Search

Objective: To determine the effect of 0.0005% chlorhexidine and tris-EDTA solution on the strength of three commonly used suture types for closure of equine ventral midline celiotomy., Study Design: Controlled laboratory study., Sample Population: Knotted loops (n = 10/group, 150 knot constructs total)., Methods: Strands of 2 polyglactin 910, 3 polyglactin 910, and 2 polydioxanone were tied to form knotted loops. All knotted loops were mounted on a tabletop force measurement machine system and loaded at 100 mm/min until the breaking force (N) was determined. The breaking force (N) of knotted loops using dry suture was recorded at study start, then of knotted loops soaked in either 0.0005% chlorhexidine and tris-EDTA for 20 min followed by incubation in equine serum (treatment) or serum alone (control) for 14 and 21 days. Analysis of variance (ANOVA) compared the breaking force between the treatment and control groups at each time point., Results: There was no significant difference in the breaking force of 2 USP polyglactin 910 (p = .35, confidence interval [CI] = -0.21-0.59), 3 USP polyglactin 910 (p = .61, CI = -0.41-0.24), or 2 USP polydioxanone (p = .76, CI = -0.63-0.46) soaked in 0.0005% chlorhexidine and tris-EDTA solution followed by equine serum when compared to each respective suture soaked in equine serum only., Conclusion/clinical Significance: Since 0.0005% chlorhexidine and tris-EDTA solution did not exhibit a significant effect on the breaking force of the absorbable sutures studied, the solution may be used for incisional lavage in the clinical setting., (© 2023 American College of Veterinary Surgeons.)

The study's objective was to evaluate the feasibility and dispersion of an open approach to the transversus abdominis plane (TAP) block in eight adult equine cadavers. A ventral midline incision was made, starting 2 cm cranial to the umbilicus and extending 25 cm cranially. In total, 0.5 mL/kg of new methylene blue (NMB) was injected per horse, divided into six injections. Using an 18 g, 8 cm Tuohy needle, three injections were made per side. The needle was guided blindly into the TAP using palpation. A 60 mL syringe was attached directly to the needle, depositing ~0.08 mL/kg at each site. The time to complete the injections was recorded for each cadaver. Following injection, the ventral body wall was dissected to determine if the dye was present within the TAP space as well as to measure the extent of the dispersion of the dye, the cranial to caudal extent, and the width of the dye's spread. Complete deposition of NMB into the TAP (six of six sites) was achieved in 5/8 horses. The median time needed to perform all the injections was 263 s. Increased adiposity (retroperitoneal fat) was associated with unsuccessful injections. This approach to the TAP was easily and quickly performed, though less successful in horses with increased retroperitoneal fat and increased BCS.

The following article provides an overview of the last 5 years of research and innovation within the field of equine colic surgery, focusing on new techniques, new or recently described lesions, prevention of lesion recurrence or postoperative complications, and updates in prognoses. Early surgical intervention is an important factor in horse survival., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Lower survival has been reported in foals than adults with small intestinal strangulating obstruction (SISO), but age-dependent outcomes have not been examined directly. Hospital records were collected from five US academic referral hospitals. It was hypothesized that foals would exhibit lower survival than case-matched adults. Foal cases 6-months-of-age or younger, and adult cases between 2- and 20-years-of-age were collected. Data revealed 24 of 25 (96.0%) foals and 66 of 75 (88.0%) adults that were recovered from surgery for SISO survived to hospital discharge. Sixteen of the total 41 (39.0%) foals studied were euthanized intraoperatively, whereas 30 of 105 (28.6%) adults were euthanized intraoperatively. Common lesions in foals that were recovered from surgery were volvulus ( n = 13) and intussusception ( n = 5), whereas common lesions in adults were volvulus ( n = 25) and strangulating lipoma ( n = 23). This study was limited by incomplete medical records, relatively small sample size, and lack of long-term follow-up. Unexpectedly, short-term survival tended to be higher in foals than adults and may have been partly driven by case selection prior to referral or surgery or decision-making intraoperatively. More optimism toward surgical treatment of foals with SISO may be warranted.

