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Biomedical subjects

J P Joseph

Publications and source records attributed to J P Joseph.

At least 19 recordsLinked to original sources

The effects of sequence structure and reward schedule on serial reaction time learning in the monkey.

This research tests the hypothesis that sequence learning performance in non-human primates will be modulated both by the structure of the sequences to be learned and by the schedule of reward applied during learning. Sequence learning in humans has been extensively explored with serial reaction time (SRT) protocols where learning is revealed by reduced reaction times for stimuli presented in repeating sequences vs. stimuli presented in random series. The SRT protocol has been used to demonstrate that different types of sequential structure may be learned under different awareness conditions. Here, we consider surface and abstract structure of sensorimotor sequences such that sequences ABCBAC and DEFEDF (where A to F correspond to spatial locations on a touch sensitive screen) have different serial order or surface structure, but share the same abstract structure 123213, and are thus considered isomorphic. In four experiments, we manipulated the type of sequential structure to be learned, and the schedule of reward in spatial sequence learning tasks. Both of the two monkeys tested demonstrated significant SRT learning for serial order or surface structure, while they failed to learn and transfer abstract structure. Their learning performance was also modulated by the schedule of reward. These results are in support of our hypothesis and are discussed in the context of existing models of sensorimotor sequence learning.

Animals↗

Anterior cingulate activity during routine and non-routine sequential behaviors in macaques.

Anterior cingulate cortex is important in monitoring action for new challenges. We recorded neuron activity in the anterior cingulate sulcus of macaques while they performed a sequential problem-solving task. By trial and error, animals determined the correct sequence for touching three fixed spatial targets. After the sequence was repeated three times, we then changed the correct solution order, requiring a new search. Irrespective of component movements or their kinematics, task-related neurons encoded the serial order of the sequence. Neurons activated with sequence components (68%) differed in activity between search and repetition. Search-related activity occurred when behavioral flexibility was required and ended as soon as the animal accumulated enough information to infer the solution, but had not yet tested it. Repetition-related activity occurred in a regime of memory-based motor performance in which attention to action is less necessary.

Animals↗

Problem solving and logical reasoning in the macaque monkey.

This study focuses on the performances of monkeys in a spatial problem-solving task that involves working memory. Two monkeys had to find, by trial-and-error, the touching order of 2 or 3 targets in a set of 3 or 4 fixed spatial targets. When a solution was found and performed 6 times, the order was changed and the animal had to resume a new search within the same set of targets. Thus, in a training session, many searches (up to 60) could be initialised. The data show that the animals conducted a methodical search for the hidden order and found the solution in a minimal number of trials. We conclude that the monkey is able to construct complex cognitive structures, similar to logical reasoning, to solve spatial problems of this type.

Animals↗

Activity in the caudate nucleus of monkey during spatial sequencing.

1. There are indications that the execution of behavioral sequences involves the basal ganglia. In this study we examined the role of the caudate nucleus in the construction, storage, and execution of spatial plans. 2. Two monkeys (Macaca mulatta) were trained to perform sequences of saccades and arm movements. The animals had to remember the order of illumination, variable from one sequence to another, of three fixed spatial targets. After a delay, they had to visually orient toward, and press each target in the same order. Six different sequences were executed on the basis of the order of illumination of the targets. Single cell activity was recorded from the four caudate nuclei of the two monkeys. 3. Neural activity was analyzed in each sequence during 10 different periods: the instruction period in which the targets were illuminated, the three orientation periods toward the different targets, the three postsaccadic periods, and the three periods of target pressing. Statistical comparisons were made to detect differences between the different sequences with respect to activity in each period (sequence specificity). 4. A total of 2,100 neurons were studied, of which 387 were task related. The task-related cells were found in both the head and the body of the caudate nucleus. 5. During central fixation, anticipatory activity (n = 81) preceded onset of specific events. Four groups were considered: 1) neurons (n = 46) anticipating offset of the central fixation point, 2) neurons (n = 7) anticipating the illumination of any target, regardless of its spatial position or order of presentation (rank), 3) neurons (n = 17) anticipating the illumination of the first target, regardless of its spatial position, and 4) neurons (n = 11) anticipating the illumination of a given target, regardless of its rank. 6. Phasic visual responses to target onset were observed in 48 cells. The cells responded primarily to the contralateral and upper targets. In a majority (n = 35), visual responses were modulated by the rank of the target(s). Many cells (n = 20) responded only if the corresponding target was first; other cells responded only if the target was second or if it had complex time relationships with the other targets. 7. The responses of the cells to the same instruction stimuli repeated twice in a row, and under the condition that the animal did not behaviorally use the first instruction in between, were tested. More than one-third of the tested cells (n = 14) did not respond, or responded very weakly, to the second instruction.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Neural activity in the caudate nucleus of monkeys during spatial sequencing.

