Attentional effects of lesions to the anterior cingulate cortex: How prior reinforcement influences distractibility.

Morphological changes in the anterior cingulate cortex are found in subjects with schizophrenia, attention deficit hyperactivity disorder, and obsessive–compulsive disorder. These changes are hypothesized to underlie the impairments these individuals show on tasks that require cognitive control. The anterior cingulate cortex has previously been shown to be active in situations involving high conflict, presentation of salient, distracting stimuli, and error processing, that is, situations that occur when a shift in attention or responding is required. However, there is some uncertainty as to what specific role the anterior cingulate cortex plays in these situations. The current study used converging evidence from two behavioral paradigms to determine the effects of excitotoxic lesions in the anterior cingulate cortex on executive control. The first assay tests reversal learning, attentional set formation and shifting. The second assesses sustained attention with and without distractors. Animals with anterior cingulate cortex lesions were impaired during reinforcement reversals, discriminations that required subjects to disregard previously relevant stimulus attributes and showed a more rapid decline in attentional ability than Sham-Lesioned subjects when maintaining sustained attention for extended periods of time. These results are consistent with the hypothesis that the anterior cingulate cortex is involved in attending to stimulus attributes that currently predict reinforcement in the presence of previously relevant, salient distractors and maintaining sustained attention over prolonged time on task. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Anterior cingulate activity and level of cognitive conflict: Explicit comparisons.

The role of anterior cingulate cortex (ACC) in attention is a matter of debate. One hypothesis suggests that its role is to monitor response-level conflict, but explicit evidence is somewhat lacking. In this study, the activation of ACC was compared in (a) color and number standard Stroop tasks in which response preparation and interference shared modality (response-level conflict) and (b) color and number matching Stroop tasks in which response preparation and interference did not share modality (non-response-level conflict). In the congruent conditions, there was no effect of task type. In the interference conditions, anterior cingulate activity in the matching tasks was less than that in the standard tasks. These results support the hypothesis that ACC specifically mediates generalized modality-independent selection processes invoked by response competition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Right anterior cingulate: A neuroanatomical correlate of aggression and defiance in boys.

Variation in emotional processes may contribute to aggressive and defiant behavior. This study assessed these problem behaviors in a large sample of children and adolescents in relation to the volume of two cortical regions with prominent roles in emotion processing, the anterior cingulate cortex (ACC) and ventromedial prefrontal cortex (vmPFC). One hundred seventeen participants (61 boys, 56 girls), ages 7-17, were recruited from the community. Aggressive and defiant behavior was measured using the parent- and teacher-reported Pediatric Behavior Scale and volumetric measures were generated using structural MRI. Regression analyses indicated a significant sex X ACC volume interaction in predicting aggressive and defiant behavior, without significant results for the vmPFC. Follow-up analyses showed that aggressive and defiant behavior is associated with decreased right ACC volume in boys and a nonsignificant reduction in left ACC volume in girls. These results are consistent with the notion that the right ACC acts as a neuroanatomical correlate of aggression and defiance in boys. The authors discuss this finding in light of its implications for understanding the neural correlates of antisocial behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Strain difference in the effect of infralimbic cortex lesions on fear extinction in rats.

The infralimbic division of the medial prefrontal cortex (IL) has been implicated in the consolidation and retention of extinction memories. However, the effects of IL lesions on the retention of extinction memory are inconsistent. In the present experiments, we examined whether rat strain influences the effects of IL lesions on extinction. In Experiment 1, Sprague-Dawley (SD) or Long-Evans (LE) rats received a standard auditory fear conditioning procedure, which was followed by an extinction session; freezing served as the index of conditional fear. Our results reveal that focal IL lesions impair the retention of extinction in SD, but not LE rats. In addition to the strain difference in sensitivity to IL lesions, LE rats exhibited significantly higher levels of contextual fear before the outset of extinction training than SD rats. In a second experiment we thus examined whether contextual fear influenced the sensitivity of extinction to IL lesions in LE rats. LE rats received the same conditioning as in Experiment 1, and then were either merely exposed to a novel context or administered unsignaled shocks in that context, followed by extinction and test sessions. Our results reveal that LE rats with IL lesions showed normal extinction regardless of the levels of contextual fear manifest before extinction. Thus, we conclude that rat strain is an important variable that influences the role of infralimbic cortex in fear extinction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Involvement of the rat medial prefrontal cortex in novelty detection.

The prefrontal cortex in humans has been implicated in processes that underlie novelty detection and attention. This study examined the contribution of the rat medial prefrontal cortex to novelty detection using the targeting, or orienting, response (OR) as a behavioral index. Lesions to the medial prefrontal cortex (specifically the prelimbic and infralimbic cortices) influenced neither the OR to a novel visual stimulus from a localized light source (V1), nor the change in this OR over the course of a series of exposures to V1. However, after exposure to V1, the OR to a 2nd visual stimulus from the same source, V2, was more pronounced in control rats than in lesioned rats. These results suggest that the medial prefrontal cortex in the rat contributes to the process of novelty detection. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of temporary inactivation of the orbital cortex in the signal attenuation rat model of obsessive compulsive disorder.