Background: Acute colitis is a serious cause of morbidity and death in horses. Recent studies have compared clinical features of coronavirus and salmonellosis, but no study has compared clinical features of enteric salmonellosis, coronavirus, and neorickettsiosis., Hypothesis/objectives: To identify risk factors for laminitis and nonsurvival to discharge in horses with enteric salmonellosis, coronavirus, or neorickettsiosis., Animals: Eighty-five horses hospitalized for acute colitis from 2011 to 2019., Methods: Retrospective case series. Medical record review (2011-2019) of adult (≥2 years) horses with colitis. Primary outcomes were laminitis and survival to discharge. Multivariable logistic regression was performed to assess association between variables and the development of laminitis. Stepwise Cox regression was performed to assess association between variables and survival., Results: Seventeen of 85 (20%) horses developed laminitis during hospitalization. Neorickettsiosis cases (11/26, 42%) were more likely to develop laminitis than coronavirus (0/16, 0%) cases (odds ratio [OR] 24.48; 95% confidence interval [CI]: 1.33-451.74, P = .03). There was no significant difference in laminitis between salmonellosis and neorickettsiosis cases (OR 0.27; 95% CI: 0.07-1.07, P = .06). Admission heart rate (OR 1.08; 95% CI: 1.02-1.15, P = .01), total solids (OR 0.17; 95% CI: 0.06-0.54, P = .003), band neutrophils (OR 1248.47; 95% CI: 6.62-235 540, P = .008), and bicarbonate concentration (OR 0.68; 95% CI: 0.5-0.92, P = .01) were predictive of development of laminitis during hospitalization. Sixty-three of 85 (74%) horses survived to discharge: 16/16 (100%) coronavirus cases, 17/26 (65%) neorickettsiosis cases, 14/20 (70%) salmonellosis cases, and 16/23 (70%) unknown cases. Packed cell volume (hazard ratio [HR] 1.17; 95% CI: 1.09-1.26, P < .001), L-lactate concentration (HR 1.33; 95% CI: 1.14-1.55, P < .001), and development of laminitis (HR 7.07; 95% CI: 1.67-29.95, P = .008) were retained in the final multivariable model for prediction of nonsurvival to discharge., Conclusion and Clinical Importance: Nonsurvival and laminitis rates were high, likely related to the presence of neorickettsiosis in the region., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Auscultation and ultrasonography are noninvasive techniques used to assess gastrointestinal motility in horses. Recently, noninvasive acoustic gastrointestinal surveillance (AGIS) biosensors evaluating intestinal motility have been validated in humans., Objectives: To compare AGIS to auscultation and ultrasonography for detecting decreased motility after xylazine administration., Study Design: Randomised, blinded, controlled cross-over proof of principle study., Methods: Six healthy horses were evaluated under fasted and nonfasted conditions and randomly assigned to receive treatment with 0.4 mg/kg xylazine or an equivalent volume of 0.9% NaCl intravenously. After a 48-h washout period, the process was repeated with the alternate treatment. Motility was assessed pre and posttreatment. Borborygmi were assessed in each abdominal quadrant and graded on a scale of 0-3, with 3 being continuous borborygmi. Duodenal, jejunal and caecal contractions were assessed ultrasonographically in consistent locations. Four AGIS biosensors were applied in standardised locations (duodenum, caecum, ventral midline, right dorsal colon). The biosensors measure acoustic signals and data were recorded in transport metric. Data were analysed using cross-classified multilevel random effects logistic regression including area under the receiver operator characteristic curve (AUC ROC). Sensitivity, specificity and accuracy were calculated for each modality., Results: All three modalities detected a reduction in gastrointestinal motility following xylazine administration with AUC ROC being 0.85, 0.84 and 0.86 for auscultation, ultrasonography and AGIS respectively. The sensitivity, specificity and accuracy for auscultation was 88, 71 and 75%; for ultrasonography was 67, 63 and 64%; and for AGIS was 69, 70 and 70%, respectively., Main Limitations: The study was performed in normal healthy horses and application of this device to clinical patients warrants further investigation., Conclusions: In this proof of principle study, AGIS was able to discriminate between horses given xylazine from those given 0.9% NaCl with comparable accuracy as auscultation and ultrasonography. The Summary is available in Spanish - see Supporting Information., (© 2018 EVJ Ltd.)

Associative learning theories regard the probability of reinforcement as the critical factor determining responding. However, the role of this factor in instrumental conditioning is not completely clear. In fact, free-operant experiments show that participants respond at a higher rate on variable ratio than on variable interval schedules even though the reinforcement probability is matched between the schedules. This difference has been attributed to the differential reinforcement of long inter-response times (IRTs) by interval schedules, which acts to slow responding. In the present study, we used a novel experimental design to investigate human responding under random ratio (RR) and regulated probability interval (RPI) schedules, a type of interval schedule that sets a reinforcement probability independently of the IRT duration. Participants responded on each type of schedule before a final choice test in which they distributed responding between two schedules similar to those experienced during training. Although response rates did not differ during training, the participants responded at a lower rate on the RPI schedule than on the matched RR schedule during the choice test. This preference cannot be attributed to a higher probability of reinforcement for long IRTs and questions the idea that similar associative processes underlie classical and instrumental conditioning.

Objective: To determine serum amyloid A (SAA) concentrations in the postoperative (PO) colic horse and its association with PO complications and infection., Study Design: Prospective case series., Animals: Fifty-one horses after colic surgery., Methods: Blood samples from horses undergoing exploratory celiotomy were analyzed for quantitative SAA and fibrinogen concentrations and for neutrophil count at days 0, 1, 2, and 4-6 and at hospital discharge., Results: Complications developed in 35 (69%) horses and included PO colic (n = 13, 25%), PO reflux (n = 11, 22%), intravenous catheter (IVC) complications (n = 11, 22%), low-grade fever (n = 11, 22%); surgical site infection (SSI; n = 9, 18%), high-grade fever (n = 7, 14%), and diarrhea (n = 4, 8%). There was an association between day 2 SAA and PO colic (P = .004), diarrhea (P = .042), IVC complications (P = .008), and PO reflux (P = .008) as well as day 4-6 SAA and PO colic (P = .004) and diarrhea (P = .018). Discharge SAA concentration was associated with SSI (P = .001). Fibrinogen concentrations at days 4-6 and at discharge were associated with PO colic (P = .003), diarrhea (P = .004), IVC complications (P = .002), and PO reflux (P = .023). No differences were seen in SAA, fibrinogen, or neutrophils between horses with PO infection vs those with non-infection-associated complications., Conclusion: Serum amyloid A was markedly increased in the PO period in all horses but did not differ between PO infection and noninfection complications. The amount of inflammation associated with PO colic and colic surgery was high and may have affected the predictive value of SAA for early PO infection., Clinical Significance: Although increases occurred earlier, measurement of SAA with a point-of-care analyzer may not be a more sensitive indicator of infection in the early PO colic horse than fibrinogen concentration. Serum amyloid A may help detect SSI in the late PO period., (© 2018 The American College of Veterinary Surgeons.)

