Wilson's disease. Development of neurological disease after beginning penicillamine therapy.

Patients with neurological symptoms and signs of Wilson's disease have been frequently noted to have a worsening of their condition after beginning chelation therapy with D-penicillamine. Presymptomatic patients, however, are not expected to develop neurological manifestations once appropriate therapy is begun. We describe a patient who was seen with hepatic disease and no neurological symptoms who became neurologically incapacitated soon after beginning penicillamine therapy.

Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, "prefrontal" and "limbic" functions.

The central theme of the "segregated circuits" hypothesis is that structural convergence and functional integration occurs within, rather than between, each of the identified circuits. Admittedly, the anatomical evidence upon which this scheme is based remains incomplete. The hypothesis continues to be predicated largely on comparisons of anterograde and retrograde labeling studies carried out in different sets of animals.

Aberrant phosphorylation of neurofilaments accompanies transmitter-related changes in rat septal neurons following transection of the fimbria-fornix.

Lesions of the fimbria-fornix (FF) have been reported to cause retrograde changes in neurons of the medial septal nucleus (MSN). To analyze the nature and time course of these events, we investigated changes in cytoskeletal elements (phosphorylated and non-phosphorylated neurofilament (NF) proteins) and transmitter-related enzymes (choline acetyltransferase (ChAT) in MSN neurons following FF transection. During the first week postlesion, ChAT immunoreactivity and size of many perikarya were reduced.

Microphysiological recordings at CT gantry site during stereotactic thalamotomy.

Neural unit recording was performed during CT-guided stereotactic thalamotomy in 2 patients referred for severe cerebellar ataxia and dysmetric movements. Periodic CT scanning was performed during the recording in order to verify probe location and trajectory. Our experience with electrophysiological recordings at the CT gantry site demonstrates the feasibility of acquiring satisfactory neural unit recordings in spite of the high-voltage environment.

Topographic, non-collateralized basal forebrain projections to amygdala, hippocampus, and anterior cingulate cortex in the rhesus monkey.

Projections of the basal forebrain magnocellular complex to the limbic telencephalon of the primate were studied by combining double-retrograde tracing with immunocytochemistry. Tracers were injected into anterior cingulate cortex and hippocampus or into hippocampus and amygdala. Retrogradely labeled populations of neurons were topographically arranged but intermingled peripherally.

Fiber pathways of basal forebrain cholinergic neurons in monkeys.

In rhesus monkeys, autoradiographic tracing methods, complemented by immunocytochemical and histochemical techniques, were used to delineate pathways by which cholinergic neurons of the nucleus basalis of Meynert (nbM) and nucleus of the diagonal band of Broca (ndbB) project to forebrain targets. Following injections of [3H]amino acids into these nuclei, 5 major fiber pathways were identified: axons of the nbM and ndbB project medially, principally within the cingulum bundle, to dorsomedial portions of the hemispheres; nbM and ndbB fibers exit laterally beneath the pallidum and striatum, enter the external and extreme capsules, and pass within the corona radiata to terminate in lateral and caudal regions of neocortex; axons coursing ventrally from the nbM project to portions of the temporal lobe, including the amygdala; some fibers pass through the fibrae pass orbitofrontales to the orbitofrontal cortex; and, finally axons of the nbM/ndbB project via the fimbria/rornix and a ventral pathway to the hippocampus. The presence of these 5 radiolabeled pathways arising from basal forebrain cholinergic neurons was confirmed by acetylcholinesterase histochemistry and choline acetyltransferase immunocytochemistry.

The primate nucleus basalis of Meynert: neuronal activity related to a visuomotor tracking task.

The activity of neurons in the nucleus basalis of Meynert (nbM), both the compact (nbMc) and interstitial (nbMi) components, has been examined in monkeys trained to perform a visuomotor step-tracking task. This study was carried out in the same animals and with the same task used to examine neuronal activity in the external and internal segments of globus pallidus (GPe and GPi) and ventral pallidum (VP). The presumed interstitial cells that are located within the laminae surrounding GPe and GPi and identified physiologically by their similarity with nbMc neurons, are referred to as border cells.

The primate globus pallidus: neuronal activity related to direction of movement.

Neurons in the arm areas of the external and internal segments of the globus pallidus (GPe and GPi) and the ventral pallidum (VP) have been examined in a visuomotor step-tracking task. This task, which was similar to that used previously to examine neurons in the arm area of the putamen, dissociated the direction of movement from the pattern of muscle activity associated with the movement. The major finding of the present study is that, as in the putamen, the activity of almost half of the neurons in GPe and GPi was related to the direction of movement.

Magnetic resonance planned thalamotomy followed by X-ray/CT-guided thalamotomy.

Magnetic resonance imaging (MRI) is currently the optimal neuroradiologic technique for visualizing the anterior and posterior commissure for defining the AC-PC line. CT is the optimal technique for electrode and probe guidance during stereotactic thalamotomy. Various possibilities of transferring or overlying MRI and CT are outlined which in some future might result in more refined methods of CT-MRI guidance for stereotactic surgery.

Effects of scopolamine and physostigmine on recognition memory in monkeys with ibotenic-acid lesions of the nucleus basalis of Meynert.

Monkeys with bilateral ibotenic-acid lesions of the nucleus basalis of Meynert, an area rich in cholinergic neurons that innervate the cerebral cortex, were compared with unoperated control monkeys on a recognition memory task. Although animals with large lesions had substantial reductions of cortical choline acetyltransferase activity, none showed impairment in the task. Lesion effects were observed, however, when performance was assessed following administration of a muscarinic receptor blocker (scopolamine) or a cholinesterase inhibitor (physostigmine).

