

    1. Abosch A., Hutchison W. D., Saint-Cyr J. A., Dostrovsky J. O., Lozano A. M. (2002). Movement-related neurons of the subthalamic nucleus in patients with Parkinson disease. J. Neurosurg. 97, 1167–1172 10.3171/jns.2002.97.5.1167
    1. Alba-Ferrara L., Ellison A., Mitchell R. L. C. (2011). Decoding emotional prosody: resolving differences in functional neuroanatomy from fMRI and lesion studies using TMS. Brain Stimul. 5, 347–353 10.1016/j.brs.2011.06.004
    1. Anzak A., Gaynor L., Beigi M., Limousin P., Hariz M., Zrinzo L., et al. (2011). A gamma band specific role of the subthalamic nucleus in switching during verbal fluency tasks in Parkinson's disease. Exp. Neurol. 232, 136–142 10.1016/j.expneurol.2011.07.010
    1. Assogna F., Pontieri F. E., Cravello L., Peppe A., Pierantozzi M., Stefani A., et al. (2010). Intensity-dependent facial emotion recognition and cognitive functions in Parkinson's disease. J. Int. Neuropsychol. Soc. 16, 867–876 10.1017/S1355617710000755
    1. Bayer H. M., Glimcher P. W. (2005). Midbrain dopamine neurons encode a quantitative reward prediction error signal. Neuron 47, 129–141 10.1016/j.neuron.2005.05.020
    1. Belin P., Fillion-Bilodeau S., Gosselin F. (2008). The Montreal Affective Voices: a validated set of nonverbal affect bursts for research on auditory affective processing. Behav. Res. Methods 40, 531–539 10.3758/BRM.40.2.531
    1. Benabid A. L., Pollak P., Gross C., Hoffmann D., Benazzouz A., Gao D. M., et al. (1994). Acute and long-term effects of subthalamic nucleus stimulation in Parkinson's disease. Stereotact. Funct. Neurosurg. 62, 76–84 10.1159/000098600
    1. Benazzouz A., Breit S., Koudsie A., Pollak P., Krack P., Benabid A.-L. (2002). Intraoperative microrecordings of the subthalamic nucleus in Parkinson's disease. Mov. Disord. 17, S145–S149 10.1002/mds.10156
    1. Benazzouz A., Gross C., Féger J., Boraud T., Bioulac B. (1993). Reversal of rigidity and improvement in motor performance by subthalamic high-frequency stimulation in MPTP-treated monkeys. Eur. J. Neurosci. 5, 382–389 10.1111/j.1460-9568.1993.tb00505.x
    1. Biseul I., Sauleau P., Haegelen C., Trebon P., Drapier D., Raoul S., et al. (2005). Fear recognition is impaired by subthalamic nucleus stimulation in Parkinson's disease. Neuropsychologia 43, 1054–1059 10.1016/j.neuropsychologia.2004.10.006
    1. Bódi N., Kéri S., Nagy H., Moustafa A., Myers C. E., Daw N., et al. (2009). Reward-learning and the novelty-seeking personality: a between- and within-subjects study of the effects of dopamine agonists on young Parkinson's patients. Brain 132, 2385–2395 10.1093/brain/awp094
    1. Bronstein J. M., Tagliati M., Alterman R. L., Lozano A. M., Volkmann J., Stefani A., et al. (2011). Deep brain stimulation for Parkinson disease: an expert consensus and review of key issues. Arch. Neurol. 68, 165 10.1001/archneurol.2010.260
    1. Brücke C., Kupsch A., Schneider G.-H., Hariz M. I., Nuttin B., Kopp U., et al. (2007). The subthalamic region is activated during valence-related emotional processing in patients with Parkinson's disease. Eur. J. Neurosci. 26, 767–774 10.1111/j.1460-9568.2007.05683.x
    1. Brunenberg E. J. L., Moeskops P., Backes W. H., Pollo C., Cammoun L., Vilanova A., et al. (2012). Structural and resting state functional connectivity of the subthalamic nucleus: identification of motor STN parts and the hyperdirect pathway. PLoS ONE 7:e39061 10.1371/journal.pone.0039061