Autobiographical accounts and a limited research literature suggest that adults with autism spectrum disorders can experience difficulties with decision-making. We examined whether some of the difficulties they describe correspond to quantifiable differences in decision-making when compared to adults in the general population. The participants (38 intellectually able adults with autism spectrum disorders and 40 neurotypical adults) were assessed on three tasks of decision-making (Iowa Gambling Task, Cambridge Gamble Task and Information Sampling Task), which quantified, respectively, decision-making performance and relative attention to negative and positive outcomes, speed and flexibility, and information sampling. As a caution, all analyses were repeated with a subset of participants ( n ASD  = 29 and n neurotypical  = 39) who were not taking antidepressant or anxiolytic medication. Compared to the neurotypical participants, participants with autism spectrum disorders demonstrated slower decision-making on the Cambridge Gamble Task, and superior performance on the Iowa Gambling Task. When those taking the medications were excluded, participants with autism spectrum disorders also sampled more information. There were no other differences between the groups. These processing tendencies may contribute to the difficulties self-reported in some contexts; however, the results also highlight strengths in autism spectrum disorders, such as a more logical approach to, and care in, decision-making. The findings lead to recommendations for how adults with autism spectrum disorders may be better supported with decision-making.

Illusory control refers to an effect in games of chance where features associated with skilful situations increase expectancies of success. Past work has operationalized illusory control in terms of subjective ratings or behaviour, with limited consideration of the relationship between these definitions, or the broader construct of agency. This study used a novel card-guessing task in 78 participants to investigate the relationship between subjective and behavioural illusory control. We compared trials in which participants (a) had no opportunity to exercise illusory control, (b) could exercise illusory control for free, or (c) could pay to exercise illusory control. Contingency Judgment and Intentional Binding tasks assessed explicit and implicit sense of agency, respectively. On the card-guessing task, confidence was higher when participants exerted control than in the baseline condition. In a complementary model, participants were more likely to exercise control when their confidence was high, and this effect was accentuated in the pay condition relative to the free condition. Decisions to pay were positively correlated with control ratings on the Contingency Judgment task, but were not significantly related to Intentional Binding. These results establish an association between subjective and behavioural illusory control and locate the construct within the cognitive literature on agency.

Physeal fractures are common musculoskeletal injuries in foals and should be included as a differential diagnosis for the lame or nonweightbearing foal. Careful evaluation of the patient, including precise radiographic assessment, is paramount in determining the options for treatment. Prognosis mostly depends on the patient's age, weight, and fracture location and configuration., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To evaluate short- and long-term outcome after medical and surgical management of horses with cecal impaction and to determine reasons for death or euthanasia., Study Design: Retrospective case series., Animals: Horses (n = 150)., Methods: Data collected from medical records (1991-2011) of horses with a diagnosis of cecal impaction, included signalment, history of recent disease/surgical procedure, admission data, management (medical, typhlotomy alone, jejunocolostomy), complications, and outcome. Short-term outcome (alive or dead at discharge) and long-term outcome (alive or dead at ≥1 year) were determined by telephone interview. Data were analyzed using a χ(2) or Fisher's exact test. Level of significance was P < .05., Results: Of 150 horses hospitalized with a diagnosis of cecal impaction, 102 (68%) had a history of recent disease or a surgical procedure. Thirty-eight horses (25%) had cecal perforation at admission and 3 horses (2%) were euthanatized without treatment. Of 109 horses treated, 59 (54%) were managed medically and 50 (46%) surgically (typhlotomy [26]; jejunocolostomy [24]). The proportion of horses alive at hospital discharge was significantly lower for horses managed medically (61%) compared with surgically (82%; P = .02) but there was no difference between horses managed with typhlotomy alone (77%) or with jejunocolostomy (88%; P = .47). There were 57% of horses managed medically alive at 1 year. There was a similar proportion of horses alive at 1 year after typhlotomy alone (73%) and jejunocolostomy (70%; P = .86)., Conclusions: Compared to the recent reports, the proportion of horses alive at hospital discharge was lower for both medically and surgically managed horses with cecal impaction. There was decreased survival for horses treated medically than those treated surgically; however, no significant difference was seen in survival between horses managed with typhlotomy alone versus jejunocolostomy., (© Copyright 2014 by The American College of Veterinary Surgeons.)

Adolescence is characterized by increases in both perceived stress and risk-taking, although the effects of stress on risk-sensitive decision-making have received little attention in adolescent groups. We report psychophysiological data from the healthy control group of a larger project examining neuroendocrine and neuropsychological function in boys with conduct disorder. The present analysis focussed on healthy male adolescents (n = 66) performing a decision-making task that involved selection between two wheel-of-fortune gambles. The task was completed in a neutral state, and again following a psychosocial stress induction that robustly increased salivary cortisol levels and baseline autonomic arousal. Task-related changes in electrodermal activity (EDA) and heart rate (HR) were monitored during the receipt of win and loss outcomes. On gamble choice, stress attenuated the difference in risk taking between the losses-only and wins-only trials (the 'reflection effect') and reduced risk-taking on one further gamble type (i.e. a stress × gamble type interaction). In the neutral condition, EDA and HR deceleration responses were significantly greater for losses compared to wins. This physiological differentiation of losses and wins was reduced under stress, with a significant attenuation of the HR deceleration response. In addition, higher trait impulsivity scores predicted reduced EDA differentiation of the outcomes, and reduced EDA stress reactivity. As a limitation, the order of neutral and stress sessions was not counter-balanced. Reduced psychophysiological discrimination between positive and negative outcomes may contribute to the effects of stress on risky decision-making in adolescents., (Copyright © 2013 Elsevier B.V. All rights reserved.)