Single cell activity was recorded from the monkey caudate nucleus. The animal had to execute motor and oculomotor sequences based on memorized information. In each trial, the monkey had to remember the order of illumination of three fixed spatial targets. After a delay, the animal had to press the targets in the same sequence. The "task-related" cells were activated by onset of the targets and on execution of saccades or arm movements. In a majority of cells, activation did not depend only on the retinal position of the stimuli or on the spatial parameters of gaze and arm movements, but was contingent on the particular sequence in which the targets were illuminated or the movements were performed.

Animals↗

Perforation of the globe--a complication of peribulbar anaesthesia.

Peribulbar anaesthesia has been recommended as a safer alternative to retrobulbar anaesthesia. We report a case of perforation of the globe sustained during peribulbar anaesthesia which resulted in blindness. Orbital injections are potentially dangerous, be they peribulbar or retrobulbar. To minimise the risk, short, blunt needles are advocated for the peribulbar route.

Aged↗

Chemotactic activity of aqueous humor. A cause of failure of trabeculectomies?

The chemoattractant activity for ocular fibroblasts of the aqueous humor of patients undergoing glaucoma surgery was evaluated in 48-well microchemotaxis chambers and compared with control specimens from patients undergoing cataract extractions. All specimens were chemoattractant, but those from patients who had previously undergone glaucoma surgery that had failed were of significantly greater activity than the controls'. This chemoattractant activity is primarily chemotactic. It consists of heat-stable and heat-labile components. The predisposition of a patient to sustain failed glaucoma drainage surgery may be related to the chemoattractant activity of his aqueous humor, since strongly chemoattractant aqueous humor may encourage fibrosis at the operation site.

Animals↗

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↗

Partial characterization of the fibroblast chemotactic constituents of human aqueous humour.

This study demonstrates that aqueous humour derived from patients undergoing cataract extraction contains chemoattractants for ocular fibroblasts. The chemoattractant activity is independent of the surgical approach to obtaining the specimen as well as the surgeon operating. Studies in rabbits demonstrate that the chemoattractant activity is not artefactually produced by aqueous sampling and confirm the integrity of the blood-aqueous barrier. Substances responsible for this activity have molecular weights greater than 30,000; they are deactivated by low pH but retain activity at high pH. Identification of the chemoattractants in aqueous humour may allow pharmacological manipulation of would healing in relation to trabeculectomies.

Aged↗

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↗

Taxol, cytochalasin B and colchicine effects on fibroblast migration and contraction: a role in glaucoma filtration surgery?

Migration and contraction are fibroblast activities in scar tissue formation which may contribute towards the failure of trabeculectomies. We attempted to modify the migration and contraction of Tenon's capsule fibroblasts in vitro using the drugs taxol, cytochalasin B and colchicine. Migration assays were conducted in 48-well micro-chemotaxis chambers, using rabbit aqueous humour which has been previously identified as a powerful chemoattractant for Tenon's fibroblasts, and fibronectin as the stimuli for migration. All three drugs inhibited the migration of fibroblasts to both fibronectin and aqueous humour, with maximal activity seen at 10(-6)M (taxol), 10(-5)M (cytochalasin B), and 10(-3) M (colchicine). In a single cell contractile assay in which contraction of whole fibroblasts was initiated with exogenous adenosine triphosphate (ATP), taxol and colchicine showed anticontractile activity, maximal at 10(-5)M and 10(-3)M respectively, but cytochalasin B was ineffective. The significance of the activities of these drugs in relation to their proposed use for improving the success of trabeculectomies is discussed.

