The Impact of Mirth‐Inducing Ventral Striatal Deep Brain Stimulation on Functional and Effective Connectivity

Abstract Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is an investigational therapy for treatment‐resistant obsessive‐compulsive disorder. The ability of VC/VS DBS to evoke spontaneous mirth in patients, often accompanied by smiling and laughter, is clinically well documented. However, the neural correlates of DBS‐evoked mirth remain poorly characterized. Patients undergoing VC/VS DBS surgery underwent intraoperative evaluation in which mirth‐inducing and non‐mirth‐inducing stimulation localizations were identified. Using dynamic causal modeling (DCM) for fMRI, the effect of mirth‐inducing DBS on functional and effective connectivity among established nodes in limbic cortico‐striato‐thalamo‐cortical (CSTC) circuitry was investigated. Both mirth‐inducing and non‐mirth‐inducing VC/VS DBS consistently resulted (conjunction, global null, family‐wise error‐corrected P < 0.05) in activation of amygdala, ventral striatum, and mediodorsal thalamus. However, only mirth‐inducing DBS resulted in functional inhibition of anterior cingulate cortex. Dynamic causal modeling revealed that mirth‐inducing DBS enhanced effective connectivity from anterior cingulate to ventral striatum, while attenuating connectivity from thalamus to ventral striatum relative to non‐mirth‐inducing stimulation. These results suggest that DBS‐evoked mood elevation is accompanied by distinct patterns of limbic thalamocortical connectivity. Using the novel combination of DBS‐evoked mood alteration and functional MRI in human subjects, we provide new insights into the network‐level mechanisms that influence affect.

[1]  Ajay B. Satpute,et al.  The Brain Basis of Positive and Negative Affect: Evidence from a Meta-Analysis of the Human Neuroimaging Literature. , 2016, Cerebral cortex.

[2]  G. Rizzolatti,et al.  Mirth and laughter elicited by electrical stimulation of the human anterior cingulate cortex , 2015, Cortex.

[3]  J. Felmlee,et al.  Motor and Nonmotor Circuitry Activation Induced by Subthalamic Nucleus Deep Brain Stimulation in Patients With Parkinson Disease: Intraoperative Functional Magnetic Resonance Imaging for Deep Brain Stimulation. , 2015, Mayo Clinic proceedings.

[4]  K. Berridge,et al.  Pleasure Systems in the Brain , 2015, Neuron.

[5]  H. Fukuyama,et al.  Neural correlates of mirth and laughter: A direct electrical cortical stimulation study , 2015, Cortex.

[6]  Jason Tucciarone,et al.  The Mediodorsal Thalamus Drives Feedforward Inhibition in the Anterior Cingulate Cortex via Parvalbumin Interneurons , 2015, The Journal of Neuroscience.

[7]  Jens Kuhn,et al.  Deep brain stimulation for treatment-refractory obsessive compulsive disorder: a systematic review , 2014, BMC Psychiatry.

[8]  Erika K. Ross,et al.  Subthalamic Nucleus Deep Brain Stimulation Induces Motor Network BOLD Activation: Use of a High Precision MRI Guided Stereotactic System for Nonhuman Primates , 2014, Brain Stimulation.

[9]  Thomas H. B. FitzGerald,et al.  Interoceptive inference: homeostasis and decision-making , 2014, Trends in Cognitive Sciences.

[10]  Karl J. Friston,et al.  Resting state functional MRI in Parkinson’s disease: the impact of deep brain stimulation on ‘effective’ connectivity , 2014, Brain : a journal of neurology.

[11]  M. Frye,et al.  Centromedian-Parafascicular Deep Brain Stimulation Induces Differential Functional Inhibition of the Motor, Associative, and Limbic Circuits in Large Animals , 2013, Biological Psychiatry.

[12]  E. Benarroch,et al.  Anterior nucleus of the thalamus , 2013, Neurology.

[13]  A. Seth.  Interoceptive inference, emotion, and the embodied self , 2013, Trends in Cognitive Sciences.

[14]  Anna S. Mitchell,et al.  What does the mediodorsal thalamus do? , 2013, Front. Syst. Neurosci..

