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Biomedical subjects

A C Roberts

Publications and source records attributed to A C Roberts.

At least 19 recordsLinked to original sources

Cognitive inflexibility after prefrontal serotonin depletion is behaviorally and neurochemically specific.

We have previously demonstrated that prefrontal serotonin depletion impairs orbitofrontal cortex (OFC)-mediated serial discrimination reversal (SDR) learning but not lateral prefrontal cortex (PFC)-mediated attentional set shifting. To address the neurochemical specificity of this reversal deficit, Experiment 1 compared the effects of selective serotonin and selective dopamine depletions of the OFC on performance of the SDR task. Whereas serotonin depletions markedly impaired performance, OFC dopamine depletions were without effect. The behavioral specificity of this reversal impairment was investigated in Experiment 2 by examining the effect of OFC serotonin depletion on performance of a modified SDR task designed to distinguish between 3 possible causes of the impairment. The results showed that the reversal deficit induced by prefrontal serotonin depletion was not due to a failure to approach a previously unrewarded stimulus (enhanced learned avoidance) or reduced proactive interference. Instead, it was due specifically to a failure to inhibit responding to the previously rewarded stimulus. The neurochemical and behavioral specificity of this particular form of cognitive inflexibility is of particular relevance to our understanding of the aetiology and treatment of inflexible behavior apparent in many neuropsychiatric and neurodegenerative disorders involving the PFC.

5,7-Dihydroxytryptamine↗

Selective prefrontal serotonin depletion impairs acquisition of a detour-reaching task.

We have recently shown that serotonin in the primate orbitofrontal cortex (OFC) contributes to the flexible control of behaviour. 5,7-dihydroxytryptamine-induced 5-HT depletions of OFC impair performance on a serial reversal discrimination task [Clarke et al. (2004)Science, 304, 878-880]. The deficit is characterized by perseverative responding to the previously rewarded stimulus, a deficit similar to that seen following lesions of the intrinsic neurones of the OFC [Dias et al. (1996)Nature, 380, 69-72]. The effect is neurochemically selective as dopaminergic lesions of the OFC, induced by 6-hydroxydopamine, have no effect [Clarke et al. (2006)Cerebral Cortex]. In order to test for the generality of the effect of serotonin on orbitofrontal processing and, in particular, its effects on flexible behaviour, the present study investigated the effects of serotonin depletions of OFC on performance of another task dependent upon an intact OFC, the detour-reaching task [Wallis et al. (2001)European Journal of Neuroscience, 13, 1797-1808]. Successful performance of this task requires inhibition of the animal's prepotent response tendency to reach directly along its line of sight to the reward. Compared with sham-operated controls, we found that lesioned monkeys made significantly more barrier reaches directly along their line of sight to the visible reward during task acquisition. This finding provides further support for the role of prefrontal serotonin in inhibitory control processes specifically in tasks sensitive to OFC dysfunction.

5,7-Dihydroxytryptamine↗

Primate orbitofrontal cortex and adaptive behaviour.

Orbitofrontal cortex contributes to behavioural adaptation in response to changes in the contingent relationship and incentive value of positive affective stimuli in the environment. This article integrates early descriptions of the effects of orbitofrontal ablation in monkeys, on object discrimination reversal and extinction, with contemporary theories of animal learning. Studies of incentive devaluation, conditioned reinforcement and changes in reward contingency are reviewed, highlighting the role of the orbitofrontal cortex in processing the affective and non-affective properties of rewarding stimuli, in reward expectation, and in goal selection. It is argued that future studies should focus on the interaction of the orbitofrontal cortex with peripheral arousal systems and the ascending monoamine systems in order to understand fully the role of the orbitofrontal cortex in behavioural adaptation.

Adaptation, Psychological↗

Prefrontal serotonin depletion affects reversal learning but not attentional set shifting.

Recently, we have shown that serotonin (5-HT) depletion from the prefrontal cortex (PFC) of the marmoset monkey impairs performance on a serial discrimination reversal (SDR) task, resulting in perseverative responding to the previously correct stimulus (Clarke et al., 2004). This pattern of impairment is just one example of inflexible responding seen after damage to the PFC, with performance on the SDR task being dependent on the integrity of the orbitofrontal cortex. However, the contribution of 5-HT to other forms of flexible responding, such as attentional set shifting, an ability dependent on lateral PFC (Dias et al., 1996a), is unknown. The present study addresses this issue by examining the effects of 5,7-dihydroxytryptamine-induced PFC 5-HT depletions on the ability to shift attention between two perceptual dimensions of a compound visual stimulus (extradimensional shift). Monkeys with selective PFC 5-HT lesions, despite being impaired in their ability to reverse a stimulus-reward association, were unimpaired in their ability to make an extradimensional shift when compared with sham-operated controls. These findings suggest that 5-HT is critical for flexible responding at the level of changing stimulus-reward contingencies but is not essential for the higher-order shifting of attentional set. Thus, psychological functions dependent on different loci within the PFC are differentially sensitive to serotonergic modulation, a finding of relevance to our understanding of cognitive inflexibility apparent in disorders such as obsessive-compulsive disorder and schizophrenia.

