Neuropsychiatric thalamocortical dysrhythmia: surgical implications

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 protracted 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 oversynchronization. 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.

Quantitative electroencephalography as a biomarker for proneness toward developing psychosis

“…These results, using the average signal of many EEG electrodes from schizotypal individuals, resemble the results reported using the average signal of many MEG sensors from clinical SZ individuals Jeanmonod et al, 2003;Llinas and Ribary, 2001;Llinás et al, 2001;Llinas et al, 1999;Sarnthein et al, 2003) and the interpretation is that there exists a slight, but widespread, perturbation of thalamocortical resonance (TCD) in individuals who exhibit the cluster of personality traits associated with schizotypy.…”

“…In particular, our group of HiS individuals 1) locked the thalamocortical loop in the low-α band at a lower-frequency oscillation, as measured with individual BRF; 2) displayed an abnormally high level of neural synchronisation in the same low-frequency rhythm, indicated by increased relative EEG power; and, 3) the high-α band was found to be positively correlated with both the high-β and low-γ bands. Overall, these abnormalities in cortical oscillations resemble a mild version of TCD, which has been associated with the pathophysiology of various neuropsychiatric disorders including SZ and psychosis Jeanmonod et al, 2003;Llinas et al, 1999;Schulman et al, 2011).…”

“…Dysfunctional neural activities have been studied using single unit recording from the human thalamus (Jeanmonod et al, 1996;Jeanmonod et al, 2003;Jeanmonod, 2007, 2008;Sarnthein et al, 2003Sarnthein et al, , 2005, while abnormal oscillatory activities have been assessed with magnetoencephalographic (MEG) Jeanmonod et al, 2003;Llinas and Ribary, 2001;Llinás et al, 2001;Llinas et al, 2005;Llinas et al, 1999;Schulman et al, 2011;Schulman et al, 2001) and EEG Jeanmonod, 2007, 2008;Sarnthein et al, 2003Sarnthein et al, , 2005 recordings in patients suffering from SZ, chronic psychosis, Parkinson's disease, epilepsy, neuropathic pain, tinnitus, major depression, obsessivecompulsive, affective and impulse control disorders. These studies tested the hypothesis that the pathophysiological mechanism involved in the manifestation of symptoms in these disorders is the existence of abnormal, localized and protracted low-frequency spontaneous recurrent activation of the thalamocortical system.…”

“…With TCD, low-threshold calcium spike (LTS) bursts in the thalamus have an inter-burst frequency of ~ 4 Hz in awake resting-state patients (Jeanmonod et al, 1996;Jeanmonod et al, 2003;Llinas and Steriade, 2006). This in turn exerts an increased neural synchronisation at the ~ 4 Hz frequency in thalamo-cortical modules which can be measured with EEG Jeanmonod, 2007, 2008) and MEG (Llinas et al, 1999).…”

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders – First Revision

“…In severe OCD cases, where all other available therapeutic approaches have been tried without success, neurosurgery may be a treatment option. Only unblinded studies are available that showed improvements after Á bilateral anterior capsulotomy (Lippitz et al 1999; Ló pez Ibor and Ló pez-Ibor Aliñ o 1975; Mindus et al 1990Mindus et al , 1999Oliver et al 2003;Rü ck, 2006;Skoog and Skoog 1999), Á cingulotomy (Baer et al 1995;Dougherty et al 2002;Jenike et al 1991a;Kim et al 2003;Richter et al 2004), Á limbic leucotomy (Cumming et al 1995;Hay et al 1993;Montoya et al 2002;Sachdev and Hay 1995), Á subcaudate tractotomy (Hodgkiss et al 1995;Woerdeman et al 2006) or Á thalamotomy/pallidotomy (Jeanmonod et al 2003).…”