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V J Brown

Publications and source records attributed to V J Brown.

At least 37 records · Page 2Linked to original sources
PubMed1997

On the relationships between the striatum and the pedunculopontine tegmental nucleus.

In this essay we consider the role of the pedunculopontine tegmental nucleus as a striatal output station. We review the relevant anatomical, electrophysiological, behavioral, and pathological studies and conclude that the pedunculopontine tegmental nucleus occupies an important position in striatal outflow, receiving motor output from the dorsal striatum and information from the ventral striatum relating to limbic processes of motivation and reinforcement. The hypothesis we present is that the pedunculopontine tegmental nucleus is at the very least an integral component of the limbic-motor interface, although in discussing this concept we also assess the likelihood that the limbic-motor interface is in fact a distributed system-that is, that limbic-motor interfacing is not all done by a single structure in the central nervous system but that different aspects of it are served by different systems. We present the hypothesis that the pedunculopontine tegmental nucleus is one critical site through which limbic information concerned with motivation, reinforcement, and the construction of novel associations can gain access to a stream of motor outflow coming from the caudate-putamen and directed toward pontomedullary systems without reference back to the cerebral cortex. This hypothesis is important because it highlights striatal outflow, which is not processed through the cortical re-entry systems, and also emphasizes the importance of pontine systems in cognitive processing.

Caudate Nucleus↗
PubMed1996

Covert orienting of attention in the rat and the role of striatal dopamine.

Attention can be directed to a location in the absence of overt signs of orienting, a phenomenon termed "covert orienting." The ability to orient attention covertly has been well documented in humans, but recent progress has been made with the operational definition of the processes involved in covert orienting. Reaction times to visual targets are quickened when attention is drawn to the location of the subsequent target, and processes such as disengagement, maintenance, and movement of attention can be dissociated by using this method. The possible involvement of striatal dopamine in covert orienting is disputed, with conflicting reports of deficits in covert orienting in patients with Parkinson's disease. To examine the significance of dopamine in the striatum in attentional processes, a test of covert orienting, analogous to that used in humans, was devised for the rat. Unilateral dopamine-depleting lesions of the striatum resulted in increases in mean reaction times contralateral to the side of the lesion, but reaction times did not change differentially as a function of the requirements to maintain, disengage, or shift attention. These findings add additional support to the hypothesis that the deficit that appears as hemineglect observed after striatal damage reflects a motor impairment rather than damage in neural systems underlying mechanisms for directing attention.

Animals↗
PubMed1996

The effect of systemic d-amphetamine on motor versus motivational processes in the rat.

This study examined the effects of systemic amphetamine in rats performing a reaction time task in which motivation and motor readiness were independently varied. Visual cues indicated the number of trials (one, two or three) needed before reinforcement was made available (i.e., reward cost). Lower reward cost was reflected in both a greater proportion of correctly completed trials and faster reaction times. Reaction times were also shorter as a function of increasing time from start of trial to the onset of the imperative stimulus (foreperiod), reflecting motor readiness or temporal probability summation. It was found that increasing dose of amphetamine resulted in faster reaction times, but the manner in which reaction time was speeded more closely resembled that of motor readiness than it did the speeding due to increasing motivation. Furthermore, the effects on performance of amphetamine and motivational condition were found to be entirely independent: there was no evidence to suggest that amphetamine enhanced, or disrupted, the expectation of forthcoming work or the response vigor which this engenders. It is concluded that systemic amphetamine does not act simply to amplify a natural reward signal. By contrast, amphetamine was found to enhance the effect of foreperiod, suggestive of a mechanism for the psychomotor stimulating effects of amphetamine.

Amphetamine↗
PubMed1996

Memory for the changing cost of a reward is mediated by the sublenticular extended amygdala.

The aim of this study was to examine the role of the sublenticular extended amygdala (SEA) in processes of reward and reinforcement. Previous studies have examined the effects of ibotenate lesions in this area on motivation for cocaine reward. In this study, animals were trained to work for sucrose pellets, rather than a drug, on a progressive-ratio schedule of reinforcement. Bilateral intracerebral infusions of ibotenic acid (lesion group) or vehicle (control group) were made into the SEA, following the same procedures as used in previous studies. After recovery from surgery, animals were tested for six sessions on the progressive ratio schedule. The lesion did not result in motivational impairments of the kind that have previously been reported: rather than decreases in breaking point (a measure of motivational strength), the lesion resulted in greater variability of breaking points, with a tendency for lesioned animals to work harder for reward than controls. The SEA-lesioned rats did not show the increase in postreinforcement pause that usually accompanies the increase in perceived work as the number of bar presses for a reward increases. Histological analyses showed that the ibotenate lesions had successfully destroyed the SEA and that damage was also present in adjacent structures. The results are interpreted in terms of a mnemonic, rather than a motivational, deficit.