We review evidence that supports the conclusion that people can and do learn in two distinct ways - one associative, the other propositional. No one disputes that we solve problems by testing hypotheses and inducing underlying rules, so the issue amounts to deciding whether there is evidence that we (and other animals) also rely on a simpler, associative system, that detects the frequency of occurrence of different events in our environment and the contingencies between them. There is neuroscientific evidence that associative learning occurs in at least some animals (e.g., Aplysia californica), so it must be the case that associative learning has evolved. Since both associative and propositional theories can in principle account for many instances of successful learning, the problem is then to show that there are at least some cases where the two classes of theory predict different outcomes. We offer a demonstration of cue competition effects in humans under incidental conditions as evidence against the argument that all such effects are based on cognitive inference. The latter supposition would imply that if the necessary information is unavailable to inference then no cue competition should occur. We then discuss the case of unblocking by reinforcer omission, where associative theory predicts an irrational solution to the problem, and consider the phenomenon of the Perruchet effect, in which conscious expectancy and conditioned response dissociate. Further discussion makes use of evidence that people will sometimes provide one solution to a problem when it is presented to them in summary form, and another when they are presented in rapid succession with trial-by trial information. We also demonstrate that people trained on a discrimination may show a peak shift (predicted by associative theory), but given the time and opportunity to detect the relationships between S+ and S-, show rule-based behavior instead. Finally, we conclude by presenting evidence that research on individual differences suggests that variation in intelligence and explicit problem solving ability are quite unrelated to variation in implicit (associative) learning, and briefly consider the computational implications of our argument, by asking how both associative and propositional processes can be accommodated within a single framework for cognition., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Delusions are the persistent and often bizarre beliefs that characterise psychosis. Previous studies have suggested that their emergence may be explained by disturbances in prediction error-dependent learning. Here we set up complementary studies in order to examine whether such a disturbance also modulates memory reconsolidation and hence explains their remarkable persistence. First, we quantified individual brain responses to prediction error in a causal learning task in 18 human subjects (8 female). Next, a placebo-controlled within-subjects study of the impact of ketamine was set up on the same individuals. We determined the influence of this NMDA receptor antagonist (previously shown to induce aberrant prediction error signal and lead to transient alterations in perception and belief) on the evolution of a fear memory over a 72 hour period: they initially underwent Pavlovian fear conditioning; 24 hours later, during ketamine or placebo administration, the conditioned stimulus (CS) was presented once, without reinforcement; memory strength was then tested again 24 hours later. Re-presentation of the CS under ketamine led to a stronger subsequent memory than under placebo. Moreover, the degree of strengthening correlated with individual vulnerability to ketamine's psychotogenic effects and with prediction error brain signal. This finding was partially replicated in an independent sample with an appetitive learning procedure (in 8 human subjects, 4 female). These results suggest a link between altered prediction error, memory strength and psychosis. They point to a core disruption that may explain not only the emergence of delusional beliefs but also their persistence.

Threat cues elicit defensive reactions mediated by limbic brain circuitry that is also implicated in risk-sensitive decision making. Building upon research looking at stress effects on decision making, a gambling task was administered to 65 healthy adults, comparing decision making on trials on which a red screen background signalled threat of shocks against trials when shocks could not occur. The threat cues elicited increased electrodermal activity and a sustained decrease in heart rate, consistent with defensive vigilance. The threat condition was associated with risk-avoidant choices, on trials where the risky option involved moderate losses and when choosing between options involving only losses. These effects were not explained by changes in latency. Threat exerts immediate effects on decision making and physiological arousal, biasing subjects towards safer alternatives, potentially through a magnified processing of loss information., (Copyright © 2012 Society for Psychophysiological Research.)

Near-miss outcomes during gambling are non-win outcomes that fall close to a pay-out. While objectively equivalent to an outright miss, near-misses motivate ongoing play and may therefore be implicated in the development of disordered gambling. Given naturalistic data showing increases in heart rate (HR) and electrodermal activity (EDA) during periods of real gambling play, we sought to explore the phasic impact of win, near-miss and full-miss outcomes on physiological arousal in a controlled laboratory environment. EDA and HR were monitored as healthy, student participants (n = 33) played a simulated slot-machine task involving unpredictable monetary wins. A second gambling distortion, perceived personal control, was manipulated within the same task by allowing the participant to select the play icon on some trials, and having the computer automatically select the play icon on other trials. Near-misses were rated as less pleasant than full-misses. However, on trials that involved personal choice, near-misses produced higher ratings of 'continue to play' than full-misses. Winning outcomes were associated with phasic EDA responses that did not vary with personal choice. Compared to full-misses, near-miss outcomes also elicited an EDA increase, which was greater on personal choice trials. Near-misses were also associated with greater HR acceleration than other outcomes. Near-miss outcomes are capable of eliciting phasic changes in physiological arousal consistent with a state of subjective excitement, despite their objective non-win status.

Objective: To identify history, clinical signs, endoscopic findings, treatment, and outcome of mature (> 8 years old) nonracehorses with epiglottic abnormalities., Design: Retrospective case series., Animals: 23 horses with an epiglottic abnormality., Procedures: Medical records of horses examined between 1990 and 2009 because of an epiglottic abnormality were reviewed to obtain information on signalment, history, clinical signs, clinical examination findings, upper airway endoscopic findings, diagnosis, surgical procedure, clinical management, postoperative care, and outcome., Results: Mean ± SD age was 16 ± 6 years (range, 9 to 30 years). Sixteen of the 23 (70%) horses had a primary complaint of a chronic cough. Thirteen (57%) horses had epiglottic entrapment, 7 (30%) had a subepiglottic granuloma, and 3 (13%) had a subepiglottic cyst. All 23 horses were treated surgically, with 1 (4%) requiring further surgical treatment. Follow-up examinations and conversations with owners indicated resolution of the primary complaint in 17 of the 23 (74%) horses, with 4 (24%) requiring prolonged medical treatment because of postoperative subepiglottic inflammation. Of the 6 horses without complete resolution, 4 (67%) had signs of recurrent airway obstruction and 2 (33%) developed persistent dorsal displacement of the soft palate following laryngotomy and subepiglottic membrane resection., Conclusions and Clinical Relevance: Results suggested that coughing is a common complaint in mature nonracehorses with epiglottic abnormalities. Therefore, upper airway endoscopy is recommended in the evaluation of older horses with a cough. Surgical treatment can be beneficial in most horses, with some requiring further postoperative medical treatment.