[15]  B. Mädler,et al.  Rapid Effects of Deep Brain Stimulation for Treatment-Resistant Major Depression , 2013, Biological Psychiatry.

[16]  Matt A. Bernstein,et al.  Measurements of RF heating during 3.0-T MRI of a pig implanted with deep brain stimulator. , 2013, Magnetic resonance imaging.

[17]  Elise Wattendorf,et al.  Exploration of the neural correlates of ticklish laughter by functional magnetic resonance imaging. , 2013, Cerebral cortex.

[18]  Ajay B. Satpute,et al.  Large-scale brain networks in affective and social neuroscience: towards an integrative functional architecture of the brain , 2013, Current Opinion in Neurobiology.

[19]  M. Vink,et al.  Deep brain stimulation restores frontostriatal network activity in obsessive-compulsive disorder , 2013, Nature Neuroscience.

[20]  Karl J. Friston,et al.  Therapeutic Subthalamic Nucleus Deep Brain Stimulation Reverses Cortico-Thalamic Coupling during Voluntary Movements in Parkinson's Disease , 2012, PloS one.

[21]  Hoon-Ki Min,et al.  Deep brain stimulation induces BOLD activation in motor and non-motor networks: An fMRI comparison study of STN and EN/GPi DBS in large animals , 2012, NeuroImage.

[22]  V. Sturm,et al.  Long-Term Effects of Nucleus Accumbens Deep Brain Stimulation in Treatment-Resistant Depression: Evidence for Sustained Efficacy , 2012, Neuropsychopharmacology.

[23]  C. McIntyre,et al.  Axonal pathways linked to therapeutic and nontherapeutic outcomes during psychiatric deep brain stimulation , 2012, Human brain mapping.

[24]  Lars Nyberg,et al.  Pleasant human touch is represented in pregenual anterior cingulate cortex , 2012, NeuroImage.

[25]  Karl J. Friston,et al.  Generalised filtering and stochastic DCM for fMRI , 2011, NeuroImage.

[26]  Jesús Pujol,et al.  Enhanced brain responsiveness during active emotional face processing in obsessive compulsive disorder , 2011, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[27]  Suzanne N Haber,et al.  Rules Ventral Prefrontal Cortical Axons Use to Reach Their Targets: Implications for Diffusion Tensor Imaging Tractography and Deep Brain Stimulation for Psychiatric Illness , 2011, The Journal of Neuroscience.

[28]  Vittorio Gallese,et al.  Emotional and Social Behaviors Elicited by Electrical Stimulation of the Insula in the Macaque Monkey , 2011, Current Biology.

[29]  D. Bowers,et al.  Smile and laughter induction and intraoperative predictors of response to deep brain stimulation for obsessive-compulsive disorder , 2011, NeuroImage.

[30]  D. Perani,et al.  clinical/metabolic correlation study after treatment (18F)FDG PET study in obsessive-compulsive disorder. A , 2011 .

[31]  G. Wagner,et al.  Fronto‐cingulate effective connectivity in obsessive compulsive disorder: A study with fMRI and dynamic causal modeling , 2010, Human brain mapping.

[32]  S. E. Stewart,et al.  Amygdala activation in response to facial expressions in pediatric obsessive–compulsive disorder , 2010, Depression and anxiety.

[33]  Michael X. Cohen,et al.  Nucleus Accumbens Deep Brain Stimulation Decreases Ratings of Depression and Anxiety in Treatment-Resistant Depression , 2010, Biological Psychiatry.

[34]  P. Fox,et al.  Metaanalytic connectivity modeling: Delineating the functional connectivity of the human amygdala , 2009, Human brain mapping.

[35]  G. Friehs,et al.  Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience , 2010, Molecular Psychiatry.

[36]  K. Berridge,et al.  Towards a functional neuroanatomy of pleasure and happiness , 2009, Trends in Cognitive Sciences.

[37]  Karl J. Friston,et al.  Bayesian model selection for group studies , 2009, NeuroImage.

[38]  A. Grace,et al.  Nucleus Accumbens Deep Brain Stimulation Produces Region-Specific Alterations in Local Field Potential Oscillations and Evoked Responses In Vivo , 2009, The Journal of Neuroscience.

