Flexible versus Fixed Spatial Self-Ordered Response Sequencing: Effects of Inactivation and Neurochemical Modulation of Ventrolateral Prefrontal Cortex.

Previously, studies using human neuroimaging and excitotoxic lesions in non-human primate have demonstrated an important role of ventrolateral prefrontal cortex (vlPFC) in higher order cognitive functions such as cognitive flexibility and the planning of behavioral sequences. In the present experiments, we tested effects on performance of temporary inactivation (using GABA receptor agonists) and dopamine (DA) D2 and 5-HT2A-receptor (R) blockade of vlPFC via local intracerebral infusions in the marmoset. We trained common marmosets to perform spatial self-ordered sequencing tasks in which one cohort of animals performed two and three response sequences on a continuously varying spatial array of response options on a touch-sensitive screen. Inactivation of vlPFC produced a marked disruption of accuracy of sequencing which also exhibited significant error perseveration. There were somewhat contrasting effects of D2 and 5-HT2A-R blockade, with the former producing error perseveration on incorrect trials, though not significantly impairing accuracy overall, and the latter significantly impairing accuracy but not error perseveration. A second cohort of marmosets were directly compared on performance of fixed versus variable spatial arrays. Inactivation of vlPFC again impaired self-ordered sequencing, but only with varying, and not fixed spatial arrays, the latter leading to the consistent use of fewer, preferred sequences. These findings add to evidence that vlPFC is implicated in goal-directed behavior that requires higher-order response heuristics that can be applied flexibly over different (variable), as compared with fixed stimulus exemplars. They also show that dopaminergic and serotonergic chemomodulation has distinctive effects on such performance.SIGNIFICANCE STATEMENT This investigation employing local intracerebral infusions to inactivate the lateral prefrontal cortex (PFC) of the New World marmoset reveals the important role of this region in self-ordered response sequencing in variable but not fixed spatial arrays. These novel findings emphasize the higher order functions of this region, contributing to cognitive flexibility and planning of goal directed behavior. The investigation also reports for the first time somewhat contrasting neuromodulatory deficits produced by infusions of dopamine (DA) D2 and 5-HT2A receptor (R) antagonists into the same region, of possible significance for understanding cognitive deficits produced by anti-psychotic drugs.

Trait Anxiety Mediated by Amygdala Serotonin Transporter in the Common Marmoset.

High trait anxiety is associated with altered activity across emotion regulation circuitry and a higher risk of developing anxiety disorders and depression. This circuitry is extensively modulated by serotonin. Here, to understand why some people may be more vulnerable to developing affective disorders, we investigated whether serotonin-related gene expression across the brain's emotion regulation circuitry may underlie individual differences in trait anxiety using the common marmoset (Callithrix jacchus, mixed sexes) as a model. First, we assessed the association of region-specific expression of the serotonin transporter (SLC6A4) and serotonin receptor (HTR1A, HTR2A, HTR2C) genes with anxiety-like behavior; and second, we investigated their causal role in two key features of the high trait anxious phenotype: high responsivity to anxiety-provoking stimuli and an exaggerated conditioned threat response. While the expression of the serotonin receptors did not show a significant relationship with anxiety-like behavior in any of the targeted brain regions, serotonin transporter expression, specifically within the right ventrolateral prefrontal cortex (vlPFC) and most strongly in the right amygdala, was associated positively with anxiety-like behavior. The causal relationship between amygdala serotonin levels and an animal's sensitivity to threat was confirmed via direct amygdala infusions of a selective serotonin reuptake inhibitor (SSRI), citalopram. Both anxiety-like behaviors, and conditioned threat-induced responses were reduced by the blockade of serotonin reuptake in the amygdala. Together, these findings provide evidence that high amygdala serotonin transporter expression contributes to the high trait anxious phenotype and suggest that reduction of threat reactivity by SSRIs may be mediated by their actions in the amygdala.SIGNIFICANCE STATEMENT Findings here contribute to our understanding of how the serotonin system underlies an individual's expression of threat-elicited negative emotions such as anxiety and fear within nonhuman primates. Exploration of serotonergic gene expression across brain regions implicated in emotion regulation revealed that serotonin transporter gene expression in the ventrolateral prefrontal cortex (vlPFC) and most strongly in the amygdala, but none of the serotonin receptor genes, were predictive of interindividual differences in anxiety-like behavior. Targeting of amygdala serotonin reuptake with selective serotonin reuptake inhibitors (SSRIs) confirmed the causal relationship between amygdala serotonin transporter and an animal's sensitivity to threat by reversing expression of two key features of the high trait-like anxiety phenotype: high responsivity to anxiety-provoking uncertain threat and responsivity to certain conditioned threat.

