Oscillations in the basal ganglia.
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Basal Ganglia↗
Biomedical subjects
M R DeLong
Publications and source records attributed to M R DeLong.
Stereotactic pallidotomy in the treatment of Parkinson disease: an expert opinion.
The objective of this workshop was to provide recommendations on several issues involving pallidotomy for patients with medically intractable Parkinson disease to physicians, patients, and other health care providers. An international consortium of experts in neurology, neurosurgery, and neurophysiology who had extensive experience with pallidotomy were invited to the workshop. Participants were sent background materials from the scientific literature for review-based participant recommendations. A proposed agenda was circulated to all participants before the workshop, and the final agenda was based on their recommendations. Topics were introduced at the workshop by members of the organizing committee, followed by extensive group discussion. A draft of a consensus statement, based on the previous day's discussion, was circulated and further modifications were made. The final statement was agreed on by all members. The conclusions of the participants were: (1) Pallidotomy should be performed only at centers that have a team of physicians with substantial expertise and experience in the field. (2) Patients with disabling idiopathic Parkinson disease, without dementia, and who have exhausted medical therapy should be considered for pallidotomy. (3) All patients should be examined by means of standardized rating scales both preoperatively and postoperatively to ensure quality of care at each center. (4) Symptoms that respond best to pallidotomy include medication-induced dyskinesias, rigidity, and tremor, while balance, gait disorders, and hypophonia are generally less responsive to surgery. Benefits of pallidotomy appear to be long lasting. (5) Each institution's complication rate should be discussed before surgery.
Counseling↗
Neuronal activity in the basal ganglia in patients with generalized dystonia and hemiballismus.
Microelectrode recording was performed in the basal ganglia of 3 patients with generalized dystonia and 1 patient with hemiballismus secondary to a brainstem hemorrhage. Neuronal activity was recorded from the internal and external segments of the globus pallidus and assessed for mean discharge rate and pattern of spontaneous activity. The responses of neurons in the internal segment of the globus pallidus to passive and active movements were also evaluated. Mean discharge rates of neurons in both segments of the pallidum in patients with dystonia and the patient with hemiballismus were considerably lower than those reported for patients with idiopathic Parkinson's disease. In addition, the pattern of spontaneous neuronal activity was highly irregular, occurring in intermittent grouped discharges separated by periods of pauses. Although receptive fields in the dystonia patients were widened and less specific than those reported in normal monkeys, neuronal responses to movement were uncommon in the hemiballismus patient. Before surgery, patients with dystonia experienced abnormal posturing and involuntary movements. Coactivation of agonist-antagonist muscle groups was observed both at rest and during the performance of simple movements. After pallidotomy there was a significant reduction in the involuntary movement associated with these disorders and a more normal pattern of electromyographic activity during rest and movement. Given the improvement in dystonic and hemiballistic movements in these patients after ablation of the sensorimotor portion of the internal segment of the globus pallidus, we suggest that pallidotomy can be an effective treatment for patients with dystonia and also for patients with medically intractable hemiballismus. Based on the finding of decreased neuronal discharge rates in pallidal neurons, we propose that physiologically dystonia most closely resembles a hyperkinetic movement disorder. A model for dystonia is proposed that incorporates the observed changes in the rate and pattern of neuronal activity in the pallidum with data from neuroimaging with positron emission tomography and 2-deoxyglucose studies.
Adult↗
Comparison of MPTP-induced changes in spontaneous neuronal discharge in the internal pallidal segment and in the substantia nigra pars reticulata in primates.