Regret and relief are complex emotional states associated with the counterfactual processing of nonobtained outcomes in a decision-making situation. In the "actor effect," a sense of agency and personal responsibility is thought to heighten these emotions. Using fMRI, we scanned volunteers (n = 22) as they played a task involving choices between two wheel-of-fortune gambles. We examined how neural responses to counterfactual outcomes were modulated by giving subjects the opportunity to change their minds, as a manipulation of personal responsibility. Satisfaction ratings to the outcomes were highly sensitive to the difference between the obtained and nonobtained outcome, and ratings following losses were lower on trials with the opportunity to change one's mind. Outcome-related activity in the striatum and orbitofrontal cortex was positively related to the satisfaction ratings. The striatal response was modulated by the agency manipulation: Following losses, the striatal signal was significantly lower when the subject had the opportunity to change his/her mind. These results support the involvement of frontostriatal mechanisms in counterfactual thinking and highlight the sensitivity of the striatum to the effects of personal responsibility.

We describe an original client-server approach to behavioral research control and the Whisker system, a specific implementation of this design. The server process controls several types of hardware, including digital input/output devices, multiple graphical monitors and touchscreens, keyboards, mice, and sound cards. It provides a way to access this hardware for client programs, communicating with them via a simple text-based network protocol based on the standard Internet protocol. Clients to implement behavioral tasks may be written in any network-capable programming language. Applications to date have been in experimental psychology and behavioral and cognitive neuroscience, using rodents, humans, nonhuman primates, dogs, pigs, and birds. This system is flexible and reliable, although there are potential disadvantages in terms of complexity. Its design, features, and performance are described.

According to dual-system accounts, instrumental learning is supported by both a goal-directed and a habitual system. Although behavioral control by the goal-directed system, through outcome-action associations, dominates with moderate training, stimulus-response associations are thought to form concurrently in the habit system. It is therefore challenging to isolate the neural substrate of the goal-directed system in neuroimaging research with healthy human volunteers. Recently, however, de Wit et al. (2007) developed an instrumental discrimination task that distinguishes between goal-directed and habit-based responding. In this task, cues are congruent, unrelated, or incongruent with subsequent outcomes. Whereas performance on congruent and control trials can be supported by both the goal-directed and habitual system, performance on the incongruent discrimination relies solely on the habit system. In the present study, we used this task with healthy participants undergoing functional magnetic resonance imaging to demonstrate that engagement of the goal-directed system during learning is reflected in increased activity in the ventromedial prefrontal cortex. Moreover, using a subsequent outcome devaluation manipulation, we show that this area is involved in guiding decision making when goal values change, even in the absence of external cues to guide performance. We can therefore exclude a purely Pavlovian account of ventromedial prefrontal function and unequivocally demonstrate its involvement in the acquisition as well as deployment of goal-directed knowledge.

Background: Although conduct disorder (CD) is associated with an increased susceptibility to substance use disorders, little is known about decision-making processes or reward mechanisms in CD. This study investigated decision making under varying motivational conditions in CD., Methods: Performances on the Risky Choice Task (RCT) and the Wisconsin Card Sorting Test (WCST) were assessed in 156 adolescents (84 control subjects, 34 with adolescence-onset CD, and 38 with early-onset CD). The RCT was performed twice, once under normal motivational conditions and once under conditions of increased motivation and psychosocial stress., Results: Increased motivation and stress led to more cautious decision making and changes in framing effects on the RCT in all groups, although such effects were least pronounced in the early-onset CD group. Participants from both CD subgroups selected the risky choice more frequently than control subjects. Under normal motivational conditions, early-onset CD participants chose the risky choice more frequently in trials occurring after small gains, relative to control subjects and adolescence-onset CD participants. Following adjustment for IQ differences, the groups did not differ significantly in terms of WCST performance., Conclusions: Differences in decision making between control subjects and individuals with CD suggest that the balance between sensitivity to reward and punishment is shifted in this disorder, particularly the early-onset form. Our data on modulation of decision making according to previous outcomes suggest altered reward mechanisms in early-onset CD. The WCST data suggest that impairments in global executive function do not underlie altered decision making in CD.

Rationale: Impulsivity is a cardinal feature of attention deficit hyperactivity disorder (ADHD), which is thought to underlie many of the cognitive and behavioural symptoms associated with the disorder. Impairments on some measures of impulsivity have been shown to be responsive to pharmacotherapy. However, impulsivity is a multi-factorial construct and the degree to which different forms of impulsivity contribute to impairments in ADHD or respond to pharmacological treatments remains unclear., Objectives: The aims of the study were to assess the effects of methylphenidate (MPH) on the performance of children with ADHD on measures of reflection-impulsivity and response inhibition and to compare with the performance of healthy volunteers., Methods: Twenty-one boys (aged 7-13 years) diagnosed with ADHD underwent a double-blind, placebo-controlled trial of MPH (0.5 mg/kg) during which they performed the Information Sampling Task (IST) and the Stop Signal Task. A healthy age- and education-matched control group was tested on the same measures without medication., Results: Children with ADHD were impaired on measures of response inhibition, but did not demonstrate reflection-impulsivity on the IST. However, despite sampling a similar amount of information as their peers, the ADHD group made more poor decisions. MPH improved performance on measures of response inhibition and variability of response, but did not affect measures of reflection-impulsivity or quality of decision-making., Conclusions: MPH differentially affected two forms of impulsivity in children with ADHD and failed to ameliorate their poor decision-making on the information sampling test.

