✓ Methods for localizing the posteroventral globus pallidus internus 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.
Andres Lozano, William Hutchison, Zelma Kiss, Ronald Tasker, Karen Davis, and Jonathan Dostrovsky
Luka R. Srejic, Taufik A. Valiante, Michelle M. Aarts, and William D. Hutchison
The postischemic brain has greater susceptibility to epileptogenic activity than physiologically healthy tissue. Epileptiform discharges are thought to exacerbate postischemic brain function. The aim of this study was to develop an in vivo focal stroke model in rats to characterize epileptiform activity.
The authors developed a parasagittal 8-channel intracortical microelectrode array to obtain recordings of cortical oscillations of local field potentials following partial middle and anterior cerebral artery occlusion. All experiments were done in urethane-anesthetized Sprague-Dawley rats.
Theta runs (TRs), ranging in duration from 5 seconds to 5 minutes, were observed in 62% of animals within 1 hour of occlusion. High-frequency oscillations (HFOs) in the high gamma range (80–120 Hz) were observed 5–15 seconds before each TR and terminated at the onset of the discharge. Periodic epileptiform discharges (PEDs) were detected in 54% of rats following ischemia. The PEDs consisted of an early negative slow wave, a high-amplitude positive spike, and a short negative slow wave. Transient HFOs in the low gamma range (30–70 Hz) occurred during the first negative wave and the rising phase of the positive spike of the PED.
These recordings provide the first intracortical evidence of a high-frequency component that could be an important element for diagnosis and intervention in postischemic epileptogenic activity. The early onset also suggests that HFOs could serve as a reliable method of detecting small epileptiform events and could be used as a consideration in deciding whether antiepileptic medications are appropriate as part of a patient's poststroke care.
Hiroki Toda, Clement Hamani, Adrian P. Fawcett, William D. Hutchison, and Andres M. Lozano
To examine the influence of deep brain stimulation on hippocampal neurogenesis in an adult rodent model.
Rats were anesthetized and treated for 1 hour with electrical stimulation of the anterior nucleus of the thalamus (AN) or sham surgery. The animals were injected with 5′-bromo-2′-deoxyuridine (BrdU) 1–7 days after surgery and killed 24 hours or 28 days later. The authors counted the BrdU-positive cells in the dentate gyrus (DG) of the hippocampus. To investigate the fate of these cells, they also stained sections for doublecortin, NeuN, and GFAP and analyzed the results with confocal microscopy. In a second set of experiments they assessed the number of DG BrdU-positive cells in animals treated with corticosterone (a known suppressor of hippocampal neurogenesis) and sham surgery, corticosterone and AN stimulation, or vehicle and sham surgery.
Animals receiving AN high-frequency stimulation (2.5 V, 90 μsec, 130 Hz) had a 2- to 3-fold increase in the number of DG BrdU-positive cells compared with nonstimulated controls. This increase was not seen with stimulation at 10 Hz. Most BrdU-positive cells assumed a neuronal cell fate. As expected, treatment with corticosterone significantly reduced the number of DG BrdU-positive cells. This steroid-induced reduction of neurogenesis was reversed by AN stimulation.
High-frequency stimulation of the AN increases the hippocampal neurogenesis and restores experimentally suppressed neurogenesis. Interventions that increase hippocampal neurogenesis have been associated with enhanced behavioral performance. In this context, it may be possible to use electrical stimulation to treat conditions associated with impairment of hippocampal function.
Aviva Abosch, William D. Hutchison, Jean A. Saint-Cyr, Jonathan O. Dostrovsky, and Andres M. Lozano
Object. The subthalamic nucleus (STN) is a target in the surgical treatment of Parkinson disease (PD). Little is known about the neurons within the human STN that modulate movement. The authors' goal was to examine the distribution of movement-related neurons within the STN of humans by using microelectrode recording to identify neuronal receptive fields.
Methods. Data were retrospectively collected from microelectrode recordings that had been obtained in 38 patients with PD during surgery for placement of STN deep brain stimulation electrodes. The recordings had been obtained in awake, nonsedated patients. Antiparkinsonian medications were withheld the night before surgery. Neuronal discharges were amplified, filtered, and displayed on an oscilloscope and fed to an audio monitor. The receptive fields were identified by the presence of reproducible, audible changes in the firing rate that were time-locked to the movement of specific joint(s).
The median number of electrode tracks per patient was six (range two–nine). The receptive fields were identified in 278 (55%) of 510 STN neurons studied. One hundred one tracks yielded receptive field data. Fourteen percent of 64 cells tested positive for face receptive fields, 32% of 687 cells tested positive for upper-extremity receptive fields, and 21% of 242 cells tested positive for lower-extremity receptive fields. Sixty-eight cells (24%) demonstrated multiple-joint receptive fields. Ninety-three cells (65%) with movement-related receptive fields were located in the dorsal half of the STN, and 96.8% of these were located in the rostral two thirds of the STN. Analysis of receptive field locations from pooled data and along individual electrode tracks failed to reveal a consistent somatotopic organization.