[39]  A. Wohlschläger,et al.  The link between facial feedback and neural activity within central circuitries of emotion--new insights from botulinum toxin-induced denervation of frown muscles. , 2009, Cerebral cortex.

[40]  A. Craig,et al.  How do you feel — now? The anterior insula and human awareness , 2009, Nature Reviews Neuroscience.

[41]  E. Benarroch.  The midline and intralaminar thalamic nuclei , 2008, Neurology.

[42]  Helen Barbas,et al.  Sequence of information processing for emotions through pathways linking temporal and insular cortices with the amygdala , 2008, NeuroImage.

[43]  P. Boesiger,et al.  GABA concentrations in the human anterior cingulate cortex predict negative BOLD responses in fMRI , 2007, Nature Neuroscience.

[44]  A. Grace,et al.  High-Frequency Deep Brain Stimulation of the Nucleus Accumbens Region Suppresses Neuronal Activity and Selectively Modulates Afferent Drive in Rat Orbitofrontal Cortex In Vivo , 2007, The Journal of Neuroscience.

[45]  C. Keysers,et al.  Facial expressions: What the mirror neuron system can and cannot tell us , 2007, Social neuroscience.

[46]  Brian N. Pasley,et al.  Analysis of oxygen metabolism implies a neural origin for the negative BOLD response in human visual cortex , 2007, NeuroImage.

[47]  D. Kleinfeld,et al.  Suppressed Neuronal Activity and Concurrent Arteriolar Vasoconstriction May Explain Negative Blood Oxygenation Level-Dependent Signal , 2007, The Journal of Neuroscience.

[48]  J. Allman,et al.  Brain activation during sight gags and language-dependent humor. , 2007, Cerebral cortex.

[49]  G. Friehs,et al.  Three-Year Outcomes in Deep Brain Stimulation for Highly Resistant Obsessive–Compulsive Disorder , 2006, Neuropsychopharmacology.

[50]  Michael S Okun,et al.  Deep brain stimulation in the internal capsule and nucleus accumbens region: responses observed during active and sham programming , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[51]  Pietro Pietrini,et al.  Neurocircuitry of disgust and anxiety in obsessive-compulsive disorder: A positron emission tomography study , 2006, Metabolic Brain Disease.

[52]  F. Woermann,et al.  Laughter and the mesial and lateral premotor cortex , 2006, Epilepsy & Behavior.

[53]  N. Logothetis,et al.  Negative functional MRI response correlates with decreases in neuronal activity in monkey visual area V1 , 2006, Nature Neuroscience.

[54]  L. Spinelli,et al.  Contralateral Smile and Laughter, but No Mirth, Induced by Electrical Stimulation of the Cingulate Cortex , 2006, Epilepsia.

[55]  Peter Erhard,et al.  A common neural basis for receptive and expressive communication of pleasant facial affect , 2005, NeuroImage.

[56]  S. Taylor,et al.  Deep brain stimulation for refractory obsessive-compulsive disorder , 2005, Biological Psychiatry.

[57]  Kent A. Kiehl,et al.  Dysfunctional Action Monitoring Hyperactivates Frontal–striatal Circuits in Obsessive–compulsive Disorder: an Event-related Fmri Study , 2004 .

[58]  S. Rauch,et al.  Amygdala responses to human faces in obsessive-compulsive disorder , 2004, Biological Psychiatry.

[59]  Joseph E LeDoux,et al.  Extinction Learning in Humans Role of the Amygdala and vmPFC , 2004, Neuron.

[60]  Karl J. Friston,et al.  Comparing dynamic causal models , 2004, NeuroImage.

[61]  M. Phillips,et al.  Distinct neural correlates of washing, checking, and hoarding symptom dimensions in obsessive-compulsive disorder. , 2004, Archives of general psychiatry.

[62]  C. McIntyre,et al.  Uncovering the mechanism(s) of action of deep brain stimulation: activation, inhibition, or both , 2004, Clinical Neurophysiology.