The ventromedial prefrontal cortex (vmPFC) and insular cortex are implicated in distributed neural circuitry that supports emotional decision-making. Previous studies of patients with vmPFC lesions have focused primarily on decision-making under uncertainty, when outcome probabilities are ambiguous (e.g. the Iowa Gambling Task). It remains unclear whether vmPFC is also necessary for decision-making under risk, when outcome probabilities are explicit. It is not known whether the effect of insular damage is analogous to the effect of vmPFC damage, or whether these regions contribute differentially to choice behaviour. Four groups of participants were compared on the Cambridge Gamble Task, a well-characterized measure of risky decision-making where outcome probabilities are presented explicitly, thus minimizing additional learning and working memory demands. Patients with focal, stable lesions to the vmPFC (n = 20) and the insular cortex (n = 13) were compared against healthy subjects (n = 41) and a group of lesion controls (n = 12) with damage predominantly affecting the dorsal and lateral frontal cortex. The vmPFC and insular cortex patients showed selective and distinctive disruptions of betting behaviour. VmPFC damage was associated with increased betting regardless of the odds of winning, consistent with a role of vmPFC in biasing healthy individuals towards conservative options under risk. In contrast, patients with insular cortex lesions failed to adjust their bets by the odds of winning, consistent with a role of the insular cortex in signalling the probability of aversive outcomes. The insular group attained a lower point score on the task and experienced more 'bankruptcies'. There were no group differences in probability judgement. These data confirm the necessary role of the vmPFC and insular regions in decision-making under risk. Poor decision-making in clinical populations can arise via multiple routes, with functionally dissociable effects of vmPFC and insular cortex damage.

Dopamine replacement therapy (DRT) for Parkinson's disease (PD) has recently been linked to the development of a number of nonmotor behavioral control problems. Punding, one of these nonmotor problems, is a term used to describe complex, purposeless stereotyped behaviors such as the repetitive handling or sorting of objects. A self-report questionnaire was adapted to assess punding in the context of dysfunctional hobby-related activities. We report the results of a survey of PD outpatients from a PD research clinic (n = 141) and non-PD controls (n = 103); conducted to identify clinical and psychological factors predictive of punding behaviors. The PD group reported hobbies and activities, which scored significantly higher on the Punding Scale than controls. Higher impulsivity, poorer disease-related quality of life, younger age of disease onset, and concomitant daily medication dosage from dopamine receptor agonists were independently predictive of higher Punding Scale scores in the PD group. These findings are similar to those seen in dopamine dysregulation syndrome, and provide further evidence for the role of impulsivity and age at disease onset in DRT-related nonmotor behavioral problems in PD., (2007 Movement Disorder Society)

Delusions are maladaptive beliefs about the world. Based upon experimental evidence that prediction error-a mismatch between expectancy and outcome--drives belief formation, this study examined the possibility that delusions form because of disrupted prediction--error processing. We used fMRI to determine prediction-error-related brain responses in 12 healthy subjects and 12 individuals (7 males) with delusional beliefs. Frontal cortex responses in the patient group were suggestive of disrupted prediction-error processing. Furthermore, across subjects, the extent of disruption was significantly related to an individual's propensity to delusion formation. Our results support a neurobiological theory of delusion formation that implicates aberrant prediction-error signalling, disrupted attentional allocation and associative learning in the formation of delusional beliefs.

Buspirone is a serotonin 5-HT(1A) receptor agonist licensed for the treatment of anxiety. Other anxiolytic drugs such as benzodiazepines show significant sedative and other unwanted effects on cognition. Studies to date have yet to investigate cognitive effects of buspirone using well-validated computerized tests. The aim of this study was to assess acute subjective and cognitive effects of buspirone in healthy volunteers. Sixty healthy male volunteers received 20 mg buspirone, 30 mg buspirone, or placebo per os in a double-blind parallel groups design (N=20 per group). Subjective ratings (visual analogue scales) were completed at baseline, and at 1.5 and 3.5 hours post-capsule. Cognitive assessment was undertaken between 1.5 and 3.5 hours post-capsule, including tests of memory, executive planning, impulse control, decision making and cognitive flexibility. The 30 mg buspirone group showed significantly higher subjective ratings of contentedness 3.5 hours after capsule relative to placebo. Treatment and placebo groups did not differ significantly on cognitive measures. In contrast to benzodiazepines, the anxiolytic buspirone appears to lack detectable deleterious effects on cognition when administered acutely at clinically meaningful doses. Future research directions are discussed in relation to acute and chronic studies in neuropsychiatric populations.

The associative structure mediating goal-directed action was investigated using congruent and incongruent conditional discriminations. The stimulus was the same as the outcome in each component of the congruent discriminations, whereas the stimulus of one component of the incongruent discriminations was the same as the outcome of the other component. Humans, but not rats, learned the congruent discrimination more rapidly than the incongruent discrimination, a difference that the authors attribute to the fact that outcome-response associations caused response conflict in the incongruent discrimination. Moreover, responding was resistant to outcome devaluation following incongruent, but not congruent, training, suggesting that both humans and rats adopted a stimulus-response strategy to resolve the incongruent discrimination., ((c) 2007 APA, all rights reserved.)