5,7-Dihydroxytryptamine↗

Acquisition of instrumental conditioned reinforcement is resistant to the devaluation of the unconditioned stimulus.

The associative mechanisms responsible for the efficacy of Pavlovian stimuli during first- and second-order conditioning have been extensively studied, but little is known about the representations underlying instrumental conditioned reinforcement. The present study investigated the associative structure underlying conditioned reinforcement, by employing an unconditioned stimulus (US) devaluation procedure on a commonly used instrumental task: the acquisition of a new response with conditioned reinforcement. Whilst US-directed behaviour was abolished following devaluation, the conditioned stimulus acting as a conditioned reinforcer supported the acquisition of instrumental responding. In this preparation then, the conditioned reinforcer appears to be impervious to devaluation of its associated US, suggesting that the underlying representation maintaining behaviour is independent of the current value of the US and may reflect the activation of a central appetitive motivational state.

Animals↗

Cognitive inflexibility after prefrontal serotonin depletion.

Serotonergic dysregulation within the prefrontal cortex (PFC) is implicated in many neuropsychiatric disorders, but the precise role of serotonin within the PFC is poorly understood. Using a serial discrimination reversal paradigm, we showed that upon reversal, selective serotonin depletion of the marmoset PFC produced perseverative responding to the previously rewarded stimulus without any significant effects on either retention of a discrimination learned preoperatively or acquisition of a novel discrimination postoperatively. These results highlight the importance of prefrontal serotonin in behavioral flexibility and are highly relevant to obsessive-compulsive disorder, schizophrenia, and the cognitive sequelae of drug abuse in which perseveration is prominent.

5,7-Dihydroxytryptamine↗

The role of the primate amygdala in conditioned reinforcement.

Conditioned reinforcement refers to the capacity of a conditioned stimulus to support instrumental behavior by acquiring affective properties of the primary reinforcer with which it is associated. Conditioned reinforcers maintain behavior over protracted periods of time in the absence of, and potentially in conflict with, primary reinforcers and as such may play a fundamental role in complex social behavior. A relatively large body of evidence supports the view that the amygdala (and in particular the basolateral area) contributes to conditioned reinforcement by maintaining a representation of the affective value of conditioned stimuli. However, a recent study in primates (Malkova et al., 1997), using a second-order visual discrimination task, suggests that the amygdala is not critical for the conditioned reinforcement process. In the present study, excitotoxic lesions of the amygdala in a new world primate, the common marmoset, resulted in a progressive impairment in responding under a second-order schedule of food reinforcement. In addition, the responding of amygdala-lesioned animals was insensitive to the omission of the conditioned reinforcer, unlike that of control animals, for which responding was markedly reduced. In contrast, lesioned animals were unimpaired when responding on a progression of fixed-ratio schedules of primary reinforcement. These data confirm that the amygdala is critical for the conditioned reinforcement process in primates, and taken together with other recent work in monkeys, these results suggest that the contribution of the amygdala is to provide the affective value of specific reinforcers as accessed by associated conditioned stimuli.

Acoustic Stimulation↗

Transient ovarian failure: a complication of uterine artery embolization.

OBJECTIVE: To report a case of transient ovarian failure shortly after arterial embolization for treatment of uterine fibroids, followed by recovery of ovarian function. DESIGN: Case report. SETTING: A university-based hospital. PATIENT: A 49-year-old woman with menorrhagia and anemia secondary to uterine fibroids and refractory to medical management. The follicle-stimulating hormone (FSH) level on cycle day 3 before the procedure was 8.2 mIU/mL. INTERVENTION(S): Bilateral uterine artery embolization for treatment of menorrhagia. MAIN OUTCOME MEASURE(S): Serum FSH level. RESULT(S): The patient developed amenorrhea and hot flashes 3 months after uterine artery embolization. Her serum FSH level at that time was 140.1 mIU/mL. Four months later, uterine bleeding resumed; her serum FSH level was 2.1 mIU/mL. CONCLUSION(S): Uterine artery embolization may hasten ovarian failure. This procedure should be reserved for women who have completed their child-bearing or are poor candidates for myomectomy. Patients should be counseled appropriately about the risk of possible ovarian failure.