Trajectories and Milestones of Cortical and Subcortical Development of the Marmoset Brain From Infancy to Adulthood.

With increasing attention on the developmental causes of neuropsychiatric disorders, appropriate animal models are crucial to identifying causes and assessing potential interventions. The common marmoset is an ideal model as it has sophisticated social/emotional behavior, reaching adulthood within 2 years of birth. Magnetic resonance imaging was used in an accelerated longitudinal cohort (n = 41; aged 3-27 months; scanned 2-7 times over 2 years). Splines were used to model nonlinear trajectories of grey matter volume development in 53 cortical areas and 16 subcortical nuclei. Generally, volumes increased before puberty, peaked, and declined into adulthood. We identified 3 milestones of grey matter development: I) age at peak volume; II) age at onset of volume decline; and III) age at maximum rate of volume decline. These milestones differentiated growth trajectories of primary sensory/motor cortical areas from those of association cortex but also revealed distinct trajectories between association cortices. Cluster analysis of trajectories showed that prefrontal cortex was the most heterogenous of association regions, comprising areas with distinct milestones and developmental trajectories. These results highlight the potential of high-field structural MRI to define the dynamics of primate brain development and importantly to identify when specific prefrontal circuits may be most vulnerable to environmental impact.

Orbitofrontal dopamine depletion upregulates caudate dopamine and alters behavior via changes in reinforcement sensitivity.

Schizophrenia is associated with upregulation of dopamine (DA) release in the caudate nucleus. The caudate has dense connections with the orbitofrontal cortex (OFC) via the frontostriatal loops, and both areas exhibit pathophysiological change in schizophrenia. Despite evidence that abnormalities in dopaminergic neurotransmission and prefrontal cortex function co-occur in schizophrenia, the influence of OFC DA on caudate DA and reinforcement processing is poorly understood. To test the hypothesis that OFC dopaminergic dysfunction disrupts caudate dopamine function, we selectively depleted dopamine from the OFC of marmoset monkeys and measured striatal extracellular dopamine levels (using microdialysis) and dopamine D2/D3 receptor binding (using positron emission tomography), while modeling reinforcement-related behavior in a discrimination learning paradigm. OFC dopamine depletion caused an increase in tonic dopamine levels in the caudate nucleus and a corresponding reduction in D2/D3 receptor binding. Computational modeling of behavior showed that the lesion increased response exploration, reducing the tendency to persist with a recently chosen response side. This effect is akin to increased response switching previously seen in schizophrenia and was correlated with striatal but not OFC D2/D3 receptor binding. These results demonstrate that OFC dopamine depletion is sufficient to induce striatal hyperdopaminergia and changes in reinforcement learning relevant to schizophrenia.

Opposing effects of 5,7-DHT infusions into the orbitofrontal cortex and amygdala on flexible responding.