Conclusions. Data from this study demonstrate a regional compartmentalization of neurons with movement-related receptive fields within the STN, supporting the existence of specific motor territories within the STN in patients suffering from PD.
Myriam Lafreniere-Roula, William D. Hutchison, Andres M. Lozano, Mojgan Hodaie, and Jonathan O. Dostrovsky
The aim of the current study was to examine and compare the aftereffects of local high-frequency microstimulation through the recording electrode on the firing of neurons in the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr) in patients undergoing surgery for deep brain stimulation. Deep brain stimulation has been playing an increasing role in the treatment of Parkinson disease, with the subthalamic nucleus (STN) being the preferred implantation target. Changes in cellular activity indicative of the borders of the STN are typically used during surgery to determine the extent of the STN and locate the optimal target, but in some cases borders may be difficult to identify. In this study the authors compared the effects of microstimulation in the SNr and STN. In previous studies they have shown that microstimulation in the internal globus pallidus, which is functionally similar to the SNr, inhibits firing, whereas similar microstimulation in the STN has minimal effect. The presence of inhibition in the SNr but not in the STN could be used as an additional criterion to help identify the location of the border between the STN and SNr.
Dual microelectrode recordings were performed during stereotactic surgery in 4 patients. Well-isolated high-amplitude units were stimulated extracellularly through the recording microelectrode with 0.5-second trains of high frequency (200 Hz) and low current (≤ 5 μA).
In the majority (92%) of SNr neurons, this type of stimulation led to a period of inhibition lasting several hundreds of milliseconds following the end of the train. In contrast, only 1 neuron of 70 judged to be in the STN by other criteria was inhibited by this type of microstimulation, and this neuron was located at the ventral border of the STN.
These findings indicate that prolonged inhibition of firing following low-amplitude high-frequency microstimulation via the recording electrode is a consistent feature of almost all SNr neurons and rarely if ever occurs in STN neurons. This feature therefore provides a useful additional finding that can be used to help identify the border between the STN and SNr.
Robert Micieli, Adriana Lucia Lopez Rios, Ricardo Plata Aguilar, Luis Fernando Botero Posada, and William D. Hutchison
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.
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.
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.
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.
Jean A. Saint-Cyr, Tasnuva Hoque, Luiz C. M. Pereira, Jonathan O. Dostrovsky, William D. Hutchison, David J. Mikulis, Aviva Abosch, Elspeth Sime, Anthony E. Lang, and Andres M. Lozano
Object. The authors sought to determine the location of deep brain stimulation (DBS) electrodes that were most effective in treating Parkinson disease (PD).
Methods. Fifty-four DBS electrodes were localized in and adjacent to the subthalamic nucleus (STN) postoperatively by using magnetic resonance (MR) imaging in a series of 29 patients in whom electrodes were implanted for the treatment of medically refractory PD, and for whom quantitative clinical assessments were available both pre- and postoperatively. A novel MR imaging sequence was developed that optimized visualization of the STN. The coordinates of the tips of these electrodes were calculated three dimensionally and the results were normalized and corrected for individual differences by using intraoperative neurophysiological data (mean 5.13 mm caudal to the midcommissural point [MCP], 8.46 mm inferior to the anterior commissure—posterior commissure [AC—PC], and 10.2 mm lateral to the midline).
Despite reported concerns about distortion on the MR image, reconstructions provided consistent data for the localization of electrodes. The neurosurgical procedures used, which were guided by combined neuroimaging and neurophysiological methods, resulted in the consistent placement of DBS electrodes in the subthalamus and mesencephalon such that the electrode contacts passed through the STN and dorsally adjacent fields of Forel (FF) and zona incerta (ZI). The mean location of the clinically effective contacts was in the anterodorsal STN (mean 1.62 mm posterior to the MCP, 2.47 mm inferior to the AC—PC, and 11.72 mm lateral to the midline). Clinically effective stimulation was most commonly directed at the anterodorsal STN, with the current spreading into the dorsally adjacent FF and ZI.
Conclusions. The anatomical localization of clinically effective electrode contacts provided in this study yields useful information for the postoperative programming of DBS electrodes.
Cristina V. Torres, Elena Moro, Jonathan O. Dostrovsky, William D. Hutchison, Yu-Yan W. Poon, and Mojgan Hodaie
Bilateral deep brain stimulation of the globus pallidus pars interna (GPi) is the favored neuromodulation procedure in cases of cervical dystonia. The authors report on a case of unilateral GPi implantation that resulted in sustained benefit with marked improvement in pain and dystonia.