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M R DeLong

Publications and source records attributed to M R DeLong.

At least 19 recordsLinked to original sources
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

Functional and pathophysiological models of the basal ganglia.

Because of new data, anatomical and functional models of the basal ganglia in normal and pathological conditions (e.g. Parkinson's and Huntington's diseases) have recently come under greater scrutiny. An update of these models is clearly timely, taking into consideration not only changes in neuronal discharge rates, but also changes in the patterning and synchronization of neuronal discharge, the role of extrastriatal dopamine, and expanded intrinsic and input/output connections of these nuclei.

Animals↗
PubMed1996

Microstimulation of primate motor thalamus: somatotopic organization and differential distribution of evoked motor responses among subnuclei.

1. The functional organization of motor responses to microstimulation throughout the primate "motor" thalamus including nucleus ventralis lateralis, pars oralis (VLo); nucleus ventralis posterior lateralis, pars oralis (VPLo); nucleus ventralis lateralis, pars caudalis (VLc); and portions of ventralis anterior (VA) and area X, was systematically studied in awake monkeys. A total of 2,021 sites were examined for their response to microstimulation. Of these, 1,123 were histologically verified as to their location within the motor thalamus. At or near each site, isolated neurons were examined for their responses to somatosensory examination and active movement (n = 1,272). This study was carried out as part of a larger study examining the responses of neurons in the motor thalamus to somatosensory examination, torque-induced limb perturbations, and active movement in a visuomotor step-tracking task. 2. Microstimulation at < or = 40 microA evoked movements in the contralateral limbs, trunk, or face. Evoked movements of the limb were generally maximal about a single joint. 3. There was a differential response to microstimulation between subnuclei of the motor thalamus. In order of decreasing frequency, the percentages of sites within each subnucleus from which movements were evoked were as follows: VPLo, 93% (449 of 483); VLo, 21% (57 of 272); VLc, 11% (15 of 140); VA, 1% (1 of 85); and reticular nucleus, 0% (0 of 65). In VPLc, 44% (34 of 78) of sites examined were microexcitable. However, these were almost all within 500 microns of the border of VPLo, suggesting they may have occurred as a result of current spread to adjacent VPLo. Although area X was not sampled in its entirety, it did not appear to be microexcitable. 4. Microexcitable responses had a somatotopic organization, similar to that for neuronal responses to sensorimotor examination, with leg responses found most laterally and arm and face responses found progressively more medially. 5. Zones in VPLo generally ranging from 500 to 1,500 microns were found in which microstimulation resulted in the same motor response. These microexcitable zones resemble those described for the striatum and were termed thalamic microexcitable zones (TMZ). TMZs also resemble cortical efferent zones in that both are somatotopically organized, may affect a single muscle or group of muscles, have low thresholds for microstimulation with sharp boundaries that lie adjacent to other microexcitable zones with the opposite effects, and are of approximately the same dimension. 6. This study suggest that a fundamental unit of motor organization, i.e., single muscle or joint, is preserved at the thalamic level in the form of TMZs, and that these fundamental units of organization may contribute to the modular organization of the cortex.

Animals↗
PubMed1994

Synaptic innervation of neurones in the internal pallidal segment by the subthalamic nucleus and the external pallidum in monkeys.

