title: Neurobiological background for performing surgical intervention in the inferior thalamic peduncle for treatment of major depression disorders.
abstract: OBJECTIVE
  To present a review of evidence for an inhibitory thalamo-orbitofrontal system related to physiopathology of major depression disorders (MDDs) and to postulate that interfering with hyperactivity of the thalamo-orbitofrontal system by means of chronic high-frequency electrical stimulation of its main fiber connection, the inferior thalamic peduncle (ITP), may result in an improvement in patients with MDD.
  
  
  METHODS
  Experimentally, the thalamo-orbitofrontal system has been proposed as part of the nonspecific thalamic system. Under normal conditions, the nonspecific thalamic system induces characteristic electrocortical synchronization in the form of recruiting responses that mimic some sleep stages. It also inhibits input of irrelevant sensory stimuli, thus facilitating the process of selective attention. Permanent disruption of the system, via lesioning or temporary inactivation through cooling of the ITP with cryoprobes, results in a state of hyperkinesia, increased attention, and cortical desynchronization.
  
  
  RESULTS
  Surgical lesioning of the medial part of orbitofrontal cortex and white matter overlying area 13, which includes the ITP, may result in significant improvement in MDD. Imaging studies (functional magnetic resonance imaging and positron emission tomography) consistently demonstrate hyperactivity in the orbitofrontal cortex and midline thalamic regions during episodes of MDD. This hyperactivity decreases with efficient control of MDD by medical treatment, indicating that orbitofrontal cortex and midline thalamic overactivity are related to the depressive condition. Conversely, noradrenergic and serotoninergic systems in the frontal lobes have been implicated in the pathophysiology of MDD. Although noradrenergic receptor density in the frontal lobe is consistently increased in depressed patients who commit suicide, 5-hydroxytryptamine reuptake blockers, which are potent antidepressive drugs, decrease hypermetabolism in the orbital frontal cortex in MDD. Therefore, the serotonin hypothesis for depression postulates that norepinephrine and serotonin in the frontal lobes are required to maintain antidepressive responsiveness. Dysregulation of the secretion of both neurotransmitters initiates overactivity of orbitofrontal cortex, resulting in depression. It is possible that surgical interventions in this region, including electrical stimulation of ITP, disrupt adrenergic and serotoninergic dysregulation in patients with MDD.
  
  
  CONCLUSIONS
  Circumscribed lesions or electrical stimulation of the ITP, a discrete target easily identified by electrophysiological studies, may improve MDD. Electrical stimulation may have the advantage of being less invasive and more adjustable to patient needs.
authors.affiliation: Unit for Stereotactic, Functional Neurosurgery and Radiosurgery, General Hospital of Mexico, Mexico City, Mexico. slanfe@prodigy.net.mx
authors.forename: Francisco
authors.initials: F
authors.lastname: Velasco
authors.forename: Marcos
authors.initials: M
authors.lastname: Velasco
authors.forename: Fiacro
authors.initials: F
authors.lastname: Jiménez
authors.forename: Ana Luisa
authors.initials: AL
authors.lastname: Velasco
authors.forename: Rafael
authors.initials: R
authors.lastname: Salin-Pascual
mesh_terms: D000818:Animals; D003865:Major Depressive Disorder / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008959:Models, Neurological; D009434:Neural Pathways / Q000473:pathology* / Q000601:surgery; D009446:Neurobiology; D019635:Neurosurgical Procedures / Q000379:methods*; D018377:Neurotransmitter Agents / Q000378:metabolism; D013788:Thalamus / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*
chemical_list: D018377:Neurotransmitter Agents