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P Barone

Publications and source records attributed to P Barone.

At least 91 records · Page 5Linked to original sources

Prefrontal cortex and spatial sequencing in macaque monkey.

1. Single neuron activity was recorded from the prefrontal cortex of two macaque monkeys during the performance of a task involving spatial sequencing. The monkeys faced a panel displaying a central fixation point and three fixed targets (two lateral and one above the point of fixation). In the first phase of each trial, the three targets were turned on in random order: in the second phase, the animal had to press each target, still lighted, in the order of their illumination. Thus, successful performance of the task depended strongly on temporal memory. The animals were fitted with DC-EOG electrodes. 2. Three hundred and two task-related neurons were recorded in the superior arcuate area and caudal part of sulcus principalis. Among the cells whose pattern of activity appeared to be related to the sequencing task, five classes were distinguished: Visual tonic (VT), fixation, context, saccade related and visual phasic cells. In addition, a small number of cells appeared to be related to other aspects of the behavior, but not to the sequencing task. Our present analysis concentrates on two groups of sequencing task-related cells (VT and context cells). 3. The VT cells (35/302-11.5%) were recorded exclusively from the superior arcuate area. All VT cells increased their firing rate (sustained activation) during fixation of the central fixation point (FP) following onset of one of the three targets used, specific for a given cell (directional or spatial selectivity). In one group of VT cells, a shift in the eye position towards the specific peripheral target resulted in the return of the cells' firing rate to the pre-trial level. In the other group of VT cells, reset of the firing rate to pre-trial level was not related to the onset of fixation of the peripheral target. Sustained activation of the VT cells depended also on the sequential order of illumination of the specific target (temporal selectivity). In twenty-four cells (68.5% of VT cells) sustained activation was observed when the target came first in the sequence. Onset of the target in the second or third rank elicited either no response or only a short lasting phasic activation. In the remaining eleven cells (31.5% of VT cells), sustained activation was only observed when the target came second in a given sequence. The firing of the VT cells was correlated with the animals' performance of the task.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Haloperidol- and SCH23390-induced dopaminergic supersensitivities are not additive in the rat.

The effect of chronic D-1 and/or D-2 dopamine receptor blockade on apomorphine-induced behaviors was studied in rats treated for 21 days with the selective D-1 antagonist SCH23390, the predominantly D-2 antagonist haloperidol, and the combination of the two drugs at the same daily doses (0.1 and 1 mg/kg respectively). Apomorphine (0.3 mg/kg) 4 days following the last injection of the drugs increased (49-70%) stereotypic behavior in all animals as compared to saline-treated controls. Although the SCH23390-induced increase was lower than haloperidol-induced supersensitivity, stereotypies after combined administration of both drugs did not differ significantly from either, suggesting that the effects of the two drugs are not additive. Underlying receptor changes and modified D-1/D-2 receptor interactions may account for the participation of both receptor subtypes to the development of neuroleptic-induced dopaminergic supersensitivity.

Animals↗

Comparison of electrocardiographic data (P waves): test of a shape-based approach.

We tested a method for comparing ECG signals (P waves), in a sample of 10 normal males. In each subject, sets of 219 body surface ECGs were simultaneously recorded during tidal respiration. Only beats at end expiration and peak inspiration were considered. The beats of each group were subdivided into two subgroups of the same size (about 30 beats) and separately averaged. The two averaged beats at end expiration, assumed to be equal, were compared in order to estimate the noise variance (sigma2), i.e., the lowest value of variance at which the beats were statistically similar (P less than 0.05). At the same value of sigma2, the beat at end expiration significantly differed from that at peak inspiration. By considering the individual leads, significant differences were found in more than 50% of the 219 ECGs, in specific thoracic areas. The data indicated that the method can reveal differences between P waves occurring during tidal respiration and provide information on the topographical distribution of the differences.

Adult↗

On the optimal choice of the electrode number and locations in body surface mapping.

The problem of choosing the number and the thoracic locations of the leads needed for reconstructing body surface maps of heart potentials is considered. In a previous work (P. Barone, In "Computers in Cardiology" (K. L. Ripley, Ed.), pp. 491-494. IEEE Computer Soc. Press, Washington, DC, 1985) the problem was solved, provided that the user is able to give a threshold below which the information content of two leads is considered equal. In this paper a sensitivity analysis that can help the user in choosing the optimal threshold, or, equivalently, the optimal number of leads, is performed. The problem is reduced to the dynamic search of spanning forests of an undirected graph. An example using real data is also discussed.

