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MRI evaluation of the basal ganglia size and iron content in patients with Parkinson's disease.

OBJECTIVE: To evaluate by MRI the area size and the degree of iron accumulation in basal ganglia nuclei that are implicated in the pathogenesis of Parkinson's disease (PD). METHODS: 40 patients with idiopathic PD and 40 controls were examined on a 1. 5 Tesla MR imager, using a multiecho SE sequence 2000/20, 40, 60, 80, 100, 120, 140, 160 (TR/TE). The T2 relaxation time (T2) and the area of substantia nigra zona compacta (SNc), substantia nigra zona reticulata (SNr), putamen (Pu), globus pallidus external (GPe), globus pallidus internal (GPi), caudate nucleus (CN), locus coeruleus (LC) and subthalamic nucleus (STN) were assessed. RESULTS: The T2 of SNc (76. 8 +/- 6. 0) was lower and of Pu (79.5 +/- 6.0) and GPe (69.5 +/- 7.0) was higher in patients than in controls (78.6 +/- 3.8, 77.4 +/- 3.9 and 67.3 +/- 5.7, respectively), p < 0.05. The area of CN (125.9 +/- 20.2) and Pu (201.5 +/- 48.7) was higher in patients than in controls (110.7 +/- 21.5 and 180.1 +/- 41.1, respectively), p < 0.05. A more pronounced decrease in the T2 of SNc (73.6 +/- 8.9) was observed when the more affected side of patients was evaluated separately. In patients with disease duration > 5 years the T2 of STN (71.5 +/- 6.3) was lower and the area of Pu was higher (215.3 +/- 54.9) compared with those with disease duration < or = 5 years (75.8 +/- 10.9 and 190.9 +/- 41.0 respectively), p < 0.05. CONCLUSIONS: These findings suggest that dysfunction of the basal ganglia circuitry in PD may affect iron content not only in SNc but in STN, Pu and GPe as well. Compensatory sprouting of the remaining dopaminergic fibers could account for the increased area of the CN and Pu.

Adult↗

Differentiation of sCJD and vCJD forms by automated analysis of basal ganglia intensity distribution in multisequence MRI of the brain--definition and evaluation of new MRI-based ratios.

We present a method for the analysis of basal ganglia (including the thalamus) for accurate detection of human spongiform encephalopathy in multisequence magnetic resonance imaging (MRI) of the brain. One common feature of most forms of prion protein diseases is the appearance of hyperintensities in the deep grey matter area of the brain in T2-weighted magnetic resonance (MR) images. We employ T1, T2, and Flair-T2 MR sequences for the detection of intensity deviations in the internal nuclei. First, the MR data are registered to a probabilistic atlas and normalized in intensity. Then smoothing is applied with edge enhancement. The segmentation of hyperintensities is performed using a model of the human visual system. For more accurate results, a priori anatomical data from a segmented atlas are employed to refine the registration and remove false positives. The results are robust over the patient data and in accordance with the clinical ground truth. Our method further allows the quantification of intensity distributions in basal ganglia. The caudate nuclei are highlighted as main areas of diagnosis of sporadic Creutzfeldt-Jakob Disease (sCJD), in agreement with the histological data. The algorithm permitted the classification of the intensities of abnormal signals in sCJD patient FLAIR images with a higher hypersignal in caudate nuclei (10/10) and putamen (6/10) than in thalami. Defining normalized MRI measures of the intensity relations between the internal grey nuclei of patients, we robustly differentiate sCJD and variant CJD (vCJD) patients, in an attempt to create an automatic classification tool of human spongiform encephalopathies.

Algorithms↗

[Learned equivalence in schizophrenia: novel method for the measurement of memory functions of the hippocampus and basal ganglia].

The purpose of the present study was to investigate basal ganglia (BG) and medial temporal lobe (MTL) dependent learning in patients with schizophrenia. Acquired equivalence is a phenomenon in which prior training to treat two stimuli as equivalent (if two stimuli are associated with the same response) increases generalization between them. The learning of stimulus-response pairs is related to the BG, whereas the MTL system participates in stimulus generalization. Forty-three patients with DSM-IV schizophrenia and 28 matched healthy controls participated in the study. Volunteers received the acquired equivalence associative learning task (FISHES) during which associations between faces and pet fishes are learned. Results revealed that patients with schizophrenia showed a selective deficit on stimulus generalization, whereas stimulus-response learning was unaffected. The number of errors during stimulus-response learning correlated with the daily chlorpromazine-equivalent dose of antipsychotics. In conclusion, patients with schizophrenia showed deficits during MTL-dependent learning, but not during BG-dependent learning. High-dose first generation antipsychotics may disrupt BG-dependent learning by blocking dopaminergic neurotransmission in the nigro-striatal system.