    1. Buot A., Welter M.-L., Karachi C., Pochon J.-B., Bardinet E., Yelnik J., et al. (2012). Processing of emotional information in the human subthalamic nucleus. J. Neurol Neurosurg. Psychiatry. [Epub ahead of print]. 10.1136/jnnp-2011-302158
    1. Burbaud P., Clair A.-H., Langbour N., Fernandez-Vidal S., Goillandeau M., Michelet T., et al. (2013). Neuronal activity correlated with checking behaviour in the subthalamic nucleus of patients with obsessive-compulsive disorder. Brain 136, 304–317 10.1093/brain/aws306
    1. Buzsáki G., Anastassiou C. A., Koch C. (2012). The origin of extracellular fields and currents—EEG, ECoG, LFP and spikes. Nat. Rev. Neurosci. 13, 407–420 10.1038/nrn3241
    1. Castner J. E., Chenery H. J., Copland D. A., Coyne T. J., Sinclair F., Silburn P. A. (2007). Semantic and affective priming as a function of stimulation of the subthalamic nucleus in Parkinson's disease. Brain 130, 1395–1407 10.1093/brain/awm059
    1. Castrioto A., Kistner A., Klinger H., Lhommée E., Schmitt E., Fraix V., et al. (2013). Psychostimulant effect of levodopa: reversing sensitisation is possible. J. Neurol. Neurosurg. Psychiatry 84, 18–22 10.1136/jnnp-2012-302444
    1. Chabardès S., Polosan M., Krack P., Bastin J., Krainik A., David O., et al. (2012). Deep brain stimulation for obsessive-compulsive disorder: subthalamic nucleus target. World Neurosurg. 80, S31.e1–S31.e8 10.1016/j.wneu.2012.03.010
    1. Delong M. R., Georgopoulos A. P., Crutcher M. D., Mitchell S. J., Richardson R. T., Alexander G. E. (1984). Functional organization of the basal ganglia: contributions of single-cell recording studies. Ciba Found. Symp. 107, 64–82
    1. Drapier D., Péron J., Leray E., Sauleau P., Biseul I., Drapier S., et al. (2008). Emotion recognition impairment and apathy after subthalamic nucleus stimulation in Parkinson's disease have separate neural substrates. Neuropsychologia 46, 2796–2801 10.1016/j.neuropsychologia.2008.05.006
    1. Dujardin K., Blairy S., Defebvre L., Krystkowiak P., Hess U., Blond S., et al. (2004). Subthalamic nucleus stimulation induces deficits in decoding emotional facial expressions in Parkinson's disease. J. Neurol. Neurosurg. Psychiatry 75, 202–208 10.1136/jnnp.2003.013656
    1. Eusebio A., Witjas T., Cohen J., Fluchère F., Jouve E., Régis J., et al. (2013). Subthalamic nucleus stimulation and compulsive use of dopaminergic medication in Parkinson's disease. J. Neurol. Neurosurg. Psychiatry 84, 868–874 10.1136/jnnp-2012-302387
    1. Follett K. A., Weaver F. M., Stern M., Hur K., Harris C. L., Luo P., et al. (2010). Pallidal versus subthalamic deep-brain stimulation for Parkinson's disease. N. Engl. J. Med. 362, 2077–2091 10.1056/NEJMoa0907083
    1. Frank M. J., Seeberger L. C., O'Reilly R. C. (2004). By carrot or by stick: cognitive reinforcement learning in parkinsonism. Science (New York, N.Y.) 306, 1940–1943 10.1126/science.1102941
    1. Gainotti G. (2012). Unconscious processing of emotions and the right hemisphere. Neuropsychologia 50, 205–218 10.1016/j.neuropsychologia.2011.12.005
    1. Godinho F., Thobois S., Magnin M., Guenot M., Polo G., Benatru I., et al. (2006). Subthalamic nucleus stimulation in Parkinson's disease: anatomical and electrophysiological localization of active contacts. J. Neurol. 253, 1347–1355 10.1007/s00415-006-0222-z
