Low-threshold calcium spike bursts in the human thalamus. Common physiopathology for sensory, motor and limbic positive symptoms

Abstract

Positive symptoms arise after lesions of the nervous system. They include neurogenic pain, tinnitus, abnormal movements, epilepsy and certain neuropsychiatric disorders. Stereotactic medial thalamotomies were performed on 104 patients with chronic therapy-resistant positive symptoms. Peroperative recordings of 2012 single units revealed an overwhelming unresponsiveness (99%) to sensory stimuli or motor activation. Among these unresponsive cells, 45.1% presented a rhythmic or random bursting activity. Rhythmic bursting activities had an average interburst interval of 263 +/- 46 ms corresponding to a frequency of 3.8 +/- 0.7 Hz. Frequency variations among the different symptoms were not statistically different. Intraburst characteristics such as the highest frequency encountered in the burst (480 +/- 80 Hz) or the mean frequency of the burst (206 +/- 44 Hz) were also similar in all patients. All bursts, rhythmic or random, fulfilled the extracellular criteria of low-threshold calcium spike (LTS) bursts. After medial thalamotomy and depending on the symptom, 43-67% of the patients reached a 50-100% relief, with sparing of all neurological functions. On the basis of these electrophysiological and clinical results, we propose a unified concept for all positive symptoms centred on a self-perpetuating thalamic cell membrane hyperpolarization, similar to the one seen in slow-wave sleep.