Amenorrhea↗

Integral role of interventional radiology in the development of a pediatric liver transplantation program.

The aim of this study was to examine the role of interventional radiology (IR) in the pretransplant evaluation of potential living-related liver transplantation (LRLT) donors and in the post-transplant management of pediatric liver transplant recipients. Medical records and procedural reports were reviewed of 12 potential donors and five recipients for left lateral segment liver transplants. Procedures performed by the IR Division, clinical indications, and complications were tabulated. Retrospective calculation of radiation exposure to the skin and gonads of the donors and recipients were made. Three-dimensional ultrasound (3D US) was used in all 12 potential donors to screen for the donor with the most appropriately sized left lateral segment. The four optimal donor candidates underwent contrast angiography in order to measure the diameter and screen for variant arterial supply to the left lateral segment. Pretransplantation, one recipient underwent mesenteric angiography with indirect portography to confirm thrombosis of the portal vein and to prove patency of the splenomesenteric venous confluence. Three children underwent LRLT and two children received split livers from cadaveric donors. Thirty-two IR procedures were performed after transplantation (Tx) in the four transplant survivors (one child died following Tx). These IR procedures included: ultrasound-guided percutaneous liver biopsy to evaluate the pathologic cause of liver dysfunction (seven); placement of nasal jejunal feeding tubes (three) or a peripherally inserted central catheter (four) for nutritional and pharmacologic support; large-volume diagnostic and therapeutic paracentesis (two) and thoracentesis (one); percutaneous catheter drainage of symptomatic large pleural effusions (two), large-volume chylous ascites (one) (with later drain removal [one]), and a large biloma (one); percutaneous biliary drain placement (three), biliary drain replacement (two), and balloon cholangioplasty (four) to relieve obstructive jaundice from biliary enteric anatomic strictures; and mesenteric arteriography (one) for suspected thrombosis of the hepatic artery. No complications occurred. Mean skin and gonadal radiation doses were 193 mGy and 27 mGy, respectively, for donors, and 164 mGy and 60 mGy, respectively, for recipients. Even in a program such as this, with a limited series of pediatric liver Txs, it is apparent that IR plays an integral role in optimizing the clinical outcome and use of resources. Specific benefits included: selection of optimal donors; accurate mapping of the donor and occasionally recipient hepatic vasculature; and, most importantly, providing relatively safe minimally invasive procedures for nutritional support and diagnosis and management of untoward events after Tx. When possible, ultrasound guidance should be used to avoid excessive cumulative fluoroscopic exposure to recipients.

Adolescent↗

Dissociable contributions of the orbitofrontal and lateral prefrontal cortex of the marmoset to performance on a detour reaching task.

To gain insight into the nature and neural specificity of the relationship between simple problem solving, inhibitory control and prefrontal cortex, comparison of the effects of excitotoxic lesions of the orbitofrontal and lateral prefrontal cortex were examined on the performance of common marmosets on a detour reaching task. Monkeys were required to inhibit reaching directly for food reward in a transparent box and instead make a detour reach around to the side of the box either having had (i) no prior experience on the task (experiment 1) or (ii) previous experience in reaching around the sides of an opaque box (experiment 2). Whilst monkeys with orbitofrontal lesions had difficulty in inhibiting direct reaches to visible food reward (experiment 1), they could resist this prepotent response tendency following extensive prior experience of detour reaching with an opaque box (experiment 2). In marked contrast, monkeys with lateral prefrontal lesions exhibited no difficulty in inhibiting reaching to visible food reward or acquiring detour reaching per se (experiment 1). However, having been given the opportunity to acquire an efficient detour reaching strategy to hidden food reward these lateral prefrontal lesioned monkeys were impaired at transferring this strategy to the new context in which the food reward was made visible (experiment 2). This double dissociation between the effects of orbitofrontal and lateral prefrontal lesions on detour reaching provides evidence for a clear distinction in the level of control over responding exerted by the orbitofrontal and lateral prefrontal cortex, consistent with hierarchical ordering of response control processes within prefrontal cortex.

Animals↗

Coercion and drug treatment for postpartum women.

This research examined the extent to which various indicators of coercion were related to treatment retention in a gender-specific treatment program and a traditional outpatient program for pregnant and postpartum women who were mandated to enter treatment. Women who were given custody of their infant stayed in treatment longer than women who did not have custody. There was an interaction effect with women who had custody and were in the intensive day treatment program completing treatment at a much higher rate than those in the traditional program. Implications for social work professionals and policy makers are discussed.

