Dissociable effects of 5-HT2C receptor antagonism and genetic inactivation on perseverance and learned non-reward in an egocentric spatial reversal task

Cognitive flexibility can be assessed in reversal learning tests, which are sensitive to modulation of 5-HT2C receptor (5-HT2CR) function. Successful performance in these tests depends on at least two dissociable cognitive mechanisms which may separately dissipate associations of previous positive and negative valence. The first is opposed by perseverance and the second by learned non-reward. The current experiments explored the effect of reducing function of the 5-HT2CR on the cognitive mechanisms underlying egocentric reversal learning in the mouse. Experiment 1 used the 5-HT2CR antagonist SB242084 (0.5 mg/kg) in a between-groups serial design and Experiment 2 used 5-HT2CR KO mice in a repeated measures design. Animals initially learned to discriminate between two egocentric turning directions, only one of which was food rewarded (denoted CS+, CS−), in a T- or Y-maze configuration. This was followed by three conditions; (1) Full reversal, where contingencies reversed; (2) Perseverance, where the previous CS+ became CS− and the previous CS− was replaced by a novel CS+; (3) Learned non-reward, where the previous CS− became CS+ and the previous CS+ was replaced by a novel CS-. SB242084 reduced perseverance, observed as a decrease in trials and incorrect responses to criterion, but increased learned non-reward, observed as an increase in trials to criterion. In contrast, 5-HT2CR KO mice showed increased perseverance. 5-HT2CR KO mice also showed retarded egocentric discrimination learning. Neither manipulation of 5-HT2CR function affected performance in the full reversal test. These results are unlikely to be accounted for by increased novelty attraction, as SB242084 failed to affect performance in an unrewarded novelty task. In conclusion, acute 5-HT2CR antagonism and constitutive loss of the 5-HT2CR have opposing effects on perseverance in egocentric reversal learning in mice. It is likely that this difference reflects the broader impact of 5HT2CR loss on the development and maintenance of cognitive function

BOLD Correlates of Trial-by-Trial Reaction Time Variability in Gray and White Matter: A Multi-Study fMRI Analysis

Reaction time (RT) is one of the most widely used measures of performance in experimental psychology, yet relatively few fMRI studies have included trial-by-trial differences in RT as a predictor variable in their analyses. Using a multi-study approach, we investigated whether there are brain regions that show a general relationship between trial-by-trial RT variability and activation across a range of cognitive tasks.The relation between trial-by-trial differences in RT and brain activation was modeled in five different fMRI datasets spanning a range of experimental tasks and stimulus modalities. Three main findings were identified. First, in a widely distributed set of gray and white matter regions, activation was delayed on trials with long RTs relative to short RTs, suggesting delayed initiation of underlying physiological processes. Second, in lateral and medial frontal regions, activation showed a "time-on-task" effect, increasing linearly as a function of RT. Finally, RT variability reliably modulated the BOLD signal not only in gray matter but also in diffuse regions of white matter.The results highlight the importance of modeling trial-by-trial RT in fMRI analyses and raise the possibility that RT variability may provide a powerful probe for investigating the previously elusive white matter BOLD signal

Processing of inconsistent emotional information: an fMRI study

Previous studies investigating the anterior cingulate cortex (ACC) have relied on a number of tasks which involved cognitive control and attentional demands. In this fMRI study, we tested the model that ACC functions as an attentional network in the processing of language. We employed a paradigm that requires the processing of concurrent linguistic information predicting that the cognitive costs imposed by competing trials would engender the activation of ACC. Subjects were confronted with sentences where the semantic content conflicted with the prosodic intonation (CONF condition) randomly interspaced with sentences which conveyed coherent discourse components (NOCONF condition). We observed the activation of the rostral ACC and the middle frontal gyrus when the NOCONF condition was subtracted from the CONF condition. Our findings provide evidence for the involvement of the rostral ACC in the processing of complex competing linguistic stimuli, supporting theories that claim its relevance as a part of the cortical attentional circuit. The processing of emotional prosody involved a bilateral network encompassing the superior and medial temporal cortices. This evidence confirms previous research investigating the neuronal network that supports the processing of emotional information