Adult↗

High-intensity basal ganglia lesions on T1-weighted MR images in neurofibromatosis.

Basal ganglia lesions, characterized on MR by increased signal intensity on T1-weighted images, were observed in seven patients with documented neurofibromatosis. These lesions most often involved the globus pallidus and internal capsules in a bilateral and symmetric fashion, and extended across the anterior commissure resulting in a "dumbbell" configuration. Smaller and less prominent foci of increased signal also were present on corresponding T2-weighted images. These lesions did not exhibit mass effect, edema, or enhancement with gadolinium-DTPA. They were not visible on CT (performed in two patients) and demonstrated no progression during a 2-year interval in three patients. Their signal characteristics and morphology suggest that they represent heterotopias containing Schwann cells and/or melanin deposits. Migrational abnormalities of these neural crest derivatives are known to occur in neurofibromatosis, and the presence of such heterotopias has been documented pathologically in patients with this disorder. While recent reports discuss foci of increased signal intensity on T2-weighted MR images in patients with neurofibromatosis, signal abnormalities on T1-weighted images have not yet been described. When lesions characterized by similar signal as well as morphologic characteristics are encountered on MR, the diagnosis of neurofibromatosis should be considered.

Adolescent↗

High-intensity basal ganglia lesions on T1-weighted MR images in neurofibromatosis.

Basal ganglia lesions, characterized on MR by increased signal intensity on T1-weighted images, were observed in seven patients with documented neurofibromatosis. These lesions most often involved the globus pallidus and internal capsules in a bilateral and symmetric fashion, and extended across the anterior commissure resulting in a "dumbbell" configuration. Smaller and less prominent foci of increased signal also were present on corresponding T2-weighted images. These lesions did not exhibit mass effect, edema, or enhancement with gadolinium-DTPA. They were not visible on CT (performed in two patients) and demonstrated no progression during a 2-year interval in three patients. Their signal characteristics and morphology suggest that they represent heterotopias containing Schwann cells and/or melanin deposits. Migrational abnormalities of these neural crest derivatives are known to occur in neurofibromatosis, and the presence of such heterotopias has been documented pathologically in patients with this disorder. While recent reports discuss foci of increased signal intensity on T2-weighted MR images in patients with neurofibromatosis, signal abnormalities on T1-weighted images have not yet been described. When lesions characterized by similar signal as well as morphologic characteristics are encountered on MR, the diagnosis of neurofibromatosis should be considered.

Adolescent↗

Distribution of somatostatin immunoreactivity in the forebrain of the squirrel monkey: basal ganglia and amygdala.

The distribution of somatostatin immunoreactivity in the basal ganglia and amygdala of the squirrel monkey (Saimiri sciureus) was studied with specific polyclonal antibodies directed against somatostatin-28 and somatostatin-28(1-12). Both antibodies gave similar results with regard to the distribution of somatostatin-immunoreactive neuronal profiles. A moderately dense and highly heterogeneous network of somatostatin-positive fibers was observed throughout the striatum. A dorsoventral gradient of increasing immunoreactivity was noted in the striatum and the caudate nucleus was found to strain generally less intensely than the putamen. The immunoreactive fibers within the striatum were mostly thin and varicose and formed patches corresponding to the striosomes, as visualized on adjacent sections immunostained for calbindin. Although some somatostatin cell bodies rimmed the striosomes, most of the positive cells were rather uniformly scattered in the striatum. These medium-sized cells were significantly smaller in the caudate nucleus (93 microns2, S.D. = 26 microns2) than in the putamen (122 microns2, S.D. = 39 microns2), but their density was significantly higher in the caudate nucleus (29.7 cells/mm2, S.D. = 8.8 cells/mm2) than in the putamen (20.5 cells/mm2, S.D. = 7.0 cells/mm2). The nucleus accumbens stained moderately and positive cell bodies were evenly dispersed throughout this structure. In contrast, the olfactory tubercle displayed a heavily stained neuropil but positive neurons were encountered only in its polymorph layer. In the sublenticular region, dense fiber plexuses appeared in register with nonreactive cell clusters of the nucleus basalis of Meynert and of the nucleus of the anterior commissure. More caudally, a dense bundle of positive fibers was observed at the level of the ansa lenticularis, the inferior thalamic peduncle, and the adjoining bed nucleus of the stria terminalis. Several fibers contributing to this bundle were of the woolly type. Woolly fibers also coursed in the substantia innominata between the ventral aspect of the globus pallidus and the optic tract, and ascended in the internal medullary lamina separating the internal and external segments of the globus pallidus. Somatostatin-immunoreactive cell bodies were uniformly scattered throughout the substantia innominata. The various nuclei of the amygdala showed a wide range of immunoreactivity. The central nucleus was lightly reactive, whereas the intercalated masses displayed a moderate staining. A dorsoventral gradient of immunostaining was noted in the ventrolateral portion of the amygdala, the lateral nucleus being moderately to densely stained and the basal nucleus very lightly to lightly immunoreactive.(ABSTRACT TRUNCATED AT 400 WORDS)