Algorithms↗

Role of the dorsolateral prefrontal cortex in organizing visually guided behavior.

Unit activity was recorded in the prefrontal cortex of rhesus monkeys during performance of a delayed task with two motor responses, a saccade and an arm movement, to a complex pattern of auditory and visual stimuli. The peculiarity of the paradigm was that onset of the different sensory stimuli, orienting saccade and arm movement, were dissociated in time and occurred at prefixed time intervals. Two hundred and sixteen task-related units were recorded. The data show that the dorsolateral part of the prefrontal cortex plays a crucial role in temporal organization of visually guided behaviour. This cortical area contains the neural substrate of an encoding strategy for remembered or current events and objects in the behavioural surround that are not, as yet, foveated. This encoding mechanism subserves a particular cognitive process. Whether events or objects are, or are not, encoded depends on their significance for future behaviour. While foveation deletes their neural trace, it activates a class of cells that appear involved in the preparation of arm movements towards the foveated region. The destruction of these two complementary mechanisms would disrupt the organism's capacity to integrate temporally and spatially discontinuous information for performance of goal-directed acts.

Animals↗

D-1 dopamine agonist administration reduces the threshold for convulsions produced by pilocarpine.

Focal, limbic seizures were produced by systemically administered pilocarpine (200 mg/kg, i.p.); as previously described this dose produces limbic stereotypies but neither convulsions nor seizure-related brain damage. The pretreatment, 5 minutes prior pilocarpine, with the D-1 agonist SKF 38393 (-ED50 = 1 mg/kg; i.p.) induced convulsions similar to those produced by a higher, convulsant dose of pilocarpine. On the other hand, the pretreatment with the D-2 agonist LY 171555 failed to induce convulsions. The D-1 receptor antagonist SCH 23390 prevented the convulsions induced by SKF 38393 plus pilocarpine (200 mg/kg). This study indicates that D-1, but not D-2, receptor stimulation converts subconvulsant doses of pilocarpine into convulsant ones.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Supersensitivity to a D-1 dopamine receptor agonist and subsensitivity to a D-2 receptor agonist following chronic D-1 receptor blockade.

The effect of chronic D-1 dopamine (DA) receptor blockade on D-1 DA receptors and DA-mediated behaviors was studied in rats with unilateral, quinolinic acid-induced striatal lesions. Administration of the selective D-1 antagonist SCH 23390 for 15 days increased D-1 receptor numbers in the unlesioned striatum as indicated by [125I]SCH 23982 binding; ipsilateral turning initiated by the D-2 receptor agonist LY 171555 decreased, while grooming produced by the D-1 receptor agonist SKF 38393 intensified. There was, however, no change in the ability of the D-1 agonist to potentiate D-2 agonist-mediated rotation. The observed behavioral subsensitivity in response to a D-2 agonist may reflect D-1 receptor upregulation and the consequent imbalance of D-1/D-2 receptor interactions in the striatum where these two receptor subtypes appear to play opposite functional roles; potentiation of grooming, primarily a D-1 receptor-mediated behavior, may also reflect the increase in D-1 receptor numbers.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

A recursive algorithm to compute the baseline drift in recorded biological signals.

Baseline estimation and removal is one of the main problems to overcome in order to obtain a correct interpretation of recorded biological signals. The method described in this paper is based on a new application of recursive estimation of a smoothing spline, selected to model the unknown baseline. Its advantages over conventional methods derive from these characteristics: it is parametric and recursive, it works in the time domain, and the same software can be used in different applications, since no a priori frequency knowledge is needed. In the example, the method is applied to ECG recordings and a spectral analysis is thereby shown.

Algorithms↗

The D1 dopamine receptor in the rat brain: quantitative autoradiographic localization using an iodinated ligand.