Adolescent↗

Differential effects of 6-OHDA lesions of the frontal cortex and caudate nucleus on the ability to acquire an attentional set.

Evidence from both human and animal studies indicates that catecholamine (dopamine and noradrenaline) imbalances in the fronto-striatal circuitry are associated with deficits in higher- order cognitive functions. The present study examined how catecholamines within this circuitry modulate attentional function, specifically the ability to develop, maintain, and shift an attentional set. Catecholamine depletions within the frontal cortex of the common marmoset impaired the ability to acquire an attentional set, and increased susceptibility to distraction from task-irrelevant stimuli. Analysis of set-shifting performance with stimulus dimensions of varying salience suggested that frontal catecholamine depletion selectively disrupts "top-down", but not "bottom-up" attentional processing. In contrast, the ability to acquire and shift an attentional set remained intact following dopaminergic depletion from the caudate nucleus. However, the reduced susceptibility to distraction from task-irrelevant stimuli displayed by monkeys with dopaminergic depletions of the caudate nucleus suggests that responding was under more rigid control by the currently rewarded stimulus. The results demonstrate opposite behavioural effects of 6-hydroxydopamine (6-OHDA) lesions in the frontal cortex and caudate nucleus in tasks requiring selective attention. Frontal catecholamine depletion caused an increase in distractibility while caudate dopamine loss induced greater focusing of responding.

Adrenergic Agents↗

In-the-ear hearing aids within auricular prostheses.

We report a child with bilateral congenital microtia in whom cosmetic and auditory rehabilitation has been effected using in-the-ear hearing aids within prostheses overlying the rudimentary external auditory meati after canaloplasty. This novel method of auditory rehabilitation has not been reported before and is suitable in selected cases. The prostheses themselves were successfully secured using a prosthetic contact adhesive we have developed that offers excellent retention, little if any skin reaction, and high patient acceptability.

Audiometry, Evoked Response↗

Blood viscosity and hematological changes during prolonged submergence in normoxic water of northern and southern musk turtles (Sternotherus odoratus).

Musk turtles (Sternotherus odoratus) can survive at least 150 days of submergence in normoxic water at 3 degreesC, during which time there are large increases in packed cell volume (PCV). We investigated the effects of submergence in normoxic water at 3 degreesC on the blood viscosity of musk turtles from northern (Massachusetts) and southern (Alabama) locales. Blood was collected from air-breathing turtles and after 20, 50, 100, and 150 days of submergence in normoxic water at 3 degreesC. Hematological responses to submergence were similar in the two groups, therefore the results were combined. Packed cell volume increased steadily above that of controls after 20, 50, 100, and 150 days of submergence. Hemoglobin concentration also progressively increased above that of controls after 20, 50, and 100 days of submergence but declined to near control values after 150 days. Blood viscosity increased with increasing PCV; however, blood viscosity of musk turtles appears less affected by PCV than is blood viscosity of mammalian species. As such, musk turtles appear to be able to maintain adequate blood flow to tissues while increasing the oxygen carrying capacity of the blood during prolonged submergence. However, after 150 days submergence, oxygen delivery should decrease due to a reduced oxygen carrying capacity of the blood and an increased resistance to blood flow, which may limit the length of time these turtles can remain viable during hibernation.

Alabama↗

Preliminary experience with twenty perineal repairs using Indermil tissue adhesive.

OBJECTIVE: To assess the use of Indermil tissue adhesive for perineal repair. SETTING: Leeds General Infirmary, a teaching hospital with 4500 deliveries annually. METHOD: Over a period of five months, 20 women who sustained either a second degree tear or who had an episiotomy at vaginal delivery had their perineal skin repaired with Indermil tissue adhesive. They were followed up prior to discharge and then by telephone once discharged. RESULTS: Ten repairs followed normal vaginal deliveries, six were after ventouse deliveries, three after midcavity forceps delivery and one after a rotational forceps delivery. Three women noticed a burning sensation during application of adhesive. At follow up, 13 women were completely without problems, two complained of a sharp sensation from excess adhesive, one had silver nitrate applied at the six week check, two had small defects in the skin which healed well and in two women the skin edges broke down completely but did not need resuturing. CONCLUSION: Indermil tissue adhesive appears to be a safe and effective method of skin closure for episiotomies and second degree tears. The skin closure is quick and painless.

Delivery, Obstetric↗