Context: Establishing a neurobiological account of delusion formation that links cognitive processes, brain activity, and symptoms is important to furthering our understanding of psychosis., Objective: To explore a theoretical model of delusion formation that implicates prediction error-dependent associative learning processes in a pharmacological functional magnetic resonance imaging study using the psychotomimetic drug ketamine., Design: Within-subject, randomized, placebo-controlled study., Setting: Hospital-based clinical research facility, Addenbrooke's Hospital, Cambridge, England. The work was completed within the Wellcome Trust and Medical Research Council Behavioral and Clinical Neuroscience Institute, Cambridge., Participants: Fifteen healthy, right-handed volunteers (8 of whom were male) with a mean +/- SD age of 29 +/- 7 years and a mean +/- SD predicted full-scale IQ of 113 +/- 4 were recruited from within the local community by advertisement., Interventions: Subjects were given low-dose ketamine (100 ng/mL of plasma) or placebo while performing a causal associative learning task during functional magnetic resonance imaging. In a separate session outside the scanner, the dose was increased (to 200 ng/mL of plasma) and subjects underwent a structured clinical interview., Main Outcome Measures: Brain activation, blood plasma levels of ketamine, and scores from psychiatric ratings scales (Brief Psychiatric Ratings Scale, Present State Examination, and Clinician-Administered Dissociative States Scale)., Results: Low-dose ketamine perturbs error-dependent learning activity in the right frontal cortex (P = .03). High-dose ketamine produces perceptual aberrations (P = .01) and delusion-like beliefs (P = .007). Critically, subjects showing the highest degree of frontal activation with placebo show the greatest occurrence of drug-induced perceptual aberrations (P = .03) and ideas or delusions of reference (P = .04)., Conclusions: These findings relate aberrant prediction error-dependent associative learning to referential ideas and delusions via a perturbation of frontal cortical function. They are consistent with a model of delusion formation positing disruptions in error-dependent learning.

Synaesthesia, a neurological condition affecting approximately .05% of the population, is characterised by anomalous sensory perception: a stimulus in one sensory modality triggers an automatic, instantaneous, consistent response in another modality (e.g., sound evokes colour) or in a different aspect of the same modality (e.g., black text evokes colour). As evidence was limited to case studies based on self-report, the existence of synaesthesia was regarded with scepticism until the development of the Test of Genuineness (TOG) in 1987, which measures the consistency of stimulus-response linkage: synaesthetes typically score between 70-90% range, whereas controls typically score between 20-38%. However, the TOG had only limited ability to quantify the characteristics of visual synaesthesia. In this study, the revised Test of Genuineness (TOG-R), utilising the Pantone-based Cambridge Synaesthesia Charts, was given to 26 synaesthetes and 23 controls. Results confirmed that the TOG-R is equally accurate in the diagnosis of synaesthesia; synaesthetes scored significantly (t47 = 16.01, p < .001) higher (mean = 71.3%, SEM = 1.4%) than controls (mean = 33%, SEM = 2.0%). The TOG-R provides greater precision in quantifying the closeness of colour matches and enables a more detailed analysis of visual synaesthesia. Synaesthetes were phenotyped into broad- and narrowband based on their overall responsiveness to auditory stimuli, with bandwidth determined primarily by responsiveness to non-word stimuli. They were further sub-phenotyped based on responses to sub-groups of stimuli into word-colour (WC) and music-colour (MC). Development of this instrument has important implications for the diagnosis and phenotyping of visual synaesthesia.

Dickinson and Burke (1996) proposed a modified version of Wagner's (1981) SOP associative theory to explain retrospective revaluation of human causal judgments. In this modified SOP (MSOP), excitatory learning occurs when cue and outcome representations are either both directly activated or both associatively activated. By contrast, inhibitory learning occurs when one representation is directly activated while the other is associatively activated. Finite node simulations of MSOP yielded simple acquisition, overshadowing, blocking, and inhibitory learning under forward contingencies. Importantly, retrospective revaluation was predicted in the form of unovershadowing and backward inhibitory learning. However, MSOP did not yield backward blocking. These predictions are evaluated against the relevant empirical evidence and contrasted with the predictions of other associative theories that have been applied to retrospective revaluation of human causal and predictive learning.

Background: Cognitive performance was compared in the genetically and neurobiologically related disorders of Tourette's syndrome (TS) and obsessive-compulsive disorder (OCD), in three domains of executive function: planning, decision-making and inhibitory response control., Method: Twenty TS patients, twenty OCD patients and a group of age- and IQ-matched normal controls completed psychometric and computerized cognitive tests and psychiatric rating scales. The cognitive tests were well-characterized in terms of their sensitivity to other fronto-striatal disorders, and included pattern and spatial recognition memory, attentional set-shifting, and a Go/No-go set-shifting task, planning, and decision-making., Results: Compared to controls, OCD patients showed selective deficits in pattern recognition memory and slower responding in both pattern and spatial recognition, impaired extra-dimensional shifting on the set-shifting test and impaired reversal of response set on the Go/No-go test. In contrast, TS patients were impaired in spatial recognition memory, extra-dimensional set-shifting, and decision-making. Neither group was impaired in planning. Direct comparisons between the TS and OCD groups revealed significantly different greater deficits for recognition memory latency and Go/No-go reversal for the OCD group, and quality of decision-making for the TS group., Conclusions: TS and OCD show both differences (recognition memory, decision-making) and similarities (set-shifting) in selective profiles of cognitive function. Specific set-shifting deficits in the OCD group contrasted with their intact performance on other tests of executive function, such as planning and decision-making, and suggested only limited involvement of frontal lobe dysfunction, possibly consistent with OCD symptomatology.