Rats undergoing extinction of lever pressing after an external feedback for this behavior was attenuated by extinguishing its Pavlovian association with the reward (signal attenuation) exhibit compulsive lever pressing. The present study tested the effects of temporary inactivation of the orbital cortex in rats undergoing extinction of lever pressing that was or was not preceded by signal attenuation (post-training signal attenuation and regular extinction, respectively). Orbital inactivation led to a nonspecific decrease in lever pressing in rats undergoing post-training signal attenuation and to the emergence of compulsive-like behavior in rats undergoing regular extinction. These results suggest that orbital inactivation and extinguishing a Pavlovian stimulus-reinforcer contingency have a similar effect on lever pressing and are in line with previous findings implicating the orbital cortex in mediating the effects of previously acquired stimulus-reinforcer associations on operant behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The costs of supervised classification: The effect of learning task on conceptual flexibility.

Research has shown that learning a concept via standard supervised classification leads to a focus on diagnostic features, whereas learning by inferring missing features promotes the acquisition of within-category information. Accordingly, we predicted that classification learning would produce a deficit in people's ability to draw novel contrasts—distinctions that were not part of training—compared with feature inference learning. Two experiments confirmed that classification learners were at a disadvantage at making novel distinctions. Eye movement data indicated that this conceptual inflexibility was due to (a) a narrower attention profile that reduces the encoding of many category features and (b) learned inattention that inhibits the reallocation of attention to newly relevant information. Implications of these costs of supervised classification learning for views of conceptual structure are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A preliminary investigation of cognitive flexibility for emotional information in major depressive disorder and non-psychiatric controls.

Clinical research suggests that individuals with major depressive disorder (MDD) are cognitively inflexible, exhibiting ruminative, rigid, and automatic thoughts within a negative schema. However, existing neuropsychological research on cognitive flexibility in this population has not employed emotional stimuli. Because research suggests that the performance of individuals with MDD is modulated when emotional stimuli are used, this study investigates the impact of emotional stimuli on cognitive flexibility performance through a novel emotional modification of the Wisconsin Card Sorting Test. Controls were less flexible when stimuli were positive and individuals with MDD were less flexible when stimuli were negative relative to the controls. These divergent styles of responding to emotional information may contribute to the relative risk or protection from depressed mood. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The cognitive and neural architecture of sequence representation.

The authors theorize that 2 neurocognitive sequence-learning systems can be distinguished in serial reaction time experiments, one dorsal (parietal and supplementary motor cortex) and the other ventral (temporal and lateral prefrontal cortex). Dorsal system learning is implicit and associates noncategorized stimuli within dimensional modules. Ventral system learning can be implicit or explicit. It also allows associating events across dimensions and therefore is the basis of cross-task integration or interference, depending on degree of cross-task correlation of signals. Accordingly, lack of correlation rather than limited capacity is responsible for dual-task effects on learning. The theory is relevant to issues of attentional effects on learning; the representational basis of complex, sequential skills; hippocampal- versus basal ganglia-based learning; procedural versus declarative memory; and implicit versus explicit memory. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Enhanced facilitation of spatial attention in schizophrenia.

Objective: While attentional functions are usually found to be impaired in schizophrenia, a review of the literature on the orienting of spatial attention in schizophrenia suggested that voluntary attentional orienting in response to a valid cue might be paradoxically enhanced. We tested this hypothesis with orienting tasks involving the cued detection of a laterally presented target stimulus. Method: Subjects were chronic schizophrenia patients (SZ) and matched healthy control subjects (HC). In Experiment 1 (15 SZ, 16 HC), cues were endogenous (arrows) and could be valid (100% predictive) or neutral with respect to the subsequent target position. In Experiment 2 (16 SZ, 16 HC), subjects performed a standard orienting task with unpredictive exogenous cues (brightening of the target boxes). Results: In Experiment 1, SZ showed a larger attentional facilitation effect on reaction time than HC. In Experiment 2, no clear sign of enhanced attentional facilitation was found in SZ. Conclusions: The voluntary, facilitatory shifting of spatial attention may be relatively enhanced in individuals with schizophrenia in comparison to healthy individuals. This effect bears resemblance to other relative enhancements of information processing in schizophrenia such as saccade speed and semantic priming. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Systemic and Prefrontal Cortical NMDA Receptor Blockade Differentially Affect Discrimination Learning and Set-Shift Ability in Rats.

