Electroencephalography and Clinical Neurophysiology, 1980, 49:585--599 585 © Elsevier/North-Holland Scientific Publishers, Ltd. EFFECTS OF CEREBELLAR STIMULATION ON UNITARY ACTIVITY WITHIN A CHRONIC EPILEPTIC FOCUS IN A PRIMATE T.J. EBNER, H. BANTLI 1 and J.R. BLOEDEL Department of Neurosurgery, University of Minnesota, B590 Mayo Memorial Building, 420 Delaware Street S.E., Minneapolis, Minn. 55455 (U.S.A.) (Accepted for publication: March 4, 1980) Several experimental studies have reported that stimulation of the cerebellum can arrest or reduce seizure discharge in experimentally induced neocortical focal epilepsy (Cooke and Snider 1955; Dow et al. 1962; Hutton et al. 1972). Furthermore, in models of secondary generalized epilepsy, cerebellar stimulation has been shown to reduce paroxysmal events (Hablitz 1976) and elevate seizure thresholds (Strain et al. 1978). Also hippocampal seizure activity in experimental animals can be sup- pressed by cerebellar stimulation (Iwata and Snider 1959; Mutani et al. 1969; Babb et al. 1974; Maiti and Snider 1975). Based on these experimental studies, cerebellar stimulation has been therapeutically employed for con- trol of intractable seizures in man (Cooper et al. 1973, 1974). However, the data from several other animal and human studies are conflicting. Cerebellar stimulation did not effectively sup- press seizure activity in a number of phar- macological models of generalized seizures in cats (Myers et al. 1975) nor in electrically evoked seizures in primates (Hemmy et al. 1977). Similarly, stimulation of the dentate or fastigial nuclei did not significantly alter seizure activity in squirrel monkeys with cobalt-induced neocortical seizures (Grimm et al. 1970). In cats, cobalt-induced seizures were accentuated by cerebellar stimulation 1 Central Research Laboratories -- 3M, Biosciences Research Laboratory, Building 218-2, P.O. Box 33221, St. Paul, Minn. 55133, U.S.A. (Reimer et al. 1967), and high-frequency cere- bellar stimulation activated seizures in primates with alumina cream foci (Hablitz et al. 1975). In a preliminary report of a double blind study examining the effects of cerebel- lar stimulation in patients with epilepsy, a statistically significant reduction in seizure activity could not be documented (Van Buren et al. 1978). The precise explanation underlying the spectrum of effects produced by cerebellar stimulation may reside in the diversity of the paradigms employed. Several different species of animals as well as numerous seizure models have been used (see Myers et al. 1975). Per- haps of more importance than the different species and epilepsy models employed is the spectrum of stimulus parameters utilized for evaluating cerebellar stimulation. In most early studies no attempt was made to docu- ment electrode characteristics or charge den- sities used for stimulating the cerebellar sur- face (Cooke and Snider 1955; Iwata and Snider 1959; Dow et al. 1962; Reimer et al. 1967; Babb et al. 1974; Hablitz et al. 1975). The importance of stimulus parameters is emphasized by experiments showing that the effects of cerebellar stimulation including changes in seizure threshold are very depen- dent on stimulus parameters (Bantli et al. 1978; Strain et al. 1978). Additional variabil- ity may relate to the fact that the stimulation has been applied to many different regions of the cerebellum including multiple locations on the cerebellar surface (Dow et al. 1962;