Amygdala↗

Basal ganglia motor control. II. Late pallidal timing relative to movement onset and inconsistent pallidal coding of movement parameters.

1. We have tested the hypothesis that the basal ganglia initiate some one or several modes of movement by recording the change in discharge frequency of pallidal neurons during visually triggered step and visually paced ramp moves in relation to the visual stimulus onset, the change in the electromyograph (EMG), and the movement onset of trained rhesus monkeys. 2. The modal times of change for globus pallidus pars interna (GPi) were significantly later than those for forearm agonist muscle EMG. By contrast, the modal time of change for the cerebellar dentate nucleus preceded that for wrist agonist EMG. 3. The direction of change in discharge frequency of the GPi cells was for 71% an increase and for 29% a decrease. 4. Because of the relatively late change of activity of GPi neurons, we propose that GPi neurons cannot initiate these movements, as others have also suggested. The commands for the initiation of these movements may instead be generated by structures that include the lateral cerebellum and the anterior cerebral cortex. 5. We have also tested the hypothesis that the pallidum of the basal ganglia or the dentate of the lateral cerebellum may control the direction and other parameters of the trajectory by recording from both structures to see whether cell discharge correlated with the parameter and whether the correlation was consistent across tasks. Two rhesus monkeys were trained to perform hold-ramp-hold and hold-step-hold visually guided movements in opposite directions by flexing and extending the wrist with and against uniform oppositely directed torque loads (0.2 Nm). Wrist position, velocity, force, and EMG were recorded simultaneously. Movement amplitudes and directional intent were computed and inferred, respectively. 6. Task related neurons were classified as follows: 1) directional, if the discharge rate was reciprocal for opposite movements or if it increased or decreased during movement in one direction only; 2) bidirectional, if the discharge rate increased or decreased during movement in both directions; and 3) "other," if it was directional under one load and bidirectional under the other. During step tracking, 34 GPi, 47 globus pallidus pars externa (GPe), and 44 cerebellar dentate nuclear neurons were related to the task. Of the GPi cells, 14 (41%) were directional, 6 (18%) bidirectional, and 14 (41%) other. Of the GPe neurons, 13 (28%) were directional, 19 (40%) bidirectional, and 15 (32%) other. Of the dentate cerebellar nuclear cells, 5 (11%) were bidirectional, 31 (70%) bidirectional, and 8 (18%) other.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Neurotensin receptor binding levels in basal ganglia are not altered in Huntington's chorea or schizophrenia.

Autoradiographic techniques were used to examine the distribution and levels of neurotensin receptor binding sites in the basal ganglia and related regions of the human brain. Monoiodo ([125I]-Tyr3)neurotensin was used as a ligand. High amounts of neurotensin receptor binding sites were found in the substantia nigra pars compacta. Lower but significant quantities of neurotensin receptor binding sites characterized the caudate, putamen, and nucleus accumbens, while very low quantities were seen in both medial and lateral segments of the globus pallidus. In Huntington's chorea, the levels of neurotensin receptor binding sites were found to be comparable to those of control cases. Only slight but not statistically significant decreases in amounts of receptor binding sites were detected in the dorsal part of the head and in the body of caudate nucleus. No alterations in the levels of neurotensin receptor binding sites were observed in the substantia nigra pars compacta and reticulata. These results suggest that a large proportion of neurotensin receptor binding sites in the basal ganglia are located on intrinsic neurons and on extrinsic afferent fibers that do not degenerate in Huntington's disease.

