Although it is widely accepted that the cortex participates in pain perception, there is no direct evidence for the existence of cortical neurons that respond to noxious or painful stimuli in humans. Anatomical and neurophysiological studies in animals as well as brain imaging and evoked potential studies in humans suggest that the anterior cingulate cortex (ACC) is an important area for processing sensory information related to pain 1-7 . We have now identified single neurons in ACC that respond selectively to painful thermal and mechanical stimuli, supporting a role for the ACC in pain perception.Cingulotomy procedures for the treatment of psychiatric disease provided a unique opportunity to examine whether neurons in the ACC of awake humans respond to painful stimuli. Single-neuron recordings and microstimulation with tungsten microelectrodes (methods previously described 8 ) were carried out in patients under local anesthesia, without analgesics or sedatives. Details of the microelectrode procedure were published previously 8 .Microelectrode exploration of the ACC was carried out in 11 patients undergoing bilateral cingulotomy for chronic depression (n = 5) or obsessive-compulsive disorder (n = 6). Four patients had the procedure repeated to enlarge lesions that produced only modneurotransmission is pivotal in the generation of cyclic firing activity in SCN neurons 10 and that melatonin acts directly at the SCN to inhibit neuronal firing 5 , enhancement of GABA A receptor function by activation of Mel 1a receptors may mediate sleep induction and regulation of mammalian circadian time-keeping by melatonin. In addition, our results suggest an important role for melatonin acting via Mel 1b receptors in hippocampal function.Previous studies linked both Mel 1a and Mel 1b receptors to inhibition of adenylyl cyclase 3,4 . However, to generate the observed differences in GABA A receptor responses, another second-messenger pathway must be involved. Further characterization of intracellular mechanisms differently affected by Mel 1a and Mel 1b may explain the diverse effects of melatonin in mammalian brain.
In late-stage Parkinson's disease, pallidotomy significantly reduces levodopa-induced dyskinesias and off-period disability. Much of the benefit is sustained at two years, although some improvements, such as those on the ipsilateral side and in axial symptoms, wane within the first year. The on-period symptoms that are resistant to dopaminergic therapy do not respond to pallidotomy.
Methods for localizing the posteroventral globus pallidus intermus are described. The authors' techniques include the use of microelectrodes to record single-unit activity and to microstimulate in human pallidum and its surrounding structures. This technique allows a precise determination of the locations of characteristic cell types in sequential trajectories through the external and internal segments of the pallidum. The location of the optic tract can be determined from microstimulation-evoked visual sensations and recordings of flash-evoked potentials. In addition, microstimulation-evoked motor and sensory responses allow the internal capsule to be identified. The data collected using this technique are an important adjunct to selecting optimum sites to place electrocoagulation lesions for stereotactic posteroventral pallidotomy for refractory Parkinson's disease.
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