Central serotonin is implicated in a variety of emotional and behavioral control processes. Serotonin depletion can lead to exaggerated aversive processing and deficient response inhibition, effects that have been linked to serotonin's actions in the amygdala and orbitofrontal cortex (OFC), respectively. However, a direct comparison of serotonin manipulations within the OFC and amygdala in the same experimental context has not been undertaken. This study compared the effects of infusing the serotonin neurotoxin, 5,7-dihydroxytryptamine into the OFC and amygdala of marmosets performing an appetitive test of response inhibition. Marmosets had to learn to inhibit a prepotent response tendency to choose a box containing high-incentive food and instead choose a box containing low-incentive food, to obtain reward. OFC infusions caused long-lasting reductions in serotonin tissue levels, as revealed at postmortem, and exaggerated prepotent responses. In contrast, the significantly reduced prepotent responses following amygdala infusions occurred at a time when serotonin tissue levels had undergone considerable recovery, but there remained residual reductions in extracellular serotonin, in vivo. These opposing behavioral effects of serotonin manipulations in the same experimental context may be understood in terms of the top-down regulatory control of the amygdala by the OFC.

Laparoscopic ventral hernia repair during pregnancy.

BACKGROUND: Laparoscopic ventral hernia repair in comparison to open herniorrhaphy results in reduced length of stay, less post-operative pain, earlier return to work, and reduced complications for the repair of complex ventral hernias. The laparoscopic approach has been the standard of care for complex or large ventral hernias for non-pregnant patients over the past decade. Despite evidence that demonstrates that laparoscopy is safe during pregnancy, there is currently no consensus regarding the indications, contraindications, patient selection and post-operative care of pregnant patients evaluated for laparoscopic ventral herniorrhaphy. METHODS: The medical records of our pregnant patient who underwent laparoscopic ventral herniorrhaphy were reviewed for demographics, operative indications, surgical technique, perioperative complications, recurrence, and outcome of the pregnancy. A Medline search using the terms: laparoscopy, surgery, and pregnancy was performed to review the literature from 1997 to 2007. RESULTS: This case report represents the first published description of a safe and successful laparoscopic approach to the repair of a complex ventral hernia in a woman at 21 weeks gestation. The discussion reviews the current literature regarding the safety of laparoscopy in pregnant women and highlights techniques to reduce perioperative morbidity and risk to the fetus. CONCLUSIONS: Laparoscopic ventral hernia repair can be safe during pregnancy with appropriate fetal monitoring and consideration of physiologic changes that occur during parturition. Elective procedures should be delayed until after delivery and all semi-elective surgeries until organogenesis is completed during the second trimester.

The role of the orbitofrontal cortex and medial striatum in the regulation of prepotent responses to food rewards.

An impairment in learning to inhibit prepotent responses to positive stimuli is associated with damage to the orbitofrontal cortex (OFC) in rats, monkeys, and humans performing discrimination reversal, extinction, and detour reaching tasks. In contrast, a recent study showed that OFC-lesioned rhesus monkeys could learn to select the smaller of 2 quantities of food reward in order to receive the larger reward, at an equivalent rate to controls, despite the requirement to inhibit a prepotent response. Given this result, the aim of the present study was to further specify the contexts under which the OFC regulates responding and to identify additional components of limbic circuitry that contribute to such regulation. Marmosets with lesions of the OFC and medial striatum (MS), but not the amygdala, made more prepotent responses to a clear Perspex box containing high incentive food before learning to choose the box containing low incentive food, to obtain reward. However, having learned the incongruent incentive discrimination OFC- and MS-lesioned monkeys were impaired upon reversal of the reward contingencies, repeatedly selecting the previously rewarded low incentive object. These findings identify the critical contribution of the OFC and MS in the regulation of responding by affective cues.

Differential contributions of dopamine and serotonin to orbitofrontal cortex function in the marmoset.

We have shown previously that the inhibitory control functions of the orbitofrontal cortex (OFC) are disrupted by serotonin, but not dopamine depletions. However, both dopamine and serotonin terminals and receptors are present within the OFC and thus the aim of the present study was to determine the differential contributions of these neurotransmitters to orbitofrontal function. OFC and dopamine are involved in the process by which neutral stimuli take on reinforcing properties, by virtue of their prior association with reward, and guide behavior. Thus, we compared the performance of marmosets with dopaminergic or serotoninergic OFC depletions on a test of conditioned reinforcement. To further our understanding of serotonin in behavioral flexibility, the effect of these depletions was also compared on the extinction of a visual discrimination. Monkeys with serotonin depletions of the OFC displayed stimulus-bound responding on both tests of conditioned reinforcement and discrimination extinction suggesting that orbitofrontal serotonin plays a specific role in preventing competing, task irrelevant, salient stimuli from biasing responding. In contrast, monkeys with dopamine depletion were insensitive to conditioned reinforcers and displayed persistent responding in the absence of reward in extinction, a pattern of deficits that may reflect basic deficits in the associative processing of reward.