Amygdala↗
PubMed1995

Discriminative cues indicating reward magnitude continue to determine reaction time of rats following lesions of the nucleus accumbens.

The role of the nucleus accumbens in incentive motivation is accepted but poorly understood. In this study, we examined in the rat one aspect of motivated behaviour which might be mediated by the nucleus accumbens, namely the translation of a motivational signal (the expected value of a reward) into motor output (responding for the reward). Rats were trained in a reaction time task in which on each trial they received one, two or three pellets. The number of pellets for each trial was randomly determined in advance and signalled to the rats by cue lights. Rats responded with faster reaction times as the size of the expected reward increased. Following ibotenic acid lesions of the nucleus accumbens, there was no difference in the pattern or the speed of reaction times. Although lesions of the nucleus accumbens did not disconnect the motivational system from the motor system, it is possible that the nucleus accumbens is involved in the learning of the incentive salience of external stimuli. Therefore, after postoperative testing the cue contingencies were reversed. Initially, the cues continued to be interpreted according to their prior significance, but eventually both the lesioned rats and the control group acquired the new relationship and did so in equivalent times. We conclude that the nucleus accumbens is not involved in the acquisition or expression of the processes whereby the expectation of rewards of different value is translated into a motor initiation signal.

Animals↗
PubMed1995

Responses of cells in the tail of the caudate nucleus during visual discrimination learning.

1. The tail of the caudate nucleus and adjacent ventral putamen (ventrocaudal neostriatum) are major projection sites of the extrastriate visual cortex. Visual information is then relayed, directly or indirectly, to a variety of structures with motor functions. To test for a role of the ventrocaudal neostriatum in stimulus-response association learning, or habit formation, neuronal responses were recorded while monkeys performed a visual discrimination task. Additional data were collected from cells in cortical area TF, which serve as a comparison and control for the caudate data. 2. Two monkeys were trained to perform an asymmetrically reinforced go-no go visual discrimination. The stimuli were complex colored patterns, randomly assigned to be either positive or negative. The monkey was rewarded with juice for releasing a bar when a positive stimulus was presented, whereas a negative stimulus signaled that no reward was available and that the monkey should withhold its response. Neuronal responses were recorded both while the monkey performed the task with previously learned stimuli and while it learned the task with new stimuli. In some cases, responses were recorded during reversal learning. 3. There was no evidence that cells in the ventrocaudal neostriatum were influenced by the reward contingencies of the task. Cells did not fire preferentially to the onset of either positive or negative stimuli; neither did cells fire in response to the reward itself or in association with the motor response of the monkey. Only visual responses were apparent. 4. The visual properties of cells in these structures resembled those of cells in some of the cortical areas projecting to them. Most cells responded selectively to different visual stimuli. The degree of stimulus selectivity was assessed with discriminant analysis and was found to be quantitatively similar to that of inferior temporal cells tested with similar stimuli. Likewise, like inferior temporal cells, many cells in the ventrocaudal neostriatum had large, bilateral receptive fields. Some cells had "doughnut"-shaped receptive fields, with stronger responses in the periphery of both visual fields than at the fovea, similar to the fields of some cells in the superior temporal polysensory area. Although the absence of task-specific responses argues that ventrocaudal neostriatal cells are not themselves the mediators of visual learning in the task employed, their cortical-like visual properties suggest that they might relay visual information important for visuomotor plasticity in other structures. (ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Dopamine dependent reaction time deficits in patients with Parkinson's disease are task specific.

This study tested the hypothesis that patients with Parkinson's disease are impaired when they must rely on internal information to generate a response. Choice reaction times of control subjects and patients with Parkinson's disease, on and off their medication, were measured in tasks in which the motor demands were constant but which varied in the degree to which the stimuli held intrinsic information about the required response. A dopaminergic deficit was observed only in the tasks which employed stimuli compatible with the response and not in a task employing stimuli arbitrarily associated with the response. The data do not support the hypothesis that patients are differentially impaired in using internalized stimulus-response relationships.

Adult↗
PubMed1993

Covert orienting of attention in macaques. I. Effects of behavioral context.