The distribution of dopamine D1 receptors in the rat, labeled with [125I]SCH 23982, was studied using a quantitative in-vitro light-microscopic autoradiographic method. The binding of [125I]SCH 23982 to slide-mounted tissue sections and membrane preparations of prefrontal cortex was saturable, specific and of high affinity. Scatchard analysis revealed a Kd of 1.15 +/- 0.47 nM and Bmax of 8.76 +/- 0.34 fmol/mg tissue in prefrontal cortex membranes and a Kd of 1.27 +/- 0.14 nM and Bmax of 67.6 +/- 3.75 fmol/mg tissue in slide-mounted tissue sections at the level of the striatum. [125I]SCH 23982 was found to predominantly label D1 receptors, but a small fraction of the binding was to serotonin receptors. D1 receptors were found throughout the forebrain and were concentrated in the substantia nigra pars reticulata, accumbens nucleus, caudate putamen, entopeduncular nucleus, olfactory tubercle and the major island of Calleja. [125I]SCH 23982 binding to serotonin receptors was concentrated in the cortices, dorsal raphe, central gray, anterior hypothalamic area and the molecular cell layer of the cerebellum. Knowledge of the distribution of D1 receptors may increase our understanding of the role of D1 receptors in central nervous system dopaminergic function. Furthermore, data on the potential sites of interaction of [125I]SCH 23982 with serotonin receptors may help to understand the complex physiology and pharmacology of the primarily D1 selective compound.

Animals↗

Newer data on the configuration and variability ranges of body surface maps in a sample of normal subjects.

Quantitative data on the normal variability of body surface maps (BSM) are scarce in the literature. This is one of the reasons why BSM are not yet widely used in clinical practice despite their superior information contents. In this study we determined the average value and variability of a number of parameters derived from BSM in a group of 36 normal adult males, ages 22 to 60. Forty to 60 homogeneous beats were averaged for each subject. This enabled us to extend our study to the low voltage intervals (P,PQ,ST,U) which encompass more than 60% of the entire P-U duration and to contribute new data to controversial issues, such as the presence of two simultaneous maxima during atrial excitation. The following parameters were measured: a) the coordinates of the absolute potential maximum and minimum on the chest surface during the entire cardiac cycle; b) the time course of four voltage-related functions, namely: highest instantaneous potential value on the chest surface, lowest (most negative) potential, highest potential difference, and surface integral of the absolute value of the potential function. In recent studies these parameters were shown to be of considerable value in discriminating normal subjects from different categories of cardiac patients.

Adult↗

5-Hydroxytryptamine stimulates two distinct adenylate cyclase activities in rat brain: high-affinity activation is related to a 5-HT1 subtype different from 5-HT1A, 5-HT1B, and 5-HT1C.

5-HT binding sites of the 5-HT1 type are heterogeneous and appear to comprise several subtypes (5-HT1A, 5-HT1B and 5-HT1C); their physiological role is as yet unclear. The stimulation of adenylate cyclase induced by 5-HT has been investigated in membrane fractions prepared from rat brain cortex. Enzymatic activity was determined by measuring cAMP production with an HPLC technique. It was shown that 5-HT stimulates adenylate cyclase activity with 2 activation constants (Kact): one shows a high apparent affinity (Kact = 0.8 nM) and the other a lower apparent affinity (Kact = 0.30 microM). The latter activity, induced by micromolar concentrations of 5-HT, was inhibited by spiperone at concentrations that block 5-HT1A binding. 5-Methoxytryptamine, bufotenin, and LSD also had a stimulatory biphasic effect on adenylate cyclase activity, whereas trifluoromethylphenylpiperazine, 5-carboxyamidotryptamine, 8-hydroxy-(2-di-n-propylamino)tetralin, RU 24969 had a monophasic effect. Enzyme activation by drugs acting in the micromolar range was inhibited by spiperone (1 microM), suggesting a link between this activation and 5-HT1A sites. On the other hand, the high-affinity activation of the enzyme induced by 5-HT, 5-methoxytryptamine, bufotenin, LSD, and the activation induced by TFMPP were not inhibited by spiperone (1 microM), by propranolol (3 microM), or by mesulergine (0.1 microM), which selectively block 5-HT1A, 5-HT1B, and 5-HT1C sites. Inhibition was produced by dihydroergotamine, methysergide, cinanserin, and mianserin, but not by naloxone, phenoxybenzamine, and phentolamine. Therefore, these activations seem related to 5-HT1 receptors but not to 5-HT1A, 5-HT1B, or 5-HT1C sites. Accordingly, binding of [3H]5-HT to 5-HT1-like sites was examined in the presence of spiperone (1 microM) and propranolol (3 microM); in these conditions, a high-affinity site (KD = 3.4 nM) was indeed revealed. The relative potencies of a series of drugs that stimulate or inhibit the activation of the adenylate cyclase with a high affinity and their ability to inhibit this binding of [3H]5-HT showed a positive correlation, strongly suggesting a direct relation between this recognition site for 5-HT and the production of a second messenger (cAMP). Moreover, this potential receptor is shown to be heterogeneously distributed within the brain, and was localized postsynaptically at serotonergic synapses.

