Prefrontal cortex lesions disrupt the contextual control of response conflict

The prefrontal cortex has been implicated in multiple forms of goal-directed behavior. Rats with pretraining lesions to the prefrontal cortex (PFC) or specific lesions to the anterior cingulate cortex (ACC) were trained and tested on a novel behavioral procedure measuring aspects of cue and response competition typical of tests of prefrontal function in humans. Rats were trained on two biconditional discrimination tasks, one auditory and one visual, in two discriminably different contexts. At test, they received presentations of audiovisual compounds of these training stimuli in both contexts, in extinction. These compounds were formed in such way that the individual elements had dictated either the same (congruent trials) or different (incongruent trials) responses during training. Sham-operated rats used the contextual cues to disambiguate the conflicting response information provided by incongruent stimulus compounds. ACC lesions impaired the contextual control of instrumental responding during incongruent cues during only the initial period of cue presentation, whereas larger PFC lesions abolished incongruent cue performance completely. Neither biconditional discrimination acquisition, nor test performance during congruent stimulus compounds, were affected by the lesions. These findings are consistent with human and nonhuman primate studies, indicating a role for the PFC in the processes by which cues come to control behavior in the face of conflicting information and the ACC specifically in processes such as detection of response conflict. This procedure provides a good foundation for an improved understanding of the disruption to goal-directed behavior seen with frontal dysfunction in a number of neuropsychological disorders including schizophrenia

Healthcare Access and Quality Index based on mortality from causes amenable to personal health care in 195 countries and territories, 1990-2015 : a novel analysis from the Global Burden of Disease Study 2015

Background National levels of personal health-care access and quality can be approximated by measuring mortality rates from causes that should not be fatal in the presence of effective medical care (ie, amenable mortality). Previous analyses of mortality amenable to health care only focused on high-income countries and faced several methodological challenges. In the present analysis, we use the highly standardised cause of death and risk factor estimates generated through the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to improve and expand the quantification of personal health-care access and quality for 195 countries and territories from 1990 to 2015. Methods We mapped the most widely used list of causes amenable to personal health care developed by Nolte and McKee to 32 GBD causes. We accounted for variations in cause of death certification and misclassifications through the extensive data standardisation processes and redistribution algorithms developed for GBD. To isolate the effects of personal health-care access and quality, we risk-standardised cause-specific mortality rates for each geography-year by removing the joint effects of local environmental and behavioural risks, and adding back the global levels of risk exposure as estimated for GBD 2015. We employed principal component analysis to create a single, interpretable summary measure-the Healthcare Quality and Access (HAQ) Index-on a scale of 0 to 100. The HAQ Index showed strong convergence validity as compared with other health-system indicators, including health expenditure per capita (r= 0.88), an index of 11 universal health coverage interventions (r= 0.83), and human resources for health per 1000 (r= 0.77). We used free disposal hull analysis with bootstrapping to produce a frontier based on the relationship between the HAQ Index and the Socio-demographic Index (SDI), a measure of overall development consisting of income per capita, average years of education, and total fertility rates. This frontier allowed us to better quantify the maximum levels of personal health-care access and quality achieved across the development spectrum, and pinpoint geographies where gaps between observed and potential levels have narrowed or widened over time. Findings Between 1990 and 2015, nearly all countries and territories saw their HAQ Index values improve; nonetheless, the difference between the highest and lowest observed HAQ Index was larger in 2015 than in 1990, ranging from 28.6 to 94.6. Of 195 geographies, 167 had statistically significant increases in HAQ Index levels since 1990, with South Korea, Turkey, Peru, China, and the Maldives recording among the largest gains by 2015. Performance on the HAQ Index and individual causes showed distinct patterns by region and level of development, yet substantial heterogeneities emerged for several causes, including cancers in highest-SDI countries; chronic kidney disease, diabetes, diarrhoeal diseases, and lower respiratory infections among middle-SDI countries; and measles and tetanus among lowest-SDI countries. While the global HAQ Index average rose from 40.7 (95% uncertainty interval, 39.0-42.8) in 1990 to 53.7 (52.2-55.4) in 2015, far less progress occurred in narrowing the gap between observed HAQ Index values and maximum levels achieved; at the global level, the difference between the observed and frontier HAQ Index only decreased from 21.2 in 1990 to 20.1 in 2015. If every country and territory had achieved the highest observed HAQ Index by their corresponding level of SDI, the global average would have been 73.8 in 2015. Several countries, particularly in eastern and western sub-Saharan Africa, reached HAQ Index values similar to or beyond their development levels, whereas others, namely in southern sub-Saharan Africa, the Middle East, and south Asia, lagged behind what geographies of similar development attained between 1990 and 2015. Interpretation This novel extension of the GBD Study shows the untapped potential for personal health-care access and quality improvement across the development spectrum. Amid substantive advances in personal health care at the national level, heterogeneous patterns for individual causes in given countries or territories suggest that few places have consistently achieved optimal health-care access and quality across health-system functions and therapeutic areas. This is especially evident in middle-SDI countries, many of which have recently undergone or are currently experiencing epidemiological transitions. The HAQ Index, if paired with other measures of health-systemcharacteristics such as intervention coverage, could provide a robust avenue for tracking progress on universal health coverage and identifying local priorities for strengthening personal health-care quality and access throughout the world. Copyright (C) The Author(s). Published by Elsevier Ltd.Peer reviewe

Both motivational and training factors affect response conflict choice performance in rats