Adult↗

Methionine-enkephalin and substance P in the basal ganglia of normals, Parkinson patients, Huntington patients, and schizophrenics. A qualitative immunohistochemical study.

The distribution of methionine-enkephalin (ME)-like and substance P (SP)-like immunoreactivity in the basal ganglia of untreated schizophrenics as compared with normal control cases, and untreated Huntington and Parkinson patients was studied using the unlabeled peroxidase-antiperoxidase (PAP) method. ME but not SP was reduced in the pallidum of one of six schizophrenics. The remaining five cases showed no differences to the controls. In contrast, no or only very faint homogeneously distributed ME and SP was found in any part of the basal ganglia in Huntington's disease. In Parkinson's disease, SP immunoreactivity was within normal range.

Adult↗

[Relations between the basal ganglia and the thalamus of the primate. New morphologic data. New physiopathologic interpretations].

Considerable progress has been made over the last few years in our knowledge of the thalamus and basal ganglia and their relationships to the cerebral cortex. More detailed topographic studies in the macaque have demonstrated the separation, in the lateral region of the thalamus, between afferent cerebellar and basal ganglia territories. These territories fail to correlate with the subdivision between ventral and dorsal elements or the limits of a single cytoarchitectonic nucleus. The cerebellar territory corresponds to VIL (or VPLo) which projects towards the primary cortex, and to VIM (or area X) and DI (or VLc) which project towards premotor cortex. The nigral (and tectal) territory corresponds to VOM (or VAmc) and to some parts of the medial nucleus and projects mainly towards the oculomotor area, supplementary motor area and prefrontal cortex. In return, the oculomotor area and substantia nigra project towards the colliculus superior. Several thalamic nuclei constitute the pallidal territory: VOL (or VLo) projects mainly towards supplementary motor area, LPo (or VApc) and Do towards the prefrontal cortex. The median center, which receives afferents from pallidum and motor cortex, projects towards the striatum but also the motor cortex. The parafascicular nucleus projects towards the striatum and premotor cortex. It is still not possible to transpose data acquired in the macaque to man, but functional reinterpretations are possible. A system which involves the median pallidum, VOL and supplementary motor area could control motor initiative and flow of movement. A second system, involving the substantia nigra, colliculus superior, thalamic relay and oculomotor area could control posture. The pallidum and substantia nigra, anterior part of lateral mass, medial nucleus and prefrontal cortex could elaborate motor programmes.

Animals↗

Timing and prediction the code from basal ganglia to thalamus.

When is an inhibitory synapse not inhibitory? In this issue of Neuron, Person and Perkel demonstrate that thalamic neurons can translate extrinsic GABAergic input from the basal ganglia into highly precise patterns of sustained spiking in a circuit that is essential for vocal learning in songbirds. Postinhibitory rebound serves as a mechanism that preserves precise spike timing information, enabling reliable propagation of activity throughout this pathway. The results have broad implications for basic mechanisms of functional processing in both thalamus and basal ganglia and serve to increase our understanding of how acoustic units of vocal sounds are transformed into motor gestures during the sensitive period for song learning.

Animals↗

Basal ganglia choline levels in depression and response to fluoxetine treatment: an in vivo proton magnetic resonance spectroscopy study.

We have investigated proton magnetic resonance spectra of the basal ganglia in 41 medication-free outpatients with major depression, prior to starting an 8-week standardized trial of open-label fluoxetine, and 22 matched comparison subjects. Upon completing the trial, depressed subjects were classified as treatment responders (n = 18) or nonresponders (n = 23), based on changes in the Hamilton Depression Rating Scale. Depressed subjects had a lower area ratio of the choline resonance to the creatine resonance (Cho/Cr) than comparison subjects. This statistically significant difference between the depressed subjects and comparison subjects was more pronounced in the treatment responders than in the nonresponders. There were no differences in the relative volumes of gray matter or white matter in the voxel used for proton spectroscopy in depressed subjects relative to comparison subjects. These results are consistent with an alteration in the metabolism of cytosolic choline compounds in the basal ganglia of depressed subjects and, in particular, those who are responsive to fluoxetine.