The basal ganglia are currently viewed as components of segregated corticosubcortical reentrant circuits. One of these circuits, the "motor" circuit, is critically involved in the development of parkinsonian motor signs. Current pathophysiologic models postulate that parkinsonism is associated with increased activity in the basal ganglia output nuclei. The neuronal activity in the motor portion of one of these output nuclei, the internal segment of the globus pallidus (GPi), has been characterized in detail in intact and parkinsonian animals, but the neuronal activity in the second major basal ganglia output nucleus, the substantia nigra pars reticulata (SNr), has received far less attention. This study in primates represents a comparison of the effects of parkinsonism, induced by injections of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), on the neuronal discharge in the GPi and SNr. These electrophysiologic recording experiments were carried out in three African green and two rhesus monkeys. One hundred and twenty-four neurons were recorded in the GPi before treatment with MPTP, and 93 neurons thereafter. In the SNr, 55 cells were recorded before treatment with MPTP, and 41 cells thereafter. MPTP induced a non-significant increase in the average discharge rate and a significant decrease in the median interspike interval length (ISI) in the GPi (by 13%), whereas no changes were detected in either parameter in the SNr. The average ISI distributions were markedly asymmetric in both structures, and could be modeled by a logarithmic normal distribution. With the MPTP treatment, the mode of the ISI distribution fell by 24% in the GPi (P< or =0.01), whereas it did not change significantly in the SNr. An algorithm that detects burst discharges in the raw ISI data (based on the method by Legendy and Salcman) detected a significant increase in the proportion of action potentials that participated in bursts of discharge in both structures (increase by 257% in the GPi, and by 67% in the SNr). Power spectral and autocorrelation analysis revealed that treatment with MPTP increased the proportion of cells with oscillatory burst patterns at 3-8 Hz in both structures (from 0.8% to 27% of all neurons in the GPi, and from none to 10% in the SNr). The results show that neuronal discharge in the SNr is affected in parkinsonism, but that the changes in the SNr are less pronounced then those seen in the GPi.
Animals↗
Thalamic single neuron activity in patients with dystonia: dystonia-related activity and somatic sensory reorganization.
Indirect evidence suggests that the thalamus contributes to abnormal movements occurring in patients with dystonia (dystonia patients). The present study tested the hypothesis that thalamic activity contributes to the dystonic movements that occur in such patients. During these movements, spectral analysis of electromyographic (EMG) signals in flexor and extensor muscles of the wrist and elbow exhibited peak EMG power in the lowest frequency band [0-0.78 Hz (mean: 0.39 Hz) dystonia frequency] for 60-85% of epochs studied during a pointing task. Normal controls showed low-frequency peaks for <16% of epochs during pointing. Among dystonia patients, simultaneous contraction of antagonistic muscles (cocontraction) at dystonia frequency during pointing was observed for muscles acting about the wrist (63% of epochs) and elbow (39%), but cocontraction was not observed among normal controls during pointing. Thalamic neuronal signals were recorded during thalamotomy for treatment of dystonia and were compared with those of control patients without motor abnormality who were undergoing thalamic procedures for treatment of chronic pain. Presumed nuclear boundaries of a human thalamic cerebellar relay nucleus (ventral intermediate, Vim) and a pallidal relay nucleus (ventral oral posterior, Vop) were estimated by aligning the anterior border of the principal sensory nucleus (ventral caudal, Vc) with the region where the majority of cells have cutaneous receptive fields (RFs). The ratio of power at dystonia frequency to average spectral power was >2 (P < 0.001) for cells in presumed Vop often for dystonia patients (81%) but never for control patients. The percentage of such cells in presumed Vim of dystonia patients (32%) was not significantly different from that of controls (31%). Many cells in presumed Vop exhibited dystonia frequency activity that was correlated with and phase-advanced on EMG activity during dystonia, suggesting that this activity was related to dystonia. Thalamic somatic sensory activity also differed between dystonia patients and controls. The percentage of cells responding to passive joint movement or to manipulation of subcutaneous structures (deep sensory cells) in presumed Vim was significantly greater in patients with dystonia than in control patients undergoing surgery for treatment of pain or tremor. Dystonia patients had a significantly higher proportion of deep sensory cells responding to movement of more than one joint (26%, 13/52) than did "control" patients (8%, 4/49). Deep sensory cells in patients with dystonia were located in thalamic maps that demonstrated increased representations of parts of the body affected by dystonia. Thus dystonia patients showed increased receptive fields and an increased thalamic representation of dystonic body parts. The motor activity of an individual sensory cell was related to the sensory activity of that cell by identification of the muscle apparently involved in the cell's receptive field. Specifically, we defined the effector muscle as the muscle that, by contraction, produced the joint movement associated with a thalamic neuronal sensory discharge, when the examiner passively moved the joint. Spike X EMG correlation functions during dystonia indicated that thalamic cellular activity less often was related to EMG in effector muscles (52%) than in other muscles (86%). Thus there is a mismatch between the effector muscle for a thalamic cell and the muscles with EMG correlated with activity of that cell during dystonia. This mismatch may result from the reorganization of sensory maps and may contribute to the simultaneous activation of multiple muscles observed in dystonia. Microstimulation in presumed Vim in dystonia patients produced simultaneous contraction of multiple forearm muscles, similar to the simultaneous muscle contractions observed in dystonia. (ABSTRACT TRUNCATED)
Brain Mapping↗
Amelioration of sensory limb discomfort of restless legs syndrome by pallidotomy.
