Thalamus & Related Systems 2 (2003) 103–113 Neuropsychiatric thalamocortical dysrhythmia: surgical implications D. Jeanmonod a,∗ , J. Schulman b , R. Ramirez b , R. Cancro c , M. Lanz d , A. Morel a , M. Magnin a , M. Siegemund a , E. Kronberg b , U. Ribary b , R. Llinas b,1 a Laboratory for Functional Neurosurgery, Neurosurgical Clinic, University Hospital, Zurich, Switzerland b Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY, USA c Department of Psychiatry, New York University School of Medicine, New York, NY, USA d Psychiatry Center Hard, Zurich, Switzerland Accepted 22 November 2002 Abstract Neuropsychiatric surgery has had a long and complex history with examples of less than optimal surgical procedures implemented in wrong settings. Such past errors have raised important philosophical and ethical issues that remain with us for good reasons. However, the existence of enormous suffering due to chronic therapy-resistant disabling neuropsychiatric disorders compels a search for alternative surgical approaches based on a sound understanding of the underlying physiopathological mechanisms. We bring evidence, from single cell physiology and magnetoencephalography, for the existence of a set of neuropsychiatric disorders characterized by localized and pro- tracted low frequency spontaneous recurrent activation of the thalamocortical system. This condition, labeled thalamocortical dysrhythmia, underlies certain chronic psychotic, affective, obsessive compulsive, anxiety and impulse control disorders. Considering the central role of recurrent oscillatory thalamocortical properties in the generation of normal hemispheric functions, we propose a surgical approach that provides a reestablishment of normal thalamocortical oscillations without reduction of cortical tissue and its specific thalamic connectivity. It consists of small strategically placed pallidal and medial thalamic lesions that serve to make subcritical the increased low frequency thalamocortical recurrent network activity. This result is attained via reduction of both thalamic overinhibition and low frequency over- synchronization. Thalamic disinhibition is obtained by a lesion in the anterior medial paralimbic pallidum. The medial thalamic lesion is localized in the posterior part of the central lateral nucleus, where a large majority of cells have been shown to be locked in low frequency production and to have lost their normal activation patterns. We present here our experience with 11 patients, including clinical follow ups and pre- and postsurgical magnetoencephalographic studies. The evidence speaks (1) for a benign and efficient surgical approach, and (2) for the relevance of the patient’s presurgical cognitive and social settings, making them more or less prone to postoperative psychoreactive manifestations upon rekindling of personal goals and social reentry. © 2003 Elsevier Science Ltd. All rights reserved. Keywords: Low threshold calcium spike bursts; Obsessive compulsive disorder; Psychosis; Anterior medial pallidotomy; Central lateral thalamotomy 1. Introduction After the questionable and inordinately wide application of the prefrontal lobotomy (Moniz, 1936; Freeman, 1948) in the first half of the twentieth century, many groups real- ized the necessity of confining surgical interventions to the paralimbic (or mesocortical) domain (Mesulam, 1985). This gave rise to the three main stereotactic operations still in use today in view of their efficiency and limited side effects: (1) ∗ Corresponding author. Sternwartstrasse 6, 8091 Zurich, Switzerland. Tel.: +41-1-2552684; fax: +41-1-2558946. E-mail addresses: daniel.jeanmonod@usz.ch (D. Jeanmonod), llinar01@endeavor.med.nyu.edu (R. Llinas). 1 Co-corresponding author. Present address: 550 First Avenue MSB-442, New York, NY 10016, USA. Tel.: +1-212-263-5415; fax: +1-212-689-9060. the anterior cingulotomy (Ballantine et al., 1977), (2) the subcaudate tractotomy (Knight, 1973) and (3) the anterior capsulotomy (Bingley et al., 1973). These three procedures entail an interruption of the thalamocortical paralimbic frontal network. Such surgical approaches have been effi- cient against major depression and obsessive compulsive dis- order (OCD), but not against psychosis. Very early however, Spiegel and Wycis (1952/1962) had explored the possibili- ties of stereotactic interventions in the mediodorsal nucleus of the thalamus and described positive results in psychotic patients. There are both older and more recent data demonstrating a physiopathological and histological involvement of paralim- bic cortical areas and their corresponding specific thalamic partner, the mediodorsal nucleus, in the generation of the neuropsychiatric disorders. Indeed, electroencephalographic 1472-9288/03/$ – see front matter © 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S1472-9288(03)00010-4