Adenylyl Cyclases↗

Attenuation of D-1 antagonist-induced D-1 receptor upregulation by concomitant D-2 receptor blockade.

The effect of chronic selective D-1 and/or D-2 dopamine receptor blockade on regional D-1 receptor binding was studied in rat brain following chronic treatment with the specific D-1 antagonist SCH 23390 and/or the predominantly D-2 antagonist haloperidol. D-1 receptor density and affinity were evaluated by quantitative autoradiography using 125I-SCH 23982. Chronic SCH 23390 treatment increased D-1 receptor density by 30 to 40% in the striatum, accumbens and tuberculum olfactorium; receptor affinity remained unchanged. Haloperidol had no effect on D-1 receptor Bmax or Kd values, although, when administered with SCH 23390, reduced the D-1 receptor upregulation induced by the D-1 antagonist in striatum and tuberculum olfactorium, but not in nucleus accumbens. These results may be attributable to D-1/D-2 dopamine receptor interactions occurring in the striatum and tuberculum olfactorium and may have implications for the prevention and treatment of drug-induced extrapyramidal disorders.

Animals↗

D-1 dopamine receptor changes after striatal quinolinic acid lesion.

Regional changes in the distribution of D-1 dopamine receptors produced by unilateral striatal lesions were evaluated in rat brain by quantitative autoradiography. Lesions were induced by local infusion of quinolinic acid, an endogenous excitotoxin that destroys intrinsic neurons, but spares fibers of passage. D-1 receptor density, as determined by [125I]SCH 23982 binding, was reduced in caudate-putamen, globus pallidus, substantia nigra, nucleus entopeduncularis on the lesioned side. These results confirm the presence of D-1 receptors on striatal cell bodies and provide direct evidence for the existence of presynaptic D-1 receptors on the terminals of striatal projections.

Animals↗

Prefrontal unit activity during a delayed oculomotor task in the monkey.

1. Unit activity was recorded in the prefrontal cortex of Rhesus monkeys during performance of a delay task with two motor components, an ocular saccade and an arm movement, following a complex pattern of auditory and visual stimuli. A special feature of the paradigm was that onsets of the different sensory stimuli, orienting saccade and arm movement were dissociated in time at predetermined time intervals. 216 task-related units were recorded. Discussion of the data focuses on two groups of cells the activity of which is modified by the saccade: the signal-related pre-saccadic tonic cells and the post-saccadic tonic cells. 2. Activity of signal-related pre-saccadic tonic cells was initiated with the onset of peripheral stimuli, visual and/or auditory, and terminated with an orienting saccade. Spatial selectivity was a feature of most units. They seemed to encode the region of space cued by the stimulus. 3. Many units were visually responsive. Activation of these depended both upon retinal locus of the stimulus and the requirement they imposed on subsequent behavior. Termination of their activity demanded foveation of some visual targets, not necessarily the one which had initiated their response. 4. The majority of these signal-related pre-saccadic tonic cells responded to onset of auditory stimuli. The termination of tonic activity in these cells with foveation of the region in space from which the signal originated suggests a spatial memory process that is no longer used when the visual fixation response can signal equivalent spatial information.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

Selective D-1 dopamine receptor agonist treatment of Parkinson's disease.

Preclinical evidence suggests that the D-1 dopamine receptor contributes to the generation of behaviors used as models for human extrapyramidal disorders. To evaluate the potential of D-1 receptor stimulation in neurologic disease, SKF 38393, a selective D-1 dopamine receptor agonist, was administered to seven patients with idiopathic Parkinson's disease in a double-blind, placebo controlled study. SKF 38393 was found to be rapidly absorbed when administered orally, and to occur in micromolar concentrations in spinal fluid. No change in scores of parkinsonian severity were noted when SKF 38393 was administered alone, or when the drug was combined with intravenous levodopa. The results support the view that the pathophysiology of Parkinson's disease may relate exclusively to the D-2 subclass of dopamine receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Novel data analysis for synchronised spontaneous neuromagnetic activity.

A novel approach to neuromagnetic data analysis is presented. This technique is aimed at studying synchronised spontaneous activity (SSA) and has been used to resolve two different signals from one single evoked response, providing evidence for two possibly distinct sources. The data presented are consistent with a model that permits the generators of spontaneous activity to be synchronised by sensory stimuli.

Brain↗