✓ Optical and electron microscopic examinations were made of a biopsy sample of the ninth and 10th cranial nerves obtained during posterior fossa surgery for the relief of pain in a patient suffering from glossopharyngeal neuralgia (GN). Pathological findings, which were restricted to a small fraction of fascicles in the nerves, included large patches of demyelinated axons in close membrane-to-membrane apposition to one another and zones of less severe myelin damage (dysmyelination). These observations, in the light of similar morphological changes observed in biopsy samples excised from patients with trigeminal neuralgia, and new information on the pathophysiological characteristics of injured peripheral nerve axons, can account for much of the symptomatology of GN.
Marshall Devor, Ruth Govrin-Lippmann, Z. Harry Rappaport, Ronald R. Tasker, and Jonathan O. Dostrovsky
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.
Robert E. Gross, Edward G. Jones, Jonathan O. Dostrovsky, Catherine Bergeron, Anthony E. Lang, and Andres M. Lozano
✓ Chronic electrical stimulation of the thalamus is an effective treatment for essential and parkinsonian tremor. Although the preferred surgical target is generally accepted to lie within the ventral intermediate nucleus (Vim), the relationship between the surgically defined target and the true histologically defined target is addressed in only a few reports, due in large measure to the need for advanced cytoarchitectonic techniques to define the borders of the thalamic nuclei. The authors report on a patient who underwent effective thalamic deep brain stimulation (DBS) for tremor. By defining the boundaries of the thalamic nuclei, they were able to relate effective DBS to electrode location within the anterior region of the ventral posterior lateral nucleus—the proprioceptive shell of the sensory nucleus—and the posteroventral region of the ventral lateral nucleus, which are equivalent to the Vim defined by Hassler, et al.
Jason A. Brodkey, Ronald R. Tasker, Clement Hamani, Mary Pat McAndrews, Jonathan O. Dostrovsky, and Andres M. Lozano
Object. Thalamic neurons firing at frequencies synchronous with tremor are thought to play a critical role in the generation and maintenance of tremor. The authors studied the incidence and locations of neurons with tremor-related activity (TRA) in the thalamus of patients with varied pathological conditions—including Parkinson disease (PD), essential tremor (ET), multiple sclerosis (MS), and cerebellar disorders—to determine whether known differences in the effectiveness of thalamic stereotactic procedures for these tremors could be correlated to differences in the incidence or locations of TRA cells.
Methods. Seventy-five operations were performed in 61 patients during which 686 TRA cells were recorded from 440 microelectrode trajectories in the thalamus. The locations of the TRA cells in relation to electrophysiologically defined thalamic nuclei and the commissural coordinates were compared among patient groups.
The authors found that TRA cells are present in patients with each of these disorders and that these cells populate several nuclei in the ventral lateral tier of the thalamus. There were no large differences in the locations of TRA cells among the different diagnostic classes, although there was a difference in the incidence of TRA cells in patients with PD, who had greater than 3.8 times more cells per thalamic trajectory than patients with ET and approximately five times more cells than patients with MS or cerebellar disorders.
Conclusions. There was an increased incidence of TRA in the thalamus of patients with PD. The location of thalamic TRA cells in patients with basal ganglia and other tremor disorders was similar.
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.
Frederick A. Lenz, Jonathan O. Dostrovsky, Hon C. Kwan, Ronald R. Tasker, Katsumi Yamashiro, and John T. Murphy
✓ An apparatus and technique are described for microstimulation and recording of both slow wave and single neuron (single unit) activities during functional stereotaxic procedures. This method facilitates microstimulation and evoked potential and single unit analysis which, in combination, provide optimum definition of stereotaxic targets in the treatment of functional disorders of the human central nervous system.
Karen D. Davis, Ethan Taub, Frank Duffner, Andres M. Lozano, Ronald R. Tasker, Sylvain Houle, and Jonathan O. Dostrovsky
Object. Deep brain stimulation (DBS) of the sensory thalamus has been used to treat chronic, intractable pain. The goal of this study was to investigate the thalamocortical pathways activated during thalamic DBS.
Methods. The authors compared positron emission tomography (PET) images obtained before, during, and after DBS in five patients with chronic pain. Two of the five patients reported significant DBS-induced pain relief during PET scanning, and the remaining three patients did not report any analgesic effect of DBS during scanning. The most robust effect associated with DBS was activation of the anterior cingulate cortex (ACC). An anterior ACC activation was sustained throughout the 40 minutes of DBS, whereas a more posteriorly located ACC activation occurred at a delay after onset of DBS, although these activations were not dependent on the degree of pain relief reported during DBS. However, implications specific to the analgesic effect of DBS require further study of a larger, more homogeneous patient population. Additional effects of thalamic DBS were detected in motor-related regions (the globus pallidus, cortical area 4, and the cerebellum) and visual and association cortical areas.