1. A task was used by Posner (1980) to measure shifts of attention that occurred covertly, in the absence of an eye movement or other orienting response. This paradigm was used here to assess the nature of covert attentional orienting in monkeys to develop an animal model for neurophysiological studies. Shifts of attention were measurable in monkeys and were consistent across a variety of experimental conditions. 2. The paradigm required that monkeys fixate and release a bar at the appearance of a target, which was preceded by a cue. Reaction times to targets that followed peripheral cues at the same location (validly cued) were significantly faster than those that followed cues in the opposite visual field (invalidly cued). This difference was defined as the validity effect, which as in humans, is used as the measure of a covert attentional shift. 3. When the proportion of validly to invalidly cued targets was decreased, no change was seen in the validity effect of the monkeys. This is in contrast to humans, for whom the ratio of validly to invalidly cued targets affected the magnitude of the validity effect. When 80% of the targets were preceded by cues at the same location, the validity effect was greatest. The effect was reversed when the proportions were reversed. From this result, it is concluded that cognitive processes can affect covert orienting to peripheral cues in humans, whereas in trained monkeys, performance was automatic. 4. To test whether cognitive influences on attention could be demonstrated in the monkey, an animal was taught to use symbolic, foveal signals to covertly direct attention. The magnitude of this validity effect was greater than that obtained with peripheral cues. 5. The effects of motivational and perceptual processes were tested. Although overall reaction times could be modified, the facilitating effects of the cues persisted. This constancy across motivational and perceptual levels supports the notion that the monkeys were performing the task in an automatic way, under the exogenous control of peripheral cues. 6. Most visual cuing has been tested with visual landmarks at the locations of cues and targets. These monkeys were trained with such landmarks, and when tested without them, the attentional effect of the cues was nearly abolished. These data suggest that local visual features can be important for covert orienting. 7. To determine the spatial extent of the effect of the cue, monkeys and humans were tested with four cue-target distances (0-60 degrees).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

Striatal graft-associated recovery of a lesion-induced performance deficit in the rat requires learning to use the transplant.

Peformance in a prelearned choice reaction time task was studied 6 months after surgery in rats with ibotenate-induced lesions of the striatum either with or without striatal grafts, and in sham-operated controls. The long postoperative interval allowed full transplant maturation and the establishment of appropriate connections by the transplants. The animals were trained prior to surgery on a visual choice reaction time task which requires that a movement is made away from stimuli signalling reward. The use of multiple measures allowed a thorough analysis of several aspects of the animals' performance. Whilst sham-operated control animals recovered normal (preoperative) performance rapidly, the lesioned animals had a severe performance deficit. Although the transplanted animals were initially at least as deficient in performance as the lesioned group, repeated testing led to an amelioration of the lesion-induced deficit according to two distinct measures of spatial bias and reaction time. On a third measure, latency to complete the lateralized movement, the grafted group were initially worse than the lesioned group but repeated testing resulted in significant recovery. These results suggest that postoperative training may help to optimize the efficacy of graft-induced recovery, and that animals may need to learn to use a transplant in order for it to confer functional benefit in complex prelearned tasks.

Journal Article↗
PubMed1992

Is calcium oxalate an adequate explanation for nonvisualization of breast specimen calcifications?

This study was initiated to determine whether the apparent calcium loss during histologic breast specimen processing could be explained by the presence of birefringent, transparent calcium oxalate crystals (type I). In previous investigations, the authors had noted a possible loss of 26.2% of calcium during the processing and sectioning of breast specimens. Two hundred thirteen histologic slides prepared from blocks demonstrating calcium radiographically but not histologically were reviewed with polarized light. An additional 506 slides from 19 malignancies appearing as microcalcifications were also reviewed with polarized light. Only one slide from each group (0.2% and 0.5% from the malignant and benign groups, respectively) demonstrated birefringent calcium oxalate (type I). Thus, the presence of calcium oxalate does not sufficiently explain the non-visualization of calcium, which is due instead to processing of breast specimens.

Biopsy↗
PubMed1991

Response-related deficits following unilateral lesions of the medial agranular cortex of the rat.

Rats with lesions of the medial agranular frontal cortex (AGm) were tested for sensorimotor function. Spatial response bias and reaction time to lateralized visual targets were recorded in an automated test of visual reaction time. The same rats were also tested for somatosensory capacity and on a skilled reaching task. In all tasks, there was an ipsilateral response bias but no evidence of sensory neglect. In the visual reaction time task, initiation time was lengthened bilaterally. These deficits may parallel the effects on motor function after unilateral frontal cortical lesioning in primates. The results support the hypothesis that rat AGm contains a homologue of primate secondary motor cortex.

Afferent Pathways↗
PubMed1991

Simple and choice reaction time performance following unilateral striatal dopamine depletion in the rat. Impaired motor readiness but preserved response preparation.