Adult↗

Genetics, haloperidol, and the Fos response in the basal ganglia: a comparison of the C57BL/6J and DBA/2J inbred mouse strains.

The haloperidol-induced increase of Fos-like immunoreactive (Fos-li) neurons in the basal ganglia was compared in the C57BL/6J (B6) and DBA/2J (D2) inbred mouse strains. The D2 strain is 10-fold more sensitive than the B6 strain to haloperidol-induced catalepsy, a putative animal model of the extrapyramidal symptoms (EPS) seen after the administration of typical neuroleptics. In contrast, the strains are equally sensitive to the haloperidol facilitation of prepulse inhibition of the acoustic startle response, a measure of drug efficacy on the mesolimbic dopamine system. The haloperidol effects on Fos-li neurons were examined over the range of 0.1 to 6.0 mg/kg; the ED50s for haloperidol-induced catalepsy are 0.4 and 3.8 mg/kg in the D2 and B6 strains, respectively. In neither the core or shell of the nucleus accumbens nor the caudate-putamen (including the dorsolateral aspect) did the D2 strain show a greater Fos response compared to the B6 strain. In fact, in the dorsolateral caudate-putamen, the B6 strain showed a modest but significantly greater Fos response. However, at the output nuclei of the basal ganglia, the entopeduncular nucleus (EP) and the substantia nigra zona reticulata (SNr), the D2 strain consistently showed a greater Fos response. These data suggest that the EP and SNr may be important to understanding the difference in haloperidol-induced catalepsy between the D2 and B6 strains.

Animals↗

A new dynamic model of the cortico-basal ganglia loop.

An important issue in the neural control of posture and movement is how motor-related areas of the cerebral cortex modulate the activity of the output nuclei of the basal ganglia. In this chapter, the functional significance of the 'hyperdirect' cortico-subthalamo-pallidal pathway is emphasized, and further a new dynamic model of basal ganglia function is presented. When a voluntary movement is about to be initiated by cortical mechanisms, a corollary signal is conveyed through the 'hyperdirect' pathway to first inhibit large areas of the thalamus and cerebral cortex that are related to both the selected motor program and other competing programs. Next, another corollary signal is sent through the 'direct' cortico-striato-pallidal pathway to disinhibit this second pathway's targets, and ensure activation of only the selected motor program. Finally, a third corollary signal is sent through the 'indirect' cortico-striato-external pallido-subthalamo-internal pallidal pathway to strongly inhibit this third pathway's targets. This sequential information processing ensures that only the selected motor program is initiated, executed and terminated at the appropriate times, whereas other competing programs are canceled.

Animals↗

On the expression of Fos-like protein in the subthalamic nucleus and basal ganglia output systems following kainic acid injections into the rodent striatum.

By immunohistochemistry, Fos-like protein induced in response to intrastriatal kainic acid injections was explored in the basal ganglia and the ventrolateral thalamic nucleus of the rat. In the globus pallidus, entopeduncular nucleus, substantia nigra pars reticulata, subthalamic nucleus and ventrolateral thalamic nucleus, Fos was expressed in neuronal cell nuclei showing the maximal number at 4 h and disappeared within 48 h. The substantia nigra pars compacta neurons lacked prominent Fos induction, suggesting that a different mechanism may operate for changes of dopamine systems. Concurrent Fos expression noted in selected regions suggests the link of relay and output stations of the basal ganglia with the ventrolateral thalamus at the early stage of striatal cell degeneration.

Animals↗

Germinoma located in the basal ganglia in an 8-year-old girl.