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Anticonvulsants↗
The subthalamic nucleus and tremor in Parkinson's disease.
The role of the subthalamic nucleus (STN) in the origin of parkinsonian tremor is discussed. Previous studies in monkeys made parkinsonian by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) administration suggested a direct participation of the STN in the pathophysiology of tremor. We recorded tremor-related activity in the STN in 12 patients with Parkinson's disease (PD) and found that microstimulation of the sensorimotor region of the nucleus, where these neurons are present, stopped the tremor with a very short latency. Long-term treatment by means of bilateral deep-brain stimulation (DBS) in the same 12 patients led to a significant reduction of tremor as well as other cardinal features of PD. This effect was blindly assessed at 3 months after implantation. In another group of seven patients, a unilateral lesion of the STN was performed. Both postural and resting tremor were significantly improved on the limbs contralateral to the lesion side. In three patients, tremor disappeared completely after 12 months of follow up. The electrophysiologic data and therapeutic effect of inactivating the STN strongly indicated that this structure is directly involved in the origin of parkinsonian tremor, as suggested by the MPTP model.
Adult↗
Visual fields in patients with posterior GPi pallidotomy.
The objective of this study was to describe the incidence and types of visual field defects after posterior globus pallidus internus (GPi) pallidotomy for Parkinson's disease. The creation of the pallidotomy lesion carries a risk of damaging neighboring structures such as the optic tract. The reported frequency of visual field defects in patients after pallidotomy varies from 0 to 40%. Goldmann visual field testing was performed on 40 patients who underwent microelectrode-guided posterior GPi pallidotomy. The optic tract was identified during the procedure by listening during microelectrode recording for the evoked responses to light flashes and by assessing stimulation-induced subjective responses. After the first 18 patients, lesioning thresholds were increased from 0.5 to > or =1.0 mA so that the lesion was placed more distant from the optic tract. The location of individual lesions was determined on postsurgical MRI. Three patients (7.5%) had visual field defects likely related to the pallidotomy. These were contralateral homonymous superior quadrantanopias, associated in two patients with small paracentral scotomas. The incidence of visual field defects with the early technique was 11% (2/18) and decreased to 4.5% (1/22) after thresholds for lesioning were increased. Except for the location of the lesion relative to the optic tract (more ventral, adjacent to or extending into the optic tract), no other variable correlated with a post-pallidotomy visual field defect. Microelectrode-guided GPi pallidotomy is a relatively safe procedure as regards visual function even when the optic tract is used as a guide for lesion placement.
Adult↗
Microelectrode-guided pallidotomy: technical approach and its application in medically intractable Parkinson's disease.