Rats were trained to perform a visual spatial discrimination, where stimulus luminance provided information regarding the required direction of response. The visual stimuli were presented either in advance of a temporally unpredictable auditory imperative stimulus (simple reaction time condition) or simultaneously with the imperative stimulus (choice reaction time condition). Following unilateral striatal dopamine depletion, produced by intracerebral infusion of 6-hydroxydopamine, there was not only a marked spatial response bias towards the side of the dopamine depletion but also an abolition of the delay-dependent speeding of reaction time that reflects motor readiness, on the side contralateral to the lesion. Nevertheless, the rats continued to show a benefit in performance of the simple reaction time condition compared with the choice reaction time condition, indicating that they were able to use advance information to select and prepare responses. The results are discussed in the context of differential deficits shown by patients with Parkinson's disease in simple versus choice reaction time performance, and of the functions of parallel corticostriatal loops subserving the normal control of action.

Animals↗
PubMed1991

Breast specimen microcalcifications: radiographic validation and pathologic-radiologic correlation.

A prospective analysis of specimens from location and biopsy of mammographically suspect microcalcifications in 108 patients was carried out to determine if microcalcifications were lost during histopathologic processing and the clinical relevance of such loss. Nine hundred sixty-eight paraffin blocks were prepared from 425 gross tissue slices containing calcifications identified at radiography of the specimens. Calcium was apparently lost both during preparation of the blocks (13.6%) and after slide preparation (12.6%), for a total possible loss of 26.2%. All specimens demonstrated calcification histologically. One pathology report was amended because of information obtained after recuts, but all cancers were detected on original slides whether or not calcifications were identified initially. The results indicate that, by following the suggestions offered to ensure adequate histopathologic sampling of calcification seen at mammography, most if not all of the calcification present can be detected on the original slide.

Breast↗
PubMed1989

Comparison of adrenal and foetal nigral grafts on drug-induced rotation in rats with 6-OHDA lesions.

Separate groups of rats with unilateral 6-OHDA lesions of the nigrostriatal pathway received intrastriatal foetal (E14) substantia nigra suspension grafts, intrastriatal postnatal (P22-25) adrenal medulla suspension grafts using either collagenase- or trypsin-based dissociation procedures, intraventricular adrenal medulla grafts, or remained with lesions alone. Rats with nigral or adrenal suspension grafts, but not rats with adrenal solid grafts, showed reduced apomorphine-induced rotation in comparison with lesion rats. The nigral graft group alone showed substantial reduction of amphetamine-induced rotation, and this was the only group manifesting good long-term graft survival. These results indicate that nigral and adrenal grafts do not have comparable mechanisms of functional action, and suggest that adrenal grafts can ameliorate apomorphine-induced rotation by a non-specific mechanism.

Adrenal Medulla↗
PubMed1989

Elementary processes of response selection mediated by distinct regions of the striatum.

The relative contributions of the medial and lateral caudate putamen to performance of a visual reaction time task were compared by examining the effects of unilateral ibotenate-induced lesions to these regions in the rat. Different groups of rats were trained to respond either towards (Discrimination 1) or away from (Discrimination 2) unpredictable, brief visual stimuli presented to either side of the head. Lateral striatal lesions produced a strong spatial bias towards the side of the lesion but left the latency for the initiation of responses to the visual cues unchanged. By contrast, the medial striatal lesions resulted in a smaller degree of spatial response bias but a significant slowing of initiation latency to the side contralateral to the lesion. These effects were irrespective of the side of the stimulus presentation and thus represent response-related impairments. The lesions were further dissociated in their effects on responding inappropriately to task requirements. These results demonstrate a double dissociation of behavioral effects of lateral and medial striatal damage that can be used to infer the operation of distinct elementary processes of response output within a single task. They are important not only in demonstrating functional effects of hypothetical segregated parallel corticostriatal loops but also in showing that these loops must interact to produce integrated performance.

Acetylcholinesterase↗
PubMed1989

Deficits in response space following unilateral striatal dopamine depletion in the rat.

Hungry rats were trained to report the occurrence and location of brief, unpredictable visual stimuli presented to the left of their heads in 1 of 2 response locations. After training, they received unilateral infusions of 6-hydroxydopamine, depleting dopamine throughout the head of the caudate putamen, either on the left or the right side, that is, either ipsilateral or contralateral to the side on which they were required to respond. Following an ipsilateral lesion there were no impairments in localization of the visual discriminanda and there was no lengthening of reaction time. The contralaterally lesioned rats, however, showed considerably lengthened reaction times to both stimuli and a profound bias to the nearer of the 2 response locations. Evidence from probe trials in which the visual stimuli were presented separately or simultaneously showed that the impairment was not due to a failure to localize the stimuli in contralateral space but, rather, resulted from a deficit in directing responses in contralateral space. It is suggested that this may be due to a distortion in the representation of response space.

Animals↗