CASE REPORT: The authors describe a unique case of an 8-year-old girl with a germinoma located in the left basal ganglia. Medical history begins 5 months before with a central diabetes insipidus, loss of weight (5 kg at admission), vomiting and asthenia. Computed tomography (CT) and cranial magnetic resonance imaging (MRI) are performed and demonstrate a left basal ganglia tumour (nucleus lentiformis). Diabetes insipidus is considered as non-visible germinoma localization on the pituitary stalk rather than as a possible consequence of peri-tumoural oedema surrounding the hypothalamus. Spinal MRI is normal. Neurological as well as general examination is normal. DISCUSSION: The first hypothesis is low-grade glioma, but pathological examination following a stereotactic biopsy of the lesion reveals a cerebral germinoma. A few days before the biopsy, the girl experienced a mild left facial palsy, and CT scans at the time of biopsy reveals an intra-tumoural haemorrhage. Alpha fetoprotein and human chorionic gonadotrophin were negative as blood and cerebrospinal fluid markers, whereas placental alkaline phosphatase was positive on immunohistochemical profile of the tumour samples. Dedicated chemotherapy, followed by focal irradiation (40 Gy, 30 sessions, 45 days; SIOP CNS GCT 93 protocol), is performed with a complete response. The outcome is good (Glasgow Outcome Scale=I), without any cognitive impairment and the persistence of a mild facial palsy and a slight right arm dystonia on last neurological examination. There is still no evidence of tumour recurrence.

Antineoplastic Agents↗

Immunohistochemical study of the serotoninergic innervation of the basal ganglia in the squirrel monkey.

A specific antibody raised against 5-hydroxytryptamine (5-HT) conjugated to bovine serum albumin was used to study the serotoninergic innervation of the basal ganglia in the squirrel monkey (Saimiri sciureus). At midbrain level, numerous fine 5-HT-immunoreactive axons were seen to arise from the immunopositive neurons of the dorsal raphe nucleus and less abundantly from those of the nucleus centralis superior. The bulk of these axons formed a rather loosely arranged bundle that arched ventrorostrally through the central portion of the midbrain tegmentum and ascended toward the ventral tegmental area. Several fascicles detached themselves from this bundle to reach the substantia nigra where they arborized into a multitude of heterogeneously distributed 5-HT terminals. The 5-HT innervation was particularly dense in the pars reticulata but much less so in the pars compacta of the substantia nigra. More rostrally other 5-HT fibers swept dorsolaterally and formed a remarkably dense network of varicose fibers within the subthalamic nucleus. A multitude of 5-HT axons continued their ascending course within the lateral hypothalamic area, and many of them swept laterally to invade the lenticular nucleus. At pallidal levels, the 5-HT axons arborized much less profusely in the external segment than in the internal segment, which contained numerous 5-HT varicose fibers and terminals arranged in a typical bandlike pattern. At striatal levels, the 5-HT terminals were particularly abundant in the ventral striatum, including the nucleus accumbens and deep layers of the olfactory tubercle. They also abounded in the ventrolateral region of the putamen and the ventromedial aspect of the caudate nucleus. Overall, the number of 5-HT fibers and terminals decreased progressively along the rostrocaudal axis of the striatum and several large and elongated zones rather devoid of 5-HT immunoreactivity were visualized, particularly in the caudate nucleus and the dorsal putamen. These zones of poor 5-HT immunoreactivity were in register with similar areas devoid of tyrosine hydroxylase immunoreactivity as seen on contiguous sections. These findings reveal that all the core structures of the basal ganglia in primates receive a significant serotoninergic input, but that the densities and patterns of innervation vary markedly from one structure to the other.

Afferent Pathways↗

Immunocytochemical studies of substance P and Met-enkephalin in the basal ganglia and substantia nigra in Huntington's, Parkinson's and Alzheimer's diseases.

Immunocytochemical studies of the distribution and intensity of Substance P and Met-enkephalin staining in the basal ganglia and substantia nigra were carried out in five cases each of brains from patients with Huntington's disease, Parkinson's disease, Alzheimer's disease, and normal controls. The usefulness of the peroxidase-antiperoxidase method for human autopsy material was confirmed. Substance P and Met-enkephalin fibers were distributed in essentially the same pattern as described in experimental animals and in human brains. In Huntington's disease brains decreased Substance P staining was found in the internal globus pallidus and the substantia nigra, in agreement with radioimmunoassay studies by others. Met-enkephalin staining in the external globus pallidus was of normal intensity, although present within a shrunken area. In Parkinson's and Alzheimer's diseases there was intense immunoreactivity for Substance P in the globus pallidus and substantia nigra, and for Met-enkephalin in the globus pallidus, at variance with reported decreases in Parkinson's disease by radioimmunoassay, but in essential agreement with other immunocytochemical studies. Immunocytochemical methods complement radioimmunoassays of human brain and may help in mapping neuropeptidergic pathways and in pinpointing abnormalities in these pathways in basal ganglia disorders.

Aged↗