Actins↗

The effect of retinoids on the migration of Tenon's capsule fibroblasts.

The effect of the retinoids, retinol and all-trans acid, was assessed in vitro on the migration of rabbit Tenon's capsule fibroblasts, with a view to using these drugs as inhibitors of fibrosis in relation to trabeculectomies. No inhibition of fibroblast migration was demonstrated, and in fact retinol significantly enhanced both the random and directed migration of these cells (p less than 0.001 and p less than 0.01, respectively). This study emphasises the importance of using appropriate cells when investigating the effects of drugs on wound healing.

Animals↗

Wound healing as a barrier to successful filtration surgery.

Trabeculectomy fails to control the intra-ocular pressure adequately in a proportion of patients. Approaches to solving this problem have involved modifications of surgery, histological studies of tissue from failed and functioning blebs, animal studies, and in vitro investigations of some of the basic processes of wound healing. This paper reviews the current state of investigations in these disciplines with particular reference to wound healing in this specialised site.

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↗

Normal rabbit aqueous humour, fibronectin, and fibroblast conditioned medium are chemoattractant to Tenon's capsule fibroblasts.

Some of the chemotactic and chemokinetic properties of rabbit Tenon's fibroblasts were examined in a 48-well micro-chemotaxis chamber. Normal rabbit aqueous humour, fibronectin, and fibroblast conditioned medium were used in the assay, and all were shown to be chemoattractant. In addition, aqueous humour was shown to be powerfully chemotactic. Since the failure of human trabeculectomies is associated with migration of fibroblasts to the operation site, the study of the chemoattractant influences acting on these cells may allow manipulation of their behaviour in order to influence favourably the outcome of surgery.

Animals↗

Visuomotor properties of neurons of the anterior suprasylvian gyrus in the awake cat.

Single cell activity was recorded from the Anterior Suprasylvian (ASS) gyrus of cats trained to orient their gaze toward visual or auditory stimuli. Sixty-five fixation cells were activated or suppressed as long as the animals were attentive to a particular region of space in the tangential or in the radial direction. Most of these fixation cells were neither light nor sound sensitive. Fifty-five cells were activated in relation to saccades. Fourteen neurons were active before and 41 after the onset of saccades. Nineteen neurons were also active with spontaneous eye movements in the dark. Fifteen neurons were seemingly related to vergence. They were not light-sensitive. They were preferentially activated by visual stimuli moving in the radial direction either towards or away from animal's face. Fifty light-sensitive neurons responded to moving stimuli. Only two neurons responded to onset of eccentric stationary light-stimuli. Fifty-one neurons showed a modulation in relation to vestibular stimulation. A majority showed, in addition, a vestibulo-collic response. These data suggest that the ASS gyrus in cats has a major role in the construction of the behavioral space.

Acoustic Stimulation↗

Activity of neurons in the cat substantia nigra pars reticulata during drinking.

Extracellular activity of single neurons in the pars reticulata of the Substantia Nigra (SNpr) was recorded in cats during drinking. Two groups of cells were distinguished: I. Somatosensory cells which responded by a short decrease in firing rate to the arrival of water against the upper lip. We suggest that these stimulus-related responses reflect a complex process linked to preparation of buccolingual movements. II. Action-related cells which were de-activated at the beginning or during the entire drinking period but without modulation in relation to the individual movements of jaws and tongue. We suggest that de-activation of these cells during drinking operates as a gating mechanism which allows implementation of complex motor sequences by cortical and/or subcortical structures.

Animals↗