    1. Haynes W. I. A., Haber S. N. (2013). The organization of prefrontal-subthalamic inputs in primates provides an anatomical substrate for both functional specificity and integration: implications for Basal Ganglia models and deep brain stimulation. J. Neurosci. 33, 4804–4814 10.1523/JNEUROSCI.4674-12.2013
    1. Hollerman J. R., Schultz W. (1998). Dopamine neurons report an error in the temporal prediction of reward during learning. Nat. Neurosci. 1, 304–309 10.1038/1124
    1. Huebl J., Schoenecker T., Siegert S., Brücke C., Schneider G.-H., Kupsch A., et al. (2011). Modulation of subthalamic alpha activity to emotional stimuli correlates with depressive symptoms in Parkinson's disease. Move. Disord. 26, 477–483 10.1002/mds.23515
    1. Hutchison W. D., Allan R. J., Opitz H., Levy R., Dostrovsky J. O., Lang A. E., et al. (1998). Neurophysiological identification of the subthalamic nucleus in surgery for Parkinson's disease. Ann. Neurol. 44, 622–628 10.1002/ana.410440407
    1. Joshua M., Adler A., Bergman H. (2010). Novelty encoding by the output neurons of the Basal Ganglia. Front. Syst. Neurosci. 3:20 10.3389/neuro.06.020.2009
    1. Kan Y., Kawamura M., Hasegawa Y., Mochizuki S., Nakamura K. (2002). Recognition of emotion from facial, prosodic and written verbal stimuli in Parkinson's disease. Cortex 38, 623–630 10.1016/S0010-9452(08)70026-1
    1. Kühn A. A., Hariz M. I., Silberstein P., Tisch S., Kupsch A., Schneider G.-H., et al. (2005). Activation of the subthalamic region during emotional processing in Parkinson disease. Neurology 65, 707–713 10.1212/01.wnl.0000174438.78399.bc
    1. Lambert C., Zrinzo L., Nagy Z., Lutti A., Hariz M., Foltynie T., et al. (2012). Confirmation of functional zones within the human subthalamic nucleus: patterns of connectivity and sub-parcellation using diffusion weighted imaging. Neuroimage 60, 83–94 10.1016/j.neuroimage.2011.11.082
    1. Lhommée E., Klinger H., Thobois S., Schmitt E., Ardouin C., Bichon A., et al. (2012). Subthalamic stimulation in Parkinson's disease: restoring the balance of motivated behaviours. Brain 135, 1463–1477 10.1093/brain/aws078
    1. Maia T. V., Frank M. J. (2011). From reinforcement learning models to psychiatric and neurological disorders. Nat. Neurosci. 14, 154–162 10.1038/nn.2723
    1. Mallet L., Polosan M., Jaafari N., Baup N., Welter M.-L., Fontaine D., et al. (2008). Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. N. Engl. J. Med. 359, 2121–2134 10.1056/NEJMoa0708514
    1. Mallet L., Schüpbach M., N'Diaye K., Remy P., Bardinet E., Czernecki V., et al. (2007). Stimulation of subterritories of the subthalamic nucleus reveals its role in the integration of the emotional and motor aspects of behavior. Proc. Natl. Acad. Sci. U.S.A. 104, 10661–10666 10.1073/pnas.0610849104
    1. Mettler F. A., Stern G. M. (1962). Somatotopic localization in rhesus subthalamic nucleus. Arch. Neurol. 7, 328–329 10.1001/archneur.1962.04210040080008
    1. Monakow K. H., Akert K., Künzle H. (1978). Projections of the precentral motor cortex and other cortical areas of the frontal lobe to the subthalamic nucleus in the monkey. Exp. Brain Res. 33, 395–403 10.1007/BF00235561
    1. Moro E., Lozano A. M., Pollak P., Agid Y., Rehncrona S., Volkmann J., et al. (2010). Long-term results of a multicenter study on subthalamic and pallidal stimulation in Parkinson's disease. Move Disord 25, 578–586 10.1002/mds.22735
