title: Single-unit analysis of the human posterior hypothalamus and red nucleus during deep brain stimulation for aggressivity.
abstract: OBJECTIVE Deep brain stimulation (DBS) of the posterior hypothalamus (PH) has been reported to be effective for aggressive behavior in a number of isolated cases. Few of these case studies have analyzed single-unit recordings in the human PH and none have quantitatively analyzed single units in the red nucleus (RN). The authors report on the properties of ongoing neuronal discharges in bilateral trajectories targeting the PH and the effectiveness of DBS of the PH as a treatment for aggressive behavior. METHODS DBS electrodes were surgically implanted in the PH of 1 awake patient with Sotos syndrome and 3 other anesthetized patients with treatment-resistant aggressivity. Intraoperative extracellular recordings were obtained from the ventral thalamus, PH, and RN and analyzed offline to discriminate single units and measure firing rates and firing patterns. Target location was based on the stereotactic coordinates used by Sano et al. in their 1970 study and the location of the dorsal border of the RN. RESULTS A total of 138 units were analyzed from the 4 patients. Most of the PH units had a slow, irregular discharge (mean [± SD] 4.5 ± 2.7 Hz, n = 68) but some units also had a higher discharge rate (16.7 ± 4.7 Hz, n = 15). Two populations of neurons were observed in the ventral thalamic region as well, one with a high firing rate (mean 16.5 ± 6.5 Hz, n = 5) and one with a low firing rate (mean 4.6 ± 2.8 Hz, n = 6). RN units had a regular firing rate with a mean of 20.4 ± 9.9 Hz and displayed periods of oscillatory activity in the beta range. PH units displayed a prolonged period of inhibition following microstimulation compared with RN units that were not inhibited. Patients under anesthesia showed a trend for lower firing rates in the PH but not in the RN. All 4 patients displayed a reduction in their aggressive behavior after surgery. CONCLUSIONS During PH DBS, microelectrode recordings can provide an additional mechanism to help identify the PH target and surrounding structures to be avoided such as the RN. PH units can be distinguished from ventral thalamic units based on their response to focal microstimulation. The RN has a characteristic higher firing rate and a pattern of beta oscillations in the spike trains. The effect of the anesthetic administered should be considered when using microelectrode recordings. The results of this study, along with previous reports, suggest that PH DBS may be an effective treatment for aggression.
authors.affiliation: Departments of 1 Physiology and.|Krembil Research Institute, Toronto, Ontario, Canada; and.
authors.forename: Robert
authors.initials: R
authors.lastname: Micieli
authors.affiliation: Centros Especializados de Hospital Universitario San Vicente Fundacion, Medellin-Rionegro, Colombia.
authors.forename: Adriana Lucia Lopez
authors.initials: AL
authors.lastname: Rios
authors.affiliation: Centros Especializados de Hospital Universitario San Vicente Fundacion, Medellin-Rionegro, Colombia.
authors.forename: Ricardo Plata
authors.initials: RP
authors.lastname: Aguilar
authors.affiliation: Centros Especializados de Hospital Universitario San Vicente Fundacion, Medellin-Rionegro, Colombia.
authors.forename: Luis Fernando Botero
authors.initials: LF
authors.lastname: Posada
authors.affiliation: Departments of 1 Physiology and.|Surgery, University of Toronto.|Krembil Research Institute, Toronto, Ontario, Canada; and.
authors.forename: William D
authors.initials: WD
authors.lastname: Hutchison
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000293:Adolescent; D000374:Aggression / Q000502:physiology*; D000758:Anesthesia; D002648:Child; D046690:Deep Brain Stimulation; D005260:Female; D006801:Humans; D007034:Hypothalamus, Posterior / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D012012:Red Nucleus / Q000187:drug effects / Q000503:physiopathology*; D058495:Sotos Syndrome / Q000503:physiopathology / Q000628:therapy; D013238:Stereotaxic Techniques; D016896:Treatment Outcome; D055815:Young Adult
keywords: DBS = deep brain stimulation; GABA = γ-aminobutyric acid; GPi = globus pallidus internus; MOAS = Modified Overt Aggression Scale; PH = posterior hypothalamus; QOLS = Quality of Life Scale; RN = red nucleus; SNr = substantia nigra; Sotos syndrome; aggression; deep brain stimulation; functional neurosurgery; intraoperative recordings; microelectrode recordings; microstimulation