[63]  Scott T Grafton,et al.  Functional imaging of face and hand imitation: towards a motor theory of empathy , 2004, NeuroImage.

[64]  P. Strick,et al.  Macro-architecture of basal ganglia loops with the cerebral cortex: use of rabies virus to reveal multisynaptic circuits. , 2004, Progress in brain research.

[65]  M. Greicius,et al.  Humor Modulates the Mesolimbic Reward Centers , 2003, Neuron.

[66]  Karl J. Friston,et al.  Dynamic causal modelling , 2003, NeuroImage.

[67]  Steven Laureys,et al.  How valid is the clinical diagnosis of Parkinson ’ s disease in the community ? , 2022 .

[68]  A. Shmuel,et al.  Sustained Negative BOLD, Blood Flow and Oxygen Consumption Response and Its Coupling to the Positive Response in the Human Brain , 2002, Neuron.

[69]  C. Carter,et al.  The anterior cingulate as a conflict monitor: fMRI and ERP studies , 2002, Physiology & Behavior.

[70]  P. O’Donnell,et al.  Timing-dependent limbic-motor synaptic integration in the nucleus accumbens , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[71]  P. Petrovic,et al.  Placebo and Opioid Analgesia-- Imaging a Shared Neuronal Network , 2002, Science.

[72]  S. Rauch,et al.  Prospective long-term follow-up of 44 patients who received cingulotomy for treatment-refractory obsessive-compulsive disorder. , 2002, The American journal of psychiatry.

[73]  Nikolaus R. McFarland,et al.  The Place of the Thalamus in Frontal Cortical-Basal Ganglia Circuits , 2001, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[74]  James L. Herrick,et al.  Cortical innervation of the facial nucleus in the non-human primate: a new interpretation of the effects of stroke and related subtotal brain trauma on the muscles of facial expression. , 2001, Brain : a journal of neurology.

[75]  R. Knight,et al.  Prefrontal–cingulate interactions in action monitoring , 2000, Nature Neuroscience.

[76]  Karl J. Friston,et al.  Multisubject fMRI Studies and Conjunction Analyses , 1999, NeuroImage.

[77]  Karl J. Friston,et al.  Brain systems mediating aversive conditioning: An event related fMRI study , 1998, NeuroImage.

[78]  Karl J. Friston,et al.  Brain Systems Mediating Aversive Conditioning: an Event-Related fMRI Study , 1998, Neuron.

[79]  M. Botvinick,et al.  Anterior cingulate cortex, error detection, and the online monitoring of performance. , 1998, Science.

[80]  Charles L. Wilson,et al.  Electric current stimulates laughter , 1998, Nature.

[81]  J. R. Baker,et al.  Functional magnetic resonance imaging of symptom provocation in obsessive-compulsive disorder. , 1996, Archives of general psychiatry.

[82]  H. Groenewegen,et al.  The nucleus accumbens: gateway for limbic structures to reach the motor system? , 1996, Progress in brain research.

[83]  F Fazio,et al.  [18F]FDG PET Study in Obsessive–Compulsive Disorder , 1995, British Journal of Psychiatry.

[84]  S. Haber,et al.  Primate cingulostriatal projection: Limbic striatal versus sensorimotor striatal input , 1994, The Journal of comparative neurology.

[85]  R P Lesser,et al.  Mirth, laughter and gelastic seizures. , 1993, Brain : a journal of neurology.

[86]  A. Parent,et al.  Efferent connections of the centromedian and parafascicular thalamic nuclei in the squirrel monkey: A PHA‐L study of subcortical projections , 1992, The Journal of comparative neurology.

[87]  F. Strack,et al.  Inhibiting and facilitating conditions of the human smile: a nonobtrusive test of the facial feedback hypothesis. , 1988, Journal of personality and social psychology.

[88]  G. E. Alexander,et al.  Parallel organization of functionally segregated circuits linking basal ganglia and cortex. , 1986, Annual review of neuroscience.

[89]  P. Goldman-Rakic,et al.  Brainstem innervation of prefrontal and anterior cingulate cortex in the rhesus monkey revealed by retrograde transport of HRP , 1982, The Journal of comparative neurology.