    1. Morris G., Arkadir D., Nevet A., Vaadia E., Bergman H. (2004). Coincident but distinct messages of midbrain dopamine and striatal tonically active neurons. Neuron 43, 133–143 10.1016/j.neuron.2004.06.012
    1. Moustafa A. A., Herzallah M. M., Gluck M. A. (2013). Dissociating the cognitive effects of levodopa versus dopamine agonists in a neurocomputational model of learning in Parkinson's disease. Neurodegener. Dis. 11, 102–111 10.1159/000341999
    1. Nambu A. (2011). Somatotopic organization of the primate Basal Ganglia. Front. Neuroanat. 5:26 10.3389/fnana.2011.00026
    1. Nambu A., Takada M., Inase M., Tokuno H. (1996). Dual somatotopical representations in the primate subthalamic nucleus: evidence for ordered but reversed body-map transformations from the primary motor cortex and the supplementary motor area. J. Neurosci. 16, 2671–2683
    1. Nambu A., Tokuno H., Takada M. (2002). Functional significance of the cortico-subthalamo-pallidal “hyperdirect” pathway. Neurosci. Res. 43, 111–117 10.1016/S0168-0102(02)00027-5
    1. Odekerken V. J. J., van Laar T., Staal M. J., Mosch A., Hoffmann C. F. E., Nijssen P. C. G., et al. (2013). Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson's disease (NSTAPS study): a randomised controlled trial. Lancet Neurol. 12, 37–44 10.1016/S1474-4422(12)70264-8
    1. Ortega-Cubero S., Clavero P., Irurzun C., Gonzalez-Redondo R., Guridi J., Obeso J. A., et al. (2013). Effect of deep brain stimulation of the subthalamic nucleus on non-motor fluctuations in Parkinson's disease: two-year' follow-up. Parkinsonism Relat. Disord. 19, 543–547 10.1016/j.parkreldis.2013.02.001
    1. Péron J., Biseul I., Leray E., Vicente S., Le Jeune F., Drapier S., et al. (2010a). Subthalamic nucleus stimulation affects fear and sadness recognition in Parkinson's disease. Neuropsychology 24, 1–8 10.1037/a0017433
    1. Péron J., Grandjean D., Le Jeune F., Sauleau P., Haegelen C., Drapier D., et al. (2010b). Recognition of emotional prosody is altered after subthalamic nucleus deep brain stimulation in Parkinson's disease. Neuropsychologia 48, 1053–1062 10.1016/j.neuropsychologia.2009.12.003
    1. Péron J., Dondaine T., Le Jeune F., Grandjean D., Vérin M. (2012). Emotional processing in Parkinson's disease: a systematic review. Move. Disord. 27, 186–199 10.1002/mds.24025
    1. Péron J., Frühholz S., Vérin M., Grandjean D. (2013). Subthalamic nucleus: a key structure for emotional component synchronization in humans. Neurosci. Biobehav. Rev. 37, 358–373 10.1016/j.neubiorev.2013.01.001
    1. Piallat B., Polosan M., Fraix V., Goetz L., David O., Fenoy A., et al. (2011). Subthalamic neuronal firing in obsessive-compulsive disorder and Parkinson disease. Ann. Neurol. 69, 793–802 10.1002/ana.22222
    1. Rodriguez-Oroz M. C., Rodriguez M., Guridi J., Mewes K., Chockkman V., Vitek J., et al. (2001). The subthalamic nucleus in Parkinson's disease: somatotopic organization and physiological characteristics. Brain 124, 1777–1790 10.1093/brain/124.9.1777
    1. Romanelli P., Heit G., Hill B. C., Kraus A., Hastie T., Brontë-Stewart H. M. (2004). Microelectrode recording revealing a somatotopic body map in the subthalamic nucleus in humans with Parkinson disease. J. Neurosurg. 100, 611–618 10.3171/jns.2004.100.4.0611
    1. Schaltenbrand G., Wahren W. (1977). Introduction to stereotaxis with an atlas of the human brain. Stuttgart: Thieme
    1. Schroeder U., Kuehler A., Hennenlotter A., Haslinger B., Tronnier V. M., Krause M., et al. (2004). Facial expression recognition and subthalamic nucleus stimulation. J. Neurol. Neurosurg. Psychiatry 75, 648–650 10.1136/jnnp.2003.019794