Rats were trained on two biconditional discrimination tasks, in two different contexts, and were rewarded with two different outcomes. At test, they received presentations of audiovisual compounds of these training stimuli, in extinction. These compounds were formed in such way that the individual elements had dictated either the same (congruent trials) or different (incongruent trials) responses during training, and each stimulus element had previously been rewarded with a different outcome. Previous research has shown that rats use the contextual cues to disambiguate the conflicting response information provided by incongruent stimulus compounds. Experiment 1 demonstrated that this contextual control was goal-directed in the sense that it depended on the current value of the outcome and Experiment 2 demonstrated that both the training history of the biconditional stimuli and motivational influences influenced the contextual control of responding on incongruent trials. These results are discussed in relation to current models of choice behaviour

Contextual Control of Choice Performance: Behavioral, Neurobiological, and Neurochemical Influences

An important aspect of decision making is the ability of responses to be controlled by different cues in different situations or contexts, especially when there is conflict between alternative responses or actions.Recently, a context-dependent biconditional task has been developed for rats that mimic some aspects of response conflict seen in human cognitive paradigms, such as the Stroop task. In this task, contextual cues are used to disambiguate conflicting response information provided by audiovisual compound stimuli. Here we review current findings that investigate some of the behavioral, neurobiological, and neurochemical mechanisms that underlie this use of contextual or task-setting information to resolve response conflict, and discuss future ways in which this research can be extended

Inactivation of the infralimbic prefrontal cortex in rats reduces the influence of inappropriate habitual responding in a response-conflict task

Previous research suggests the infralimbic cortex is important in situations when there is competition between goal-directed and habitual responding. Here we used a response conflict procedure to further explore the involvement of the infralimbic cortex in this relationship. Rats received training on two instrumental biconditional discriminations, one auditory and one visual, in two distinct contexts. One discrimination was “over-trained” relative to the other, “under-trained,” discrimination in the ratio 3:1. At test, animals were presented with incongruent audiovisual stimulus compounds of the training stimuli in the under-trained context. The stimulus elements of these test compounds have previously dictated different lever press responses during training. Rats receiving control infusions into the infralimbic cortex showed a significant interference effect, producing more responses to the over-trained (habitual), but context-inappropriate, stimulus element of the incongruent compound. This interference effect was abolished by inactivation of the infralimbic cortex; animals showed a reduced tendency to produce the habitual but inappropriate response compared with animals receiving control infusions. This finding provides evidence that the infralimbic cortex is involved in attenuating the influence of goal-directed behavior, for example context-appropriate responding

Contextual control of biconditional task performance: Evidence for cue and response competition in rats

A novel paradigm is presented that was designed to mimic aspects of cue and response competition seen in humans in conflict procedures such as the Stroop task. Rats were trained simultaneously on two biconditional discrimination tasks, one auditory and one visual, in two different contexts: C1, in which A1:LP1 → R, A2:LP2 → R; and C2, in which V1:LP1 → R, V2:LP2 → R, where C1/C2 represent different training contexts (produced by different operant chambers), A1/A2 are different auditory cues, V1/V2 are different visual cues, LP1/LP2 are discrete operant responses, and R is reward. At test, rats received presentations of audiovisual compounds of these training stimuli in extinction. These compounds had dictated either the same (A1V1 or A2V2) or different (A1V2 or A2V1) responses during training: termed congruent and incongruent trials, respectively. Experiment 1 showed that following equal training on the two biconditional tasks, the contextual cues came to control responding to conflicting information provided by incongruent stimulus compounds such that animals responded according to the stimulus element previously trained in that test context. Experiment 2 demonstrated that differential training on the biconditional discriminations (with rats receiving training on the two discriminations in the ratio 31) resulted in greater interference from the overtrained task when animals were tested in the undertrained context. This finding is similar to the classic Stroop asymmetry seen in human performance whereby dominant word reading interferes with colour naming for incongruent colour–word compounds. Further analysis also revealed some evidence for a reverse Stroop effect in which the undertrained stimulus element interfered with performance on the overtrained task

Inactivation of the prelimbic, but not infralimbic, prefrontal cortex impairs the contextual control of response conflict in rats

One fundamental function of the prefrontal cortex (PFC) is to guide context-appropriate behaviour in situations of response conflict. Haddon and Killcross recently developed a task in rats which mimics some aspects of response conflict seen in human cognitive paradigms such as the Stroop task. Using this paradigm they demonstrated that large PFC lesions including the prelimbic (PL), infralimbic (IL) and anterior cingulate cortices (ACC) selectively impaired performance on incongruent trials which required the use of task-setting contextual cues to control responding in the face of ambiguous response information. The current experiment was conducted to determine whether specific PFC regions were responsible for the deficit in incongruent performance. Rats were trained on two instrumental biconditional discriminations, one auditory and one visual, in two different contexts. Following acquisition, rats were implanted with guide cannulae aimed at the PL or the IL cortices of the rat prefrontal cortex. Following retraining, rats received microinfusions of the GABAA agonist muscimol or artificial cerebrospinal fluid (aCSF) into either the PL or the IL prior to presentations of novel congruent and incongruent audiovisual compounds of the training stimuli in extinction. Results showed that temporary inactivation of the PL cortex led to a selective deficit on incongruent compound trials, but left congruent, and hence biconditional task performance intact. By contrast, IL inactivation had no effect on the accuracy of responding during either congruent or incongruent trials. These results suggest that the PL cortex is necessary for the use of task-setting contextual cues to control responding to conflicting information