OBJECT: The authors describe the microelectrode recording and stimulation techniques used for localizing the caudal sensorimotor portion of the globus pallidus internus (GPi) and nearby structures (internal capsule and optic tract) in patients undergoing GPi pallidotomy. METHODS: Localization is achieved by developing a topographic map of the abovementioned structures based on the physiological characteristics of neurons in the basal ganglia and the microexcitable properties of the internal capsule and optic tract. The location of the caudal GPi can be determined by "form fitting" the physiological map on relevant planes of a stereotactic atlas. A sensorimotor map can be developed by assessing neuronal responses to passive manipulation or active movement of the limbs and orofacial structures. The internal capsule and optic tract, respectively, can be identified by the presence of stimulation-evoked movement or the patient's report of flashes or speckles of light that occur coincident with stimulation. The optic tract may also be located by identifying the neural response to flashes of light. The anatomical/physiological map is used to guide lesion placement within the sensorimotor portion of the pallidum while sparing nearby structures, for example, the external globus pallidus, nucleus basalis, optic tract, and internal capsule. The lesion location and size predicted by using physiological recording together with thin-slice high-resolution magnetic resonance imaging reconstructions of the lesion were confirmed in one patient on histological studies. CONCLUSIONS: These data provide important information concerning target identification for ablative or deep brain stimulation procedures in idiopathic Parkinson's disease and other movement disorders.
Antiparkinson Agents↗
Models of basal ganglia function and pathophysiology of movement disorders.
Movement disorders are categorized as hypokinetic (Parkinson's disease) or hyperkinetic (Huntington's disease, hemiballism, or dystonia). Neuroscience research over the last several years, using data obtained in animal models for these disorders and data from patients undergoing stereotactic surgery, has greatly advanced the knowledge of the pathophysiologic basis of these diseases. This article offers a summary and critique of current models of the pathophysiology underlying hypokinetic and hyperkinetic diseases and a discussion of the implications of these models for neurosurgical procedures as treatment for these disorders.
Basal Ganglia↗
GPi pallidotomy for dystonia: clinical outcome and neuronal activity.
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Brain Mapping↗
Dopaminergic neurons intrinsic to the primate striatum.
Intrinsic, striatal tyrosine hydroxylase-immunoreactive (TH-i) cells have received little consideration. In this study we have characterized these neurons and their regulatory response to nigrostriatal dopaminergic deafferentation. TH-i cells were observed in the striatum of both control and 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP)-treated monkeys; TH-i cell counts, however, were 3.5-fold higher in the striatum of MPTP-lesioned monkeys. To establish the dopaminergic nature of the TH-i cells, sections were double-labeled with antibodies to dopamine transporter (DAT). Immunofluorescence studies demonstrated that nearly all TH-i cells were double-labeled with DAT, suggesting that they contain the machinery to be functional dopaminergic neurons. Two types of TH-i cells were identified in the striatum: small, aspiny, bipolar cells with varicose dendrites and larger spiny, multipolar cells. The aspiny cells, which were more prevalent, corresponded morphologically to the GABAergic interneurons of the striatum. Double-label immunofluorescence studies using antibodies to TH and glutamate decarboxylase (GAD67), the synthetic enzyme for GABA, showed that 99% of the TH-i cells were GAD67-positive. Very few (<1%) of the TH-i cells, however, were immunoreactive for the calcium-binding proteins calbindin and parvalbumin. In summary, these results demonstrate that the dopaminergic cell population of the striatum responds to dopamine denervation by increasing in number, apparently to compensate for loss of extrinsic dopaminergic innervation. Moreover, this population of cells corresponds largely with the intrinsic GABAergic cells of the striatum. This study also suggests that the adult primate striatum does retain some intrinsic capacity to compensate for dopaminergic cell loss.
Animals↗
Pallidotomy in Parkinson's disease increases supplementary motor area and prefrontal activation during performance of volitional movements an H2(15)O PET study.
Supplementary motor area and right dorsal prefrontal cortex activation in Parkinson's disease is selectively impaired during volitional limb movements. Since posteroventral pallidotomy improves motor performance in Parkinson's disease patients 'off' medication (i.e. off medication for 9-12 h), we hypothesized that it would also concomitantly increase supplementary motor area and dorsal prefrontal cortex activation. Six Parkinson's disease patients with a median total motor Unified Parkinson's Disease Rating Scale (UPDRS) of 52.5 (range 34-66) 'off' medication underwent unilateral right posteroventral pallidotomy. The patients had H2(15)O PET when 'off' medication before and 3-4 months after surgery. Each PET study comprised four to six measurements of regional cerebral blood flow either at rest or while performing regularly paced joystick movements in freely selected directions (forward, backward, left or right) using the left hand. Pre- and postoperative scans were performed in an identical manner and the associated levels of activation were compared using statistical parametric mapping. After pallidotomy, the median total motor UPDRS score 'off' medication decreased by 34.7% (P = 0.03) and mean response times of joystick movements following the pacing tones improved by 13.8% (P = 0.08). Relative increases in activation of the supplementary motor area and right dorsal prefrontal cortex were observed during joystick movements (P < 0.001). Decreased activation was seen in the region of the right pallidum (P = 0.001). We conclude that pallidotomy reduces pallidal inhibition of thalamocortical circuits and reverses, at least partially, the impairment of supplementary motor area and dorsal prefrontal cortex activation associated with Parkinson's disease.