Nucleus basalis of Meynert neuronal activity during a delayed response task in monkey.

A total of 183 nucleus basalis of Meynert (NBM) neurons were recorded in a monkey performing a delayed response task. Significant changes in discharge rate were detected in 74% of the NBM cells sampled with most responses occurring in the choice (64%) or the reward (67%) epochs of the task. Neuronal responses in the cueing epoch were less common (31%) and less robust than in the choice epoch, although the animal made essentially the same arm movement in both cases.

Basal forebrain neurons provide major cholinergic innervation of primate neocortex.

In 3 monkeys, lesions were made in the basal forebrain by microinjections of ibotenic acid into the nucleus basalis. Bilateral samples of multiple neocortical gyri were assayed for the activity of choline acetyltransferase. Compared to control hemispheres, enzyme activity was reduced up to 69% in the neocortex ipsilateral to the lesion; in addition, acetylcholinesterase staining was decreased at the lesioned site and in the ipsilateral cortex.

Noncollateral projections of basal forebrain neurons to frontal and parietal neocortex in primates.

To test the hypothesis that axons of the basal forebrain cholinergic system collateralize to innervate widely separated areas of cortex, two distinct, retrogradely transported fluorescent dyes were injected into discrete neocortical regions of three macaques. In two monkeys, True Blue was injected into parietal cortex and Nuclear Yellow into frontal cortex; in a third monkey, placement of the dyes was reversed. Following these large (3-10 microliters total) injections, neurons single labeled with either Nuclear Yellow or True Blue were seen throughout most of the ipsilateral nucleus basalis of Meynert and nucleus of the diagonal band of Broca.

Microstimulation of the primate neostriatum. II. Somatotopic organization of striatal microexcitable zones and their relation to neuronal response properties.

Sensorimotor response properties of neostriatal neurons were characterized in conjunction with assessments of the motor effects of intrastriatal microstimulation in unanesthetized rhesus monkeys. Neuronal activity and microexcitability were assessed at 250- to 500-micron intervals and, in some cases, at 25- to 100-micron intervals. The results are based on the functional characterization of 878 putamen and 224 caudate neurons and analysis of the effects of microstimulation at each of these recording sites.

Microstimulation of the primate neostriatum. I. Physiological properties of striatal microexcitable zones.

Microstimulation was carried out at over 1,250 sites in the putamen in four unanesthetized rhesus monkeys. At numerous sites, microstimulation resulted in movements of individual body parts including leg, arm, and face. Microstimulation-evoked limb movements were invariably contralateral to the stimulating electrode.

Primate globus pallidus and subthalamic nucleus: functional organization.

Neuronal relations to active movements of individual body parts and neuronal responses to somatosensory stimulation were studied in the external (GPe) and internal (GPi) segments of the globus pallidus (GP) and the subthalamic nucleus (STN) of awake monkeys. In GPe (n = 249), GPi (n = 151), and STN (n = 153), 47, 29, and 28% of the cells, respectively, discharged in relation to active arm movements, 10, 11, and 15% to leg movements, and 22, 22, and 18% to orofacial movements. Of the neurons whose activity was related to arm movements, 26, 16, and 21% in GPe, GPi, and STN, respectively, discharged in relation to movements of distal parts of the limb.

Role of basal ganglia in limb movements.

Recent anatomic and physiologic studies have shed new light on the functional organization of the basal ganglia and their role in movement. The basal ganglia receive topographically organized input from the entire neocortex. Influences from sensorimotor and "association" cortices appear to remain segregated in the basal ganglia.

Single cell studies of the primate putamen. II. Relations to direction of movement and pattern of muscular activity.

The major goal of this study was to determine whether the activity of single cells in the primate putamen was better related to the direction of limb movement or to the underlying pattern of muscular activity. In addition, the neural responses to load application were studied in order to determine whether the same neurons were also responsive to somatosensory stimuli. Two rhesus monkeys were trained to perform a visuomotor arm tracking task which required elbow flexion/extension movements with assisting and opposing loads in order to dissociate the direction of elbow movement from the pattern of muscular activity required for the movement.

Single cell studies of the primate putamen. I. Functional organization.

In order to clarify the functional organization of the putamen and the nature of sensory inputs to this structure we studied the relation of single cell activity to active movements and somatosensory stimulation in the awake primate. Neurons (N = 707) were categorized on the basis of their relation to active movements or responses to sensory stimulation of individual body parts. 38% of neurons studied were related to the arm, 9% to the leg, 11% to the mouth or face, and 3% to axial portions of the body.

Functional organization of the basal ganglia: contributions of single-cell recording studies.

Studies of single-cell discharge in the basal ganglia of behaving primates have revealed: characteristic patterns of spontaneous discharge in the striatum, external (GPe) and internal (GPi) globus pallidus, pars reticulata and pars compacta of the substantia nigra, and the subthalamic nucleus (STN); phasic changes in neural discharge in relation to movements of specific body parts (e.g. leg, arm, neck, face); short-latency (sensory) neural responses to passive joint rotation; a somatotopic organization of movement-related neurons in GPe, GPi, and STN; a clustering of functionally similar neurons in the putamen and globus pallidus; greater representation of the proximal than of the distal portion of the limb; changes in neural activity in reaction-time tasks, suggesting a greater role of the basal ganglia in the execution than in the initiation of movement in this paradigm; a clear relation of neuronal activity to direction, amplitude (?velocity) of movement, and force; a preferential relation of neural activity to the direction of movement, rather than to the pattern of muscular activity.