    1. Schuepbach W. M. M., Rau J., Knudsen K., Volkmann J., Krack P., Timmermann L., et al. (2013). Neurostimulation for Parkinson's disease with early motor complications. N. Engl. J. Med. 368, 610–622 10.1056/NEJMoa1205158
    1. Schultz W., Dayan P., Montague P. R. (1997). A neural substrate of prediction and reward. Science (New York, N.Y.) 275, 1593–1599 10.1126/science.275.5306.1593
    1. Shamir R. R., Zaidel A., Joskowicz L., Bergman H., Israel Z. (2012). Microelectrode recording duration and spatial density constraints for automatic targeting of the subthalamic nucleus. Stereotact. Funct. Neurosurg. 90, 325–334 10.1159/000338252
    1. Temel Y., Kessels A., Tan S., Topdag A., Boon P., Visser-Vandewalle V. (2006). Behavioural changes after bilateral subthalamic stimulation in advanced Parkinson disease: a systematic review. Parkinsonism Relat. Disord. 12, 265–272 10.1016/j.parkreldis.2006.01.004
    1. Theodosopoulos P. V., Marks W. J., Christine C., Starr P. A. (2003). Locations of movement-related cells in the human subthalamic nucleus in Parkinson's disease. Move. Disord 18, 791–798 10.1002/mds.10446
    1. Tomer R., Aharon-Peretz J. (2004). Novelty seeking and harm avoidance in Parkinson's disease: effects of asymmetric dopamine deficiency. J. Neurol. Neurosurg. Psychiatry 75, 972–975 10.1136/jnnp.2003.024885
    1. Ventura M. I., Baynes K., Sigvardt K. A., Unruh A. M., Acklin S. S., Kirsch H. E., et al. (2012). Hemispheric asymmetries and prosodic emotion recognition deficits in Parkinson's disease. Neuropsychologia 50, 1936–1945 10.1016/j.neuropsychologia.2012.04.018
    1. Vicente S., Biseul I., Péron J., Philippot P., Drapier S., Drapier D., et al. (2009). Subthalamic nucleus stimulation affects subjective emotional experience in Parkinson's disease patients. Neuropsychologia 47, 1928–1937 10.1016/j.neuropsychologia.2009.03.003
    1. Weaver F. M., Follett K., Stern M., Hur K., Harris C., Marks W. J., et al. (2009). Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA 301, 63–73 10.1001/jama.2008.929
    1. Weise L. M., Seifried C., Eibach S., Gasser T., Roeper J., Seifert V., et al. (2013). Correlation of active contact positions with the electrophysiological and anatomical subdivisions of the subthalamic nucleus in deep brain stimulation. Stereotact. Funct. Neurosurg. 91, 298–305 10.1159/000345259
    1. Wichmann T., Bergman H., DeLong M. R. (1994). The primate subthalamic nucleus. I. Functional properties in intact animals. J. Neurophysiol. 72, 494–506
    1. Witt K., Daniels C., Reiff J., Krack P., Volkmann J., Pinsker M. O., et al. (2008). Neuropsychological and psychiatric changes after deep brain stimulation for Parkinson's disease: a randomised, multicentre study. Lancet Neurol. 7, 605–614 10.1016/S1474-4422(08)70114-5
    1. Zaidel A., Spivak A., Grieb B., Bergman H., Israel Z. (2010). Subthalamic span of beta oscillations predicts deep brain stimulation efficacy for patients with Parkinson's disease. Brain 133, 2007–2021 10.1093/brain/awq144
    1. Zaidel A., Spivak A., Shpigelman L., Bergman H., Israel Z. (2009). Delimiting subterritories of the human subthalamic nucleus by means of microelectrode recordings and a Hidden Markov Model. Move. Disord. 24, 1785–1793 10.1002/mds.22674

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera