Both animal studies and studies using deep brain stimulation in humans have demonstrated the involvement of the subthalamic nucleus (STN) in motivational and emotional processes; however, participation of this nucleus in processing human emotion has not been investigated directly at the single-neuron level. We analyzed the relationship between the neuronal firing from intraoperative microrecordings from the STN during affective picture presentation in patients with Parkinson's disease (PD) and the affective ratings of emotional valence and arousal performed subsequently. We observed that 17% of neurons responded to emotional valence and arousal of visual stimuli according to individual ratings. The activity of some neurons was related to emotional valence, whereas different neurons responded to arousal. In addition, 14% of neurons responded to visual stimuli. Our results suggest the existence of neurons involved in processing or transmission of visual and emotional information in the human STN, and provide evidence of separate processing of the affective dimensions of valence and arousal at the level of single neurons as well.

Department of Cybernetics Faculty of Electrical Engineering Czech Technical University Prague 166 27 Prague Czech Republic; and

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine and General University Hospital Charles University Prague 128 21 Prague Czech Republic;

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine and General University Hospital Charles University Prague 128 21 Prague Czech Republic; Department of Cybernetics Faculty of Electrical Engineering Czech Technical University Prague 166 27 Prague Czech Republic; and

Department of Stereotactic and Radiation Neurosurgery Na Homolce Hospital 150 30 Prague Czech Republic

See more in PubMed

Okun MS. Deep-brain stimulation for Parkinson’s disease. N Engl J Med. 2012;367(16):1529–1538. PubMed

Alexander GE, Crutcher MD, DeLong MR. Basal ganglia-thalamocortical circuits: Parallel substrates for motor, oculomotor, “prefrontal” and “limbic” functions. Prog Brain Res. 1990;85:119–146. PubMed

Voon V, Kubu C, Krack P, Houeto JL, Tröster AI. Deep brain stimulation: Neuropsychological and neuropsychiatric issues. Mov Disord. 2006;21(Suppl 14):S305–S327. PubMed

Castrioto A, Lhommée E, Moro E, Krack P. Mood and behavioural effects of subthalamic stimulation in Parkinson’s disease. Lancet Neurol. 2014;13(3):287–305. PubMed

Dujardin K, et al. Subthalamic nucleus stimulation induces deficits in decoding emotional facial expressions in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2004;75(2):202–208. PubMed PMC

Schneider F, et al. Deep brain stimulation of the subthalamic nucleus enhances emotional processing in Parkinson disease. Arch Gen Psychiatry. 2003;60(3):296–302. PubMed

Kühn AA, et al. Activation of the subthalamic region during emotional processing in Parkinson disease. Neurology. 2005;65(5):707–713. PubMed

Schroeder U, et al. Facial expression recognition and subthalamic nucleus stimulation. J Neurol Neurosurg Psychiatry. 2004;75(4):648–650. PubMed PMC

Baunez C, Amalric M, Robbins TW. Enhanced food-related motivation after bilateral lesions of the subthalamic nucleus. J Neurosci. 2002;22(2):562–568. PubMed PMC

Rouaud T, et al. Reducing the desire for cocaine with subthalamic nucleus deep brain stimulation. Proc Natl Acad Sci USA. 2010;107(3):1196–1200. PubMed PMC

Serranová T, et al. Subthalamic nucleus stimulation affects incentive salience attribution in Parkinson’s disease. Mov Disord. 2011;26(12):2260–2266. PubMed

Serranová T, et al. Sex, food and threat: Startling changes after subthalamic stimulation in Parkinson's disease. Brain Stimul. 2013;6(5):740–745. PubMed

Karama S, Armony J, Beauregard M. Film excerpts shown to specifically elicit various affects lead to overlapping activation foci in a large set of symmetrical brain regions in males. PLoS ONE. 2011;6(7):e22343. PubMed PMC

Frühholz S, Grandjean D. Towards a fronto-temporal neural network for the decoding of angry vocal expressions. Neuroimage. 2012;62(3):1658–1666. PubMed

Kawasaki H, et al. Analysis of single-unit responses to emotional scenes in human ventromedial prefrontal cortex. J Cogn Neurosci. 2005;17(10):1509–1518. PubMed

Laxton AW, et al. Neuronal coding of implicit emotion categories in the subcallosal cortex in patients with depression. Biol Psychiatry. 2013;74(10):714–719. PubMed

Ojemann JG, Ojemann GA, Lettich E. Neuronal activity related to faces and matching in human right nondominant temporal cortex. Brain. 1992;115(Pt 1):1–13. PubMed

Wang S, et al. Neurons in the human amygdala selective for perceived emotion. Proc Natl Acad Sci USA. 2014;111(30):E3110–E3119. PubMed PMC

Russell JA. Core affect and the psychological construction of emotion. Psychol Rev. 2003;110(1):145–172. PubMed

Lang PJ, Bradley MM, Cuthbert BN. Emotion, motivation, and anxiety: Brain mechanisms and psychophysiology. Biol Psychiatry. 1998;44(12):1248–1263. PubMed

Lang PJ, Greenwald MK, Bradley MM, Hamm AO. Looking at pictures: Affective, facial, visceral, and behavioral reactions. Psychophysiology. 1993;30(3):261–273. PubMed

Hamann S, Canli T. Individual differences in emotion processing. Curr Opin Neurobiol. 2004;14(2):233–238. PubMed

Degos B, Deniau JM, Chavez M, Maurice N. Chronic but not acute dopaminergic transmission interruption promotes a progressive increase in cortical beta frequency synchronization: Relationships to vigilance state and akinesia. Cereb Cortex. 2009;19(7):1616–1630. PubMed

Bergman H, Wichmann T, Karmon B, DeLong MR. The primate subthalamic nucleus, II: Neuronal activity in the MPTP model of parkinsonism. J Neurophysiol. 1994;72(2):507–520. PubMed

Jenkinson N, Brown P. New insights into the relationship between dopamine, beta oscillations and motor function. Trends Neurosci. 2011;34(12):611–618. PubMed

Huebl J, et al. Oscillatory subthalamic nucleus activity is modulated by dopamine during emotional processing in Parkinson’s disease. Cortex. 2014;60:69–81. PubMed

Brown P, Williams D. Basal ganglia local field potential activity: Character and functional significance in the human. Clin Neurophysiol. 2005;116(11):2510–2519. PubMed

Brücke C, et al. The subthalamic region is activated during valence-related emotional processing in patients with Parkinson’s disease. Eur J Neurosci. 2007;26(3):767–774. PubMed

Huebl J, et al. Modulation of subthalamic alpha activity to emotional stimuli correlates with depressive symptoms in Parkinson’s disease. Mov Disord. 2011;26(3):477–483. PubMed

Morel A. Stereotactic Atlas of the Human Thalamus and Basal Ganglia. Informa Healthcare; London: 2007. p. 160.

Bradley MM, Codispoti M, Lang PJ. A multi-process account of startle modulation during affective perception. Psychophysiology. 2006;43(5):486–497. PubMed

Adolphs R. Neural systems for recognizing emotion. Curr Opin Neurobiol. 2002;12(2):169–177. PubMed

Guillory SA, Bujarski KA. Exploring emotions using invasive methods: Review of 60 years of human intracranial electrophysiology. Soc Cogn Affect Neurosci. 2014;9(12):1880–1889. PubMed PMC

Schupp HT, Junghöfer M, Weike AI, Hamm AO. The selective processing of briefly presented affective pictures: An ERP analysis. Psychophysiology. 2004;41(3):441–449. PubMed

Junghöfer M, Bradley MM, Elbert TR, Lang PJ. Fleeting images: A new look at early emotion discrimination. Psychophysiology. 2001;38(2):175–178. PubMed

D’Hondt F, et al. Early brain-body impact of emotional arousal. Front Hum Neurosci. 2010;4:33. PubMed PMC

Burgmer M, et al. Early affective processing in patients with acute posttraumatic stress disorder: Magnetoencephalographic correlates. PLoS ONE. 2013;8(8):e71289. PubMed PMC

Cacioppo JT, Petty RE, Losch ME, Kim HS. Electromyographic activity over facial muscle regions can differentiate the valence and intensity of affective reactions. J Pers Soc Psychol. 1986;50(2):260–268. PubMed

Vrana SR, Spence EL, Lang PJ. The startle probe response: A new measure of emotion? J Abnorm Psychol. 1988;97(4):487–491. PubMed

Kuhbandner C, Zehetleitner M. Dissociable effects of valence and arousal in adaptive executive control. PLoS ONE. 2011;6(12):e29287. PubMed PMC

Faure A, Reynolds SM, Richard JM, Berridge KC. Mesolimbic dopamine in desire and dread: Enabling motivation to be generated by localized glutamate disruptions in nucleus accumbens. J Neurosci. 2008;28(28):7184–7192. PubMed PMC

Anders S, Lotze M, Erb M, Grodd W, Birbaumer N. Brain activity underlying emotional valence and arousal: A response-related fMRI study. Hum Brain Mapp. 2004;23(4):200–209. PubMed PMC

Colibazzi T, et al. Neural systems subserving valence and arousal during the experience of induced emotions. Emotion. 2010;10(3):377–389. PubMed

Small DM, et al. Dissociation of neural representation of intensity and affective valuation in human gustation. Neuron. 2003;39(4):701–711. PubMed

Anderson AK, et al. Dissociated neural representations of intensity and valence in human olfaction. Nat Neurosci. 2003;6(2):196–202. PubMed

Bradley MM, Codispoti M, Cuthbert BN, Lang PJ. Emotion and motivation I: Defensive and appetitive reactions in picture processing. Emotion. 2001;1(3):276–298. PubMed

Winston JS, Gottfried JA, Kilner JM, Dolan RJ. Integrated neural representations of odor intensity and affective valence in human amygdala. J Neurosci. 2005;25(39):8903–8907. PubMed PMC

Roy M, Shohamy D, Wager TD. Ventromedial prefrontal-subcortical systems and the generation of affective meaning. Trends Cogn Sci. 2012;16(3):147–156. PubMed PMC

Berridge KC, Kringelbach ML. Neuroscience of affect: Brain mechanisms of pleasure and displeasure. Curr Opin Neurobiol. 2013;23(3):294–303. PubMed PMC

Grabenhorst F, Rolls ET. Value, pleasure and choice in the ventral prefrontal cortex. Trends Cogn Sci. 2011;15(2):56–67. PubMed

Smith KS, Tindell AJ, Aldridge JW, Berridge KC. Ventral pallidum roles in reward and motivation. Behav Brain Res. 2009;196(2):155–167. PubMed PMC

Humphries MD, Prescott TJ. The ventral basal ganglia, a selection mechanism at the crossroads of space, strategy, and reward. Prog Neurobiol. 2010;90(4):385–417. PubMed

Haber SN, Knutson B. The reward circuit: Linking primate anatomy and human imaging. Neuropsychopharmacology. 2010;35(1):4–26. PubMed PMC

Péron J, Frühholz S, Vérin M, Grandjean D. Subthalamic nucleus: A key structure for emotional component synchronization in humans. Neurosci Biobehav Rev. 2013;37(3):358–373. PubMed

Baunez C, Yelnik J, Mallet L. Six questions on the subthalamic nucleus: Lessons from animal models and from stimulated patients. Neuroscience. 2011;198:193–204. PubMed

Haynes WI, Haber SN. 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. 2013;33(11):4804–4814. PubMed PMC

Nambu A, Tokuno H, Takada M. Functional significance of the cortico-subthalamo-pallidal “hyperdirect” pathway. Neurosci Res. 2002;43(2):111–117. PubMed

Parent A, Hazrati LN. Functional anatomy of the basal ganglia, II: The place of subthalamic nucleus and external pallidum in basal ganglia circuitry. Brain Res Brain Res Rev. 1995;20(1):128–154. PubMed

Groenewegen HJ, Berendse HW. Connections of the subthalamic nucleus with ventral striatopallidal parts of the basal ganglia in the rat. J Comp Neurol. 1990;294(4):607–622. PubMed

Winter C, et al. High-frequency stimulation of the subthalamic nucleus modulates neurotransmission in limbic brain regions of the rat. Exp Brain Res. 2008;185(3):497–507. PubMed

Turner MS, Lavin A, Grace AA, Napier TC. Regulation of limbic information outflow by the subthalamic nucleus: Excitatory amino acid projections to the ventral pallidum. J Neurosci. 2001;21(8):2820–2832. PubMed PMC

Ghashghaei HT, Hilgetag CC, Barbas H. Sequence of information processing for emotions based on the anatomic dialogue between prefrontal cortex and amygdala. Neuroimage. 2007;34(3):905–923. PubMed PMC

Lambert C, et al. Confirmation of functional zones within the human subthalamic nucleus: Patterns of connectivity and sub-parcellation using diffusion-weighted imaging. Neuroimage. 2012;60(1):83–94. PubMed PMC

Wager TD, Phan KL, Liberzon I, Taylor SF. Valence, gender, and lateralization of functional brain anatomy in emotion: A meta-analysis of findings from neuroimaging. Neuroimage. 2003;19(3):513–531. PubMed

Lindquist KA, Wager TD, Kober H, Bliss-Moreau E, Barrett LF. The brain basis of emotion: A meta-analytic review. Behav Brain Sci. 2012;35(3):121–143. PubMed PMC

Frühholz S, Grandjean D. Multiple subregions in superior temporal cortex are differentially sensitive to vocal expressions: A quantitative meta-analysis. Neurosci Biobehav Rev. 2013;37(1):24–35. PubMed

Eitan R, et al. Asymmetric right/left encoding of emotions in the human subthalamic nucleus. Front Syst Neurosci. 2013;7:69. PubMed PMC

Karachi C, et al. The pallidosubthalamic projection: An anatomical substrate for nonmotor functions of the subthalamic nucleus in primates. Mov Disord. 2005;20(2):172–180. PubMed

Joel D, Weiner I. The connections of the primate subthalamic nucleus: Indirect pathways and the open-interconnected scheme of basal ganglia-thalamocortical circuitry. Brain Res Brain Res Rev. 1997;23(1-2):62–78. PubMed

Brunenberg EJ, et al. Structural and resting state functional connectivity of the subthalamic nucleus: Identification of motor STN parts and the hyperdirect pathway. PLoS ONE. 2012;7(6):e39061. PubMed PMC

Espinosa-Parrilla JF, Baunez C, Apicella P. Linking reward processing to behavioral output: Motor and motivational integration in the primate subthalamic nucleus. Front Comput Neurosci. 2013;7:175. PubMed PMC

Matsumura M, Kojima J, Gardiner TW, Hikosaka O. Visual and oculomotor functions of monkey subthalamic nucleus. J Neurophysiol. 1992;67(6):1615–1632. PubMed

Coizet V, et al. Short-latency visual input to the subthalamic nucleus is provided by the midbrain superior colliculus. J Neurosci. 2009;29(17):5701–5709. PubMed PMC

Rolland M, Carcenac C, Overton PG, Savasta M, Coizet V. Enhanced visual responses in the superior colliculus and subthalamic nucleus in an animal model of Parkinson’s disease. Neuroscience. 2013;252:277–288. PubMed

Jech R, et al. Deep brain stimulation of the subthalamic nucleus affects resting EEG and visual evoked potentials in Parkinson’s disease. Clin Neurophysiol. 2006;117(5):1017–1028. PubMed

Shires J, Joshi S, Basso MA. Shedding new light on the role of the basal ganglia-superior colliculus pathway in eye movements. Curr Opin Neurobiol. 2010;20(6):717–725. PubMed PMC

Tamietto M, de Gelder B. Neural bases of the non-conscious perception of emotional signals. Nat Rev Neurosci. 2010;11(10):697–709. PubMed

Braak H, et al. Staging of the intracerebral inclusion body pathology associated with idiopathic Parkinson’s disease (preclinical and clinical stages) J Neurol. 2002;249(Suppl 3:):III/1–III/5. PubMed

Péron J, Dondaine T, Le Jeune F, Grandjean D, Vérin M. Emotional processing in Parkinson’s disease: A systematic review. Mov Disord. 2012;27(2):186–199. PubMed

Lang PJ, Bradley MM, Cuthbert BN. International Affective Picture System (IAPS): Affective Ratings of Pictures and Instruction Manual. University of Florida; Gainesville, FL: 2008. Technical Report A-8.

Gross RE, Krack P, Rodriguez-Oroz MC, Rezai AR, Benabid AL. Electrophysiological mapping for the implantation of deep brain stimulators for Parkinson’s disease and tremor. Mov Disord. 2006;21(Suppl 14):S259–S283. PubMed

Pollak P, et al. Intraoperative micro- and macrostimulation of the subthalamic nucleus in Parkinson’s disease. Mov Disord. 2002;17(Suppl 3):S155–S161. PubMed

Sieger T, et al. Basal ganglia neuronal activity during scanning eye movements in Parkinson’s disease. PLoS ONE. 2013;8(11):e78581. PubMed PMC

Jech R, et al. The subthalamic microlesion story in Parkinson’s disease: Electrode insertion-related motor improvement with relative cortico-subcortical hypoactivation in fMRI. PLoS ONE. 2012;7(11):e49056. PubMed PMC

Quiroga RQ, Nadasdy Z, Ben-Shaul Y. Unsupervised spike detection and sorting with wavelets and superparamagnetic clustering. Neural Comput. 2004;16(8):1661–1687. PubMed

Wild J, Prekopcsak Z, Sieger T, Novak D, Jech R. Performance comparison of extracellular spike sorting algorithms for single-channel recordings. J Neurosci Methods. 2012;203(2):369–376. PubMed

R Core Team . R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing; Vienna: 2013.

Topography of emotional valence and arousal within the motor part of the subthalamic nucleus in Parkinson's disease