Conclusions. The authors demonstrate that the ACC is activated during thalamic DBS in patients with chronic pain.
Karen D. Davis, Ethan Taub, Frank Duffner, Andres M. Lozano, Ronald R. Tasker, Sylvain Houle, and Jonathan O. Dostrovsky
Deep brain stimulation (DBS) of the sensory thalamus has been used to treat chronic, intractable pain. The goal of this study was to investigate the thalamocortical pathways activated during thalamic DBS.
The authors compared positron emission tomography (PET) images obtained before, during, and after DBS in five patients with chronic pain. Two of the five patients reported significant DBS-induced pain relief during PET scanning, and the remaining three patients did not report any analgesic effect of DBS during scanning. The most robust effect associated with DBS was activation of the anterior cingulate cortex (ACC). An anterior ACC activation was sustained throughout the 40 minutes of DBS, whereas a more posteriorly located ACC activation occurred at a delay after onset of DBS, although these activations were not dependent on the degree of pain relief reported during DBS. However, implications specific to the analgesic effect of DBS require further study of a larger, more homogeneous patient population. Additional effects of thalamic DBS were detected in motor-related regions (the globus pallidus, cortical area 4, and the cerebellum) and visual and association cortical areas.
The authors demonstrate that the ACC is activated during thalamic DBS in patients with chronic pain.
Diellor Basha, Jonathan O. Dostrovsky, Suneil K. Kalia, Mojgan Hodaie, Andres M. Lozano, and William D. Hutchison
The amputation of an extremity is commonly followed by phantom sensations that are perceived to originate from the missing limb. The mechanism underlying the generation of these sensations is still not clear although the development of abnormal oscillatory bursting in thalamic neurons may be involved. The theory of thalamocortical dysrhythmia implicates gamma oscillations in phantom pathophysiology although this rhythm has not been previously observed in the phantom limb thalamus. In this study, the authors report the novel observation of widespread 38-Hz gamma oscillatory activity in spike and local field potential recordings obtained from the ventral caudal somatosensory nucleus of the thalamus (Vc) of a phantom limb patient undergoing deep brain stimulation (DBS) surgery. Interestingly, microstimulation near tonically firing cells in the Vc resulted in high-frequency, gamma oscillatory discharges coincident with phantom sensations reported by the patient. Recordings from the somatosensory thalamus of comparator groups (essential tremor and pain) did not reveal the presence of gamma oscillatory activity.
Ali R. Rezai, Andres M. Lozano, Adrian P. Crawley, Michael L. G. Joy, Karen D. Davis, Chun L. Kwan, Jonathan O. Dostrovsky, Ronald R. Tasker, and David J. Mikulis
The utility of functional magnetic resonance (fMR) imaging in patients with implanted thalamic electrodes has not yet been determined. The aim of this study was to establish the safety of performing fMR imaging in patients with thalamic deep brain stimulators and to determine the value of fMR imaging in detecting cortical and subcortical activity during stimulation.
Functional MR imaging was performed in three patients suffering from chronic pain and two patients with essential tremor. Two of the three patients with pain had undergone electrode implantation in the thalamic sensory ventralis caudalis (Vc) nucleus and the other had undergone electrode implantation in both the Vc and the periventricular gray (PVG) matter. Patients with tremor underwent electrode implantation in the ventralis intermedius (Vim) nucleus. Functional MR imaging was performed during stimulation by using a pulse generator connected to a transcutaneous extension lead. Clinically, Vc stimulation evoked paresthesias in the contralateral body, PVG stimulation evoked a sensation of diffuse internal body warmth, and Vim stimulation caused tremor arrest.
Functional images were acquired using a 1.5-tesla MR imaging system. The Vc stimulation at intensities provoking paresthesias resulted in activation of the primary somatosensory cortex (SI). Stimulation at subthreshold intensities failed to activate the SI. Additional stimulation-coupled activation was observed in the thalamus, the secondary somatosensory cortex (SII), and the insula. In contrast, stimulation of the PVG electrode did not evoke paresthesias or activate the SI, but resulted in medial thalamic and cingulate cortex activation. Stimulation in the Vim resulted in thalamic, basal ganglia, and SI activation.
An evaluation of the safety of the procedure indicated that significant current could be induced within the electrode if a faulty connecting cable (defective insulation) came in contact with the patient. Simple precautions, such as inspection of wires for fraying and prevention of their contact with the patient, enabled the procedure to be conducted safely. Clinical safety was further corroborated by performing 86 MR studies in patients in whom electrodes had been implanted with no adverse clinical effects.
This is the first report of the use of fMR imaging during stimulation with implanted thalamic electrodes. The authors' findings demonstrate that fMR imaging can safely detect the activation of cortical and subcortical neuronal pathways during stimulation and that stimulation does not interfere with imaging. This approach offers great potential for understanding the mechanisms of action of deep brain stimulation and those underlying pain and tremor generation.