Adult↗
Tactile spatial acuity and roughness discrimination: impairments due to aging and Parkinson's disease.
We used gratings of alternating ridges and grooves in a quantitative psychophysical investigation of tactile perception in patients with Parkinson's disease (PD) and age-matched normal controls. The groove width required for threshold discrimination of grating orientation was 25% higher in the control subjects compared to younger individuals studied previously (p = 0.004), indicating a small but significant decline in tactile spatial acuity with age. Relative to age-matched controls, patients with PD showed a twofold increase in the tactile spatial threshold (p = 3.07 x 10(-8), with somewhat greater impairment on the side more affected clinically (p = 0.03). Testing with the forearm prone, as compared to supine, produced a small improvement in the acuity of patients (p = 0.01) but not controls (p = 0.26). PD patients were also impaired in tactually discriminating grating roughness: their difference limens were over three times higher than those of controls (p = 5.74 x 10(-5)) for gratings differing in groove width, and over twice as high (p = 0.0003) for gratings differing in ridge width. We conclude that PD significantly impairs performance on these tactile tasks.
Adult↗
Posterior ventral pallidotomy: techniques and theoretical considerations.
1. Microeletrode mapping of the pallidum and adjacent structures allows for precise target identification and localization of critical structures, i.e., optic tract, internal capsule, and external pallidum, which must be spared from lesioning. 2. Microelectrode mapping has provided physiologic-anatomic correlation of determining the optimal target location as related to clinical outcome and has helped to refine the role of stimulation as a tool for target localization. 3. The improved accuracy of this technique should result in more accurate lesion placement which should improve long-term outcome and decrease morbidity.
Brain Mapping↗
Basal ganglia pathophysiology. A critical review.
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Animals↗
Microelectrode-guided pallidotomy for medically intractable Parkinson's disease.
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Brain Mapping↗
Treatment of advanced Parkinson's disease by posterior GPi pallidotomy: 1-year results of a pilot study.
The effects of posterior internal pallidal ablation (GPi pallidotomy) on parkinsonian signs and symptoms were studied in 15 patients with medically intractable Parkinson's disease (PD). The sensorimotor territory of the internal portion of the globus pallidus and the adjacent optic tract and internal capsule were identified with microelectrode recording and stimulation. Radiofrequency lesions were then created in the identified sensorimotor territory. Pallidotomy significantly improved all cardinal parkinsonian motor signs (tremor, rigidity, akinesia/bradykinesia, and gait dysfunction) and reduced drug-induced motor fluctuations and dyskinesias. The improvements occurred predominately contralateral to the lesion, but were also present ipsilaterally. Early postoperative (3-month), mean total United Parkinson's Disease Rating Scale scores improved by 30.1% from preoperative values. Mean combined "on/off" Schwab and England Scale scores, a measure of functional independence, increased from 48.8% to 73.0% postoperatively. The mean total United Parkinson's Disease Rating Scale and Schwab and England scores did not show a statistically significant decline over the 1-year postoperative period. Surgery resulted in little morbidity, including a lack of significant deficits on neuropsychological and psychiatric testing. Physical and social functioning and vitality measures on the Medical Outcome Scale also showed significant improvement over the postoperative period. The findings of this pilot study demonstrate that ablation of the sensorimotor portion of the internal pallidum is a highly effective treatment for advanced PD, with benefits sustained at 1 year.
Adult↗