In order to better understand the way by which the subthalamic nucleus interacts with the globus pallidus to control the output of the basal ganglia, we carried out a series of experiments to investigate the pattern of synaptic innervation of the pallidal neurones by the subthalamic terminals in the squirrel monkey. To address this problem we used the anterograde transport of biocytin. Following injections of biocytin in the subthalamic nucleus, rich plexuses of labelled fibres and varicosities formed bands that lay along the medullary lamina in both segments of the ipsilateral pallidum. At the electron microscopic level, two populations of biocytin-containing terminals were identified in the internal pallidum (GPi). A first group of small to medium-sized terminals (type 1; mean cross-sectional area +/- S.D. = 0.41 +/- 0.04 microns 2) contained round vesicles and formed asymmetric synapses with dendritic shafts (95%) of mixed sizes (maximum diameter ranging from 0.3 to 4.0 microns) and spine-like structures (5%). The second group of terminals (type 2) contained pleiomorphic vesicles, had a larger cross-sectional area (mean +/- S.D. = 0.9 +/- 0.4 micron 2) and formed symmetric synapses predominantly with perikarya (41%) and large dendrites (57%). In some cases, the two types of terminals converged at the level of single GPi neurones. Postembedding immunogold method revealed that the type 2 terminals displayed gamma-aminobutyric acid (GABA) immunoreactivity, whereas the type 1 terminals did not. In the external pallidum (GPe), injections in the subthalamic nucleus labelled both type 1 or type 2 terminals. However, the labelled type 2 boutons were much less abundant in GPe than in GPi. The presence of biocytin-labelled perikarya in GPe and the fact that the type 2 terminals displayed GABA immunoreactivity led us to suspect that these terminals were derived from axons of GPe neurones. In agreement with this hypothesis, injections of Phaseolus vulgaris-leucoagglutinin (PHA-L) in GPe labelled terminals in GPi that displayed the morphological features and a pattern of synaptic organization similar to the type 2 terminals. In conclusion, the results of our study demonstrate that the subthalamopallidal terminals form asymmetric synapses that are distributed along the dendritic tree of GPe and GPi neurones. In contrast, the GPe projection to GPi gives rise to large GABA-containing terminals that form symmetric synapses predominantly with the proximal region of pallidal neurones.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Physiologic properties and somatotopic organization of the primate motor thalamus.

1. To examine the functional organization of the primate "motor" thalamus, neuronal activity was studied systematically in awake behaving monkeys throughout the nucleus ventralis lateralis, pars oralis (VLo), nucleus ventralis posterior lateralis, pars oralis (VPLo), ventralis lateralis, pars caudalis (VLc), and portions of ventralis anterior (VA) and Area X. In addition, portions of the sensory nucleus ventralis posterior lateralis, pars caudalis (VPLc) were explored. Isolated neurons were examined for their responses to somatosensory examination and active movement (n = 919) and for their response to torque-induced joint displacements (n = 375). A total of 684 neurons was determined histologically to lie within specific subnuclei of the motor (n = 574) or sensory (n = 110) thalamus. 2. The sensorimotor response properties of neurons in the thalamic subnuclei showed clear differences in their response to somatosensory examination. In order of decreasing frequency, the percent of neurons responding to passive somatosensory examination in each subnucleus were as follows: VPLc, 96% (106/110), VPLo, 93% (252/270), VLc, 77% (43/56), VLo, 37% (59/155), Area X, 22% (12/53), and VA, 12% (5/40). Conversely, neurons that responded only to active movement were most frequent in VLo, 44% (68/155), VA, 45% (18/40), and Area X, 40% (21/53) and relatively infrequent in VLc 11% (6/56) and VPLo, 3% (7/270). In VPLc, no neurons were found that responded only to active movement (0/110). 3. A well-defined somatotopic organization was found in VLo, VPLo, and VPLc and was suggested strongly for VLc. Individual body regions were represented in a series of lamellae, organized in a partial onion skin-like arrangement with the leg represented in the outermost lamella, and the trunk, arm, and orofacial regions represented in successively deeper lamellae. In general the body representations, although present for each subnucleus thoroughly examined, i.e., VLo, VPLo, and VPLc, also were contiguous across subnuclei. Based on the available data, a clear somatotopic picture could not be discerned for Area X or VA. 4. Responses to torque application were more common in neurons in VPLo (77%; 60/78) and VLc (73%; 16/22) than in VLo (44%; 12/27). Mean latencies were shortest for neurons in VPLo (25 +/- 14 ms; mean +/- SD) and the bordering (shell) region of VPLc (22 +/- 15 ms) and were approximately twice as long in VLc (51 +/- 23 ms) and VLo (47 +/- 21 ms).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