The authors examined discrimination rule learning and extradimensional set-shifting ability in rats given systemic or intracranial injections of the N-methyl-D-aspartate (NMDA) receptor antagonist MK801. Pretraining systemic injections of MK801 impaired both the acquisition of the initial discrimination rule (Set 1) and the shift to the 2nd rule (Set 2). Pretraining intramedial prefrontal cortical (mPFC) administration of MK801 did not impair Set 1 acquisition. Intra-mPFC injection of MK801 was previously found to impair Set 2 acquisition. Impaired Set 2 performance was due to increased cognitive perseveration. The data suggest that discrimination learning in naive subjects requires NMDA receptors outside the mPFC, whereas NMDA receptors within the mPFC are selectively involved in the modification of previous knowledge and/or the inhibition of previously learned responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Involvement of catecholamine neurotransmission in the rat anterior cingulate in effort-related decision making.

This study examined whether catecholamine-mediated signals in the anterior cingulate cortex (ACC) contribute to effort-based decision making. Rats were tested after 6-hydroxydopamine or vehicle infusions into the ACC in a T maze cost-benefit task in which the rats could choose either to climb a barrier to obtain a high reward in one arm or run into the other arm without a barrier to obtain a low reward. Results demonstrate that infusions of 6-hydroxydopamine induced a near total loss of tyrosine hydroxylase-positive fibers in the ACC. Unlike sham-lesioned rats, 6-hydroxydopamine-lesioned rats exhibited a reduced preference for the high-cost-high-reward response option when given the choice of obtaining a low reward with little effort. Thus, catecholamine-mediated signals in the ACC could play a role in effort-based decision making. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selective lesions of the nucleus basalis magnocellularis impair cognitive flexibility.

The authors tested the hypothesis that the cholinergic nucleus basalis magnocellularis (NBM) is involved in solving problems requiring cognitive flexibility. Rats with 192 IgG-saporin lesions of the NBM were assessed for perseveration (i.e., cognitive inflexibility) in the serial reversal of an operant discrimination and during subsequent extinction testing. It was hypothesized that the NBM lesion and control groups would not differ in the acquisition of the initial, simple discrimination, because this task does not demand cognitive flexibility. In contrast, it was hypothesized that the NBM lesion group would show perseveration during serial reversal and extinction testing. Results generally supported these hypotheses, suggesting that the NBM plays an important role in mediating cognitive flexibility. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A meta-analysis of the effect of cognitive bias modification on anxiety and depression.

Cognitive biases have been theorized to play a critical role in the onset and maintenance of anxiety and depression. Cognitive bias modification (CBM), an experimental paradigm that uses training to induce maladaptive or adaptive cognitive biases, was developed to test these causal models. Although CBM has generated considerable interest in the past decade, both as an experimental paradigm and as a form of treatment, there have been no quantitative reviews of the effect of CBM on anxiety and depression. This meta-analysis of 45 studies (2,591 participants) assessed the effect of CBM on cognitive biases and on anxiety and depression. CBM had a medium effect on biases (g = 0.49) that was stronger for interpretation (g = 0.81) than for attention (g = 0.29) biases. CBM further had a small effect on anxiety and depression (g = 0.13), although this effect was reliable only when symptoms were assessed after participants experienced a stressor (g = 0.23). When anxiety and depression were examined separately, CBM significantly modified anxiety but not depression. There was a nonsignificant trend toward a larger effect for studies including multiple training sessions. These findings are broadly consistent with cognitive theories of anxiety and depression that propose an interactive effect of cognitive biases and stressors on these symptoms. However, the small effect sizes observed here suggest that this effect may be more modest than previously believed. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

The spatial focus of attention is controlled at perceptual and cognitive levels.

Selective attention has been hypothesized to reduce distractor interference at both perceptual and postperceptual levels (Lavie, 2005), respectively, by focusing perceptual resources on the attended location and by blocking at postperceptual levels distractors that survive perceptual selection. This study measured the impact of load on these selection mechanisms using a flanker paradigm (Eriksen & St. James, 1986) and indexing distractor interference as a function of separation. It distinguished changes in the extent of focus of the distractor-interference function of separation (reflecting perceptual selection) from changes in the amplitude of distractor interference not accompanied by changes in focus (reflecting postperceptual selection). It showed that: (1) the spatial profile of perceptual resources is shaped like a “Mexican hat” (Müller et al., 2005); (2) increasing perceptual load focuses perceptual resources (Caparos & Linnell, 2009); (3) increasing cognitive load defocuses perceptual resources; and (4) participants with reduced working-memory span show reduced postperceptual blocking of distractors. While these findings are consistent with two levels of selective attention, they show that the first perceptual level is affected not only by perceptual but also by cognitive-control mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Double dissociation and hierarchical organization of strategy switches and reversals in the rat PFC.