Associative learning theory assumes that prediction error is a driving force in learning. A competing view, probabilistic contrast (PC) theory, is that learning and prediction error are unrelated. We tested a learning phenomenon that has proved troublesome for associative theory--retrospective revaluation--to evaluate these two models. We previously showed that activation in right lateral prefrontal cortex (PFC) provides a reliable signature for the presence of prediction error. Thus, if the associative view is correct, retrospective revaluation should be accompanied by right lateral PFC activation. PC theory would be supported by the absence of this activation. Right PFC and ventral striatal activation occurred during retrospective revaluation, supporting the associative account. Activations appeared to reflect the degree of revaluation, predicting later brain responses to revalued cues. Our results support a modified associative account of retrospective revaluation and demonstrate the potential of functional neuroimaging as a tool for evaluating competing learning models.

Prediction error--a mismatch between expected and actual outcome--is critical to associative accounts of inferential learning. However, it has proven difficult to explore the effects of prediction error using functional magnetic resonance imaging (fMRI) while excluding the confounding effects of stimulus novelty and incorrect responses. In this event-related fMRI study we used a three-stage experiment generating preventative- and super-learning conditions. In both cases, it was possible to generate prediction error within a causal associative learning experiment while subtracting the effects of novelty and error. We show that right lateral prefrontal cortex (PFC) activation is sensitive to the magnitude of prediction error. Furthermore, super-learning activation in this region of PFC correlates, across subjects, with the amount learned. We thus provide direct evidence for a brain correlate of the surprise-dependent mechanisms proposed by associative accounts of causal learning. We show that activity in right lateral PFC is sensitive to the magnitude, though not the direction, of the prediction error. Furthermore, its activity is not directly explicable in terms of novelty or response errors and appears directly related to the learning that arises out of prediction error.

Rationale: Diazepam has well known amnestic and sedative effects but effects on fronto-executive function remain largely uninvestigated, especially on neuropsychologically validated tests of risk taking and orbitofrontal cortex function., Objectives: We aimed to determine the impact of diazepam on a variety of executive tasks., Methods: The effects of 5, 10 and 20 mg of diazepam on a battery of neuropsychological tests were investigated using a randomised, double blind, placebo-controlled design. Seventy-five adult men were recruited. The Rogers et al. (1999b) test of risk-taking was given along with tasks from the CANTAB battery., Results: Diazepam impaired performance on the Tower of London test of planning, without influencing visual pattern recognition memory. Subjects who had taken diazepam made more risky choices on the risk-taking task. On two speeded reaction time tasks diazepam impaired discrimination sensitivity and increased the bias to respond., Conclusions: In contrast to the well-known sedative effects of diazepam, we demonstrate disinhibitory effects on two speeded reaction time tasks. Our results show that diazepam can impair performance on reaction time tasks both by impairing sensitivity and by increasing the bias to respond. Furthermore diazepam impaired performance on tests of planning and risky decision making that depend predominantly on dorsolateral and orbitofrontal regions of the prefrontal cortex, respectively.

The dopamine D2 receptor antagonist sulpiride can produce a range of cognitive deficits in normal volunteers, consistent with those seen in Parkinson's disease (PD). This, together with studies in experimental animals, implies sulpiride might be acting in the striatum. However, subtle changes in prefrontal cortex (PFC) activity are seen following L-Dopa withdrawal in PD during working memory tasks, suggesting that this may be a further site of action for dopamine D2 receptor antagonists. We have investigated the effects of sulpiride within the PFC and striatum in normal male volunteers. In two separate experiments, using identical PET regional cerebral blood flow (rCBF) methods, a combined drug and psychological challenge was performed, utilising working memory and planning tasks, and oral sulpiride 400 mg and placebo. Data were analysed using SPM99. Sulpiride increased striatal rCBF bilaterally and the working memory and planning tasks activated discrete frontoparietal networks in keeping with previous studies. However, for the working memory tasks, no changes in performance or task-induced rCBF were observed after sulpiride. For the planning task, improved performance was seen on sulpiride. Also, sulpiride attenuated striatal activity during planning (as assessed using a small volume correction, P<0.05 corrected), and this attenuation was related to performance changes. These findings suggest that (1) sulpiride produces clear increases in striatal rCBF, (2) in contrast to previous studies no effects of sulpiride on performance of the working memory tasks or the associated neural networks were observed, and (3) sulpiride may modulate performance of more complex cognitive tasks via alterations in striatal neural activity.

We investigated blocking and retrospective revaluation of causal judgements using a scenario in which food cues acted as potential causes of an allergic reaction as the outcome. In the blocking contingency, the treatment cues were either paired or unpaired with the outcome prior to a second stage in which sequential compounds of treatment and target cues were paired with the outcome. The order of this compound and treatment training was reversed in retrospective revaluation contingencies. When the interstimulus interval between the treatment and target cues was unfilled on compound trials (Experiments 1 and 3), both blocking and retrospective revaluation were observed in that the target cue trained in compound with the paired treatment cue attracted lower causal ratings than the target cue trained in compound with the unpaired treatment cue. By contrast, performing a mental arithmetic task using numerals presented during the interstimulus interval had no effect on the magnitude of blocking but rendered retrospective revaluation unreliable (Experiments 2 and 3). These results provide further support for accounts of revaluation based upon within-compound associations.

In three experiments, participants learned which of a variety of foods were capable of causing an allergic reaction in a hypothetical patient during training in which a compound of a treatment and a target food cue was paired with the reaction. In Experiment 1 the causal ratings of the target cue were increased if the treatment cue was pretrained as a preventative cause of the reaction. Experiments 2 and 3 demonstrated that the magnitude of this super-learning is unaffected by the order of compound and treatment cue training. The final study also showed that forward super-learning is not induced solely by simple exposure to the treatment cue prior to compound training but, rather, depends upon training the treatment cue as a preventative cause, whereas retrospective super-learning may be due merely to exposure of the treatment cue. These results are problematic for contingency-based accounts of causal induction but accord with modified and extended associative theories.