Uncoupling of behavioral and autonomic responses after lesions of the primate orbitofrontal cortex.

Successful adaptation to changes in an animal's emotional and motivational environment depends on behavioral flexibility accompanied by changes in bodily responses, e.g., autonomic and endocrine, which support the change in behavior. Here, we identify the orbitofrontal cortex (OFC) as pivotal in the flexible regulation and coordination of behavioral and autonomic responses during adaptation. Using an appetitive Pavlovian task, we demonstrate that OFC lesions in the marmoset (i) impair an animal's ability to rapidly suppress its appetitive cardiovascular arousal upon termination of a conditioned stimulus and (ii) cause an uncoupling of the behavioral and autonomic components of the adaptive response after reversal of the reward contingencies. These findings highlight the role of the OFC in emotional regulation and are highly relevant to our understanding of disorders such as schizophrenia and autism in which uncoupling of emotional responses may contribute to the experiential distress and disadvantageous behavior associated with these disorders.

Differential regulation of fronto-executive function by the monoamines and acetylcholine.

The prefrontal cortex (PFC) is innervated by the monoamines, dopamine (DA), noradrenaline (NA), and serotonin, as well as acetylcholine, and the marked influence of these neurochemical systems on prefrontal working memory processes has been widely described. However, their potentially, differential contribution to prefrontal functioning is less well understood. This paper reviews evidence to support the hypothesis that these neurochemical systems recruit distinct fronto-executive operations. Direct comparison of the effects of manipulations of these neuromodulators within PFC on performance of an attentional set-shifting paradigm reveals their differential contribution to distinct task stages. Depletion of prefrontal serotonin selectively disrupts reversal learning but not attentional set formation or set shifting. In contrast, depletion of prefrontal DA disrupts set formation but not reversal learning. NA depletion on the other hand specifically impairs set-shifting, whereas its effects on reversal learning remain unclear. Finally, depletion of prefrontal acetylcholine has no effect on either set formation or set shifting but impairs serial reversal learning. Because these neurochemical systems are known to represent distinct states of stress, arousal, attention, and affect, it is postulated that they augment the different types of executive operation that are recruited and performed within these states via a synergistic interaction with the PFC.

Synergistic and regulatory effects of orbitofrontal cortex on amygdala-dependent appetitive behavior.

This paper will review two avenues of our research in marmosets that have focused on the role of the orbitofrontal cortex (OFC) in amygdala-dependent appetitive behavior. The first demonstrates the important contribution of both the OFC and the amygdala to conditioned reinforcement (CRF). The second reveals the regulatory effects of the OFC on amygdala-dependent autonomic and behavioral arousal in appetitive conditioning. The process of CRF is one way in which an environmental cue can guide emotional behavior. As a consequence of its previous relationship with reward, a cue can take on affective value and reinforce behavior. Lesion studies in marmosets are described that show that CRF is dependent upon both the amygdala and OFC. The synergistic interactions between these structures that have been shown to underlie other aspects of reward processing are then considered with respect to CRF. The results are contrasted with those that show the importance of the OFC in suppressing positive affective responses elicited by the amygdala in response to a conditioned stimulus (CS). Specifically, it will be shown that the OFC is involved in the rapid suppression of conditioned autonomic arousal upon CS withdrawal and in the co-ordination of conditioned autonomic and behavioral responses when adapting to changing reward contingencies. It will be argued that, overall, the OFC plays a critical role in the context-dependent regulation of positive affective responding governed by external cues, in keeping with a role in executive control.

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.

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.

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.

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.

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.

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.

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.

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.