Prelimbic–infralimbic cortex (PL-IL) and orbitofrontal cortex (OFC) influence behavioral flexibility in the rat. The authors tested the effects of PL-IL or OFC infusion with the GABA agonist muscimol in the context of 2 flexible responding tasks: strategy switching and reversal. Muscimol infusion into PL-IL impaired retention of strategy switches but not reversals, whereas muscimol infusion into OFC impaired retention of reversals but not switches. However, whereas training in repeated reversals did not remove the requirement of PL-IL for switch retention (E. L. Rich & M. L. Shapiro, 2007), training in repeated switches did remove the requirement of OFC for reversal retention. Thus, activity during strategy switches was sufficient to initiate learning and remove the requirement of OFC in later reversals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

NMDA and D2-like receptors modulate cognitive flexibility in a color discrimination reversal task in pigeons.

Reversal and extinction learning represent forms of cognitive flexibility that refer to the ability of an animal to alter behavior in response to unanticipated changes on environmental demands. A role for dopamine and glutamate in modulating this behavior has been implicated. Here, we determined the effects of intracerebroventricular injections in pigeons' forebrain of the D2-like receptor agonist quinpirole, the D2-like receptor antagonist sulpiride and the N-methyl-d-aspartate receptor antagonist AP-5 on initial acquisition and reversal of a color discrimination task. On day one, pigeons had to learn to discriminate two color keys. On day two, pigeons first performed a retention test, which was followed by a reversal of the reward contingencies of the two color keys. None of the drugs altered performance in the initial acquisition of color discrimination or affected the retention of the learned color key. In contrast, all drugs impaired reversal learning by increasing trials and incorrect responses in the reversal session. Our data support the hypothesis that D2-like receptor mechanisms, like N-methyl-d-aspartate receptor modulations, are involved in cognitive flexibility and relearning processes, but not in initial learning of stimulus-reward association. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of the anterior cingulate cortex in the control over behavior by Pavlovian conditioned stimuli in rats.

To investigate the contribution of the anterior cingulate cortex (ACC) to stimulus-reward learning, rats with lesions of peri- and postgenual ACC were tested on a variety of Pavlovian conditioning tasks. Lesioned rats learned to approach a food alcove during a stimulus predicting food, and responded normally for conditioned reinforcement. They also exhibited normal conditioned freezing and Pavlovian-instrumental transfer, yet were impaired at autoshaping. To resolve this apparent discrepancy, a further task was developed in which approach to the food alcove was under the control of 2 stimuli, only 1 of which was followed by reward. Lesioned rats were impaired, approaching during both stimuli. It is suggested that the ACC is not critical for stimulus-reward learning per se, but is required to discriminate multiple stimuli on the basis of their association with reward. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Operant learning requires NMDA-receptor activation in the anterior cingulate cortex and dorsomedial striatum, but not in the orbitofrontal cortex.

Previous research has shown that corticostriatal N-methyl-D-aspartate receptor (NMDAR) activation is necessary for operant learning. NMDAR activation induces plasticity-related intracellular signaling processes leading to gene expression, which are hypothesized to be important steps in codifying the content of learning. Operant learning induces immediate early gene (IEG) expression in key corticostriatal structures, namely the dorsomedial striatum (DMS), the orbitofrontal (OFC), and anterior cingulate cortices (ACC). Both the ACC and OFC send glutamatergic projections to the DMS, which is a crucial site for operant behavior. However, the role of NMDAR activation in these corticostriatal regions in operant learning is unknown. To test this hypothesis, the NMDA antagonist AP-5 (1 μg/0.5 μl) or saline was bilaterally microinjected into the ACC, OFC, and DMS of food-deprived rats just prior to operant learning sessions. NMDAR antagonism in the ACC and DMS impaired the acquisition of lever pressing for sucrose pellets but had no effect on lever pressing once learned. NMDAR blockade in OFC did not significantly impair operant learning, suggesting that NMDAR activation in operant learning is site-specific. These data extend our understanding of the role of NMDA receptors in operant learning and behavior throughout an extended corticostriatal network. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Context processing in older adults: Evidence for a theory relating cognitive control to neurobiology in healthy aging.

A theory of cognitive aging is presented in which healthy older adults are hypothesized to suffer from disturbances in the processing of context that impair cognitive control function across multiple domains, including attention, inhibition, and working memory. These cognitive disturbances are postulated to be directly related to age-related decline in the function of the dopamine (DA) system in the prefrontal cortex (PFC). A connectionist computational model is described that implements specific mechanisms for the role of DA and PFC in context processing. The behavioral predictions of the model were tested in a large sample of older (N = 81) and young (N = 175) adults performing variants of a simple cognitive control task that placed differential demands on context processing. Older adults exhibited both performance decrements and, counterintuitively, performance improvements that are in close agreement with model predictions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)