Priming Picture Naming with a Semantic Task: An fMRI Investigation

Prior semantic processing can enhance subsequent picture naming performance, yet the neurocognitive mechanisms underlying this effect and its longevity are unknown. This functional magnetic resonance imaging study examined whether different neurological mechanisms underlie short-term (within minutes) and long-term (within days) facilitation effects from a semantic task in healthy older adults. Both short- and long-term facilitated items were named significantly faster than unfacilitated items, with short-term items significantly faster than long-term items. Region of interest results identified decreased activity for long-term facilitated items compared to unfacilitated and short-term facilitated items in the mid-portion of the middle temporal gyrus, indicating lexical-semantic priming. Additionally, in the whole brain results, increased activity for short-term facilitated items was identified in regions previously linked to episodic memory and object recognition, including the right lingual gyrus (extending to the precuneus region) and the left inferior occipital gyrus (extending to the left fusiform region). These findings suggest that distinct neurocognitive mechanisms underlie short- and long-term facilitation of picture naming by a semantic task, with long-term effects driven by lexical-semantic priming and short-term effects by episodic memory and visual object recognition mechanisms

Exploring Predictors of Outcome in the Psychosis Prodrome: Implications for Early Identification and Intervention

Functional disability is a key component of many psychiatric illnesses, particularly schizophrenia. Impairments in social and role functioning are linked to cognitive deficits, a core feature of psychosis. Retrospective analyses demonstrate that substantial functional decline precedes the onset of psychosis. Recent investigations reveal that individuals at clinical-high-risk (CHR) for psychosis show impairments in social relationships, work/school functioning and daily living skills. CHR youth also demonstrate a pattern of impairment across a range of cognitive domains, including social cognition, which is qualitatively similar to that of individuals with schizophrenia. While many studies have sought to elucidate predictors of clinical deterioration, specifically the development of schizophrenia, in such CHR samples, few have investigated factors relevant to psychosocial outcome. This review integrates recent findings regarding cognitive and social-cognitive predictors of outcome in CHR individuals, and proposes potential directions for future research that will contribute to targeted interventions and improved outcome for at-risk youth

Cognitive function during early abstinence from opioid dependence: a comparison to age, gender, and verbal intelligence matched controls

BACKGROUND: Individuals with opioid dependence have cognitive deficits during abuse period in attention, working memory, episodic memory, and executive function. After protracted abstinence consistent cognitive deficit has been found only in executive function. However, few studies have explored cognitive function during first weeks of abstinence. The purpose of this study was to study cognitive function of individuals with opioid dependence during early abstinence. It was hypothesized that cognitive deficits are pronounced immediately after peak withdrawal symptoms have passed and then partially recover. METHODS: Fifteen patients with opioid dependence and fifteen controls matched for, age, gender, and verbal intelligence were tested with a cognitive test battery When patients performed worse than controls correlations between cognitive performance and days of withdrawal, duration of opioid abuse, duration of any substance abuse, or opioid withdrawal symptom inventory score (Short Opiate Withdrawal Scale) were analyzed. RESULTS: Early abstinent opioid dependent patients performed statistically significantly worse than controls in tests measuring complex working memory, executive function, and fluid intelligence. Their complex working memory and fluid intelligence performances correlated statistically significantly with days of withdrawal. CONCLUSION: The results indicate a rather general neurocognitive deficit in higher order cognition. It is suggested that cognitive deficit during early abstinence from opioid dependence is related to withdrawal induced neural dysregulation in the prefrontal cortex and is partly transient

Somatosensory System Deficits in Schizophrenia Revealed by MEG during a Median-Nerve Oddball Task

Although impairments related to somatosensory perception are common in schizophrenia, they have rarely been examined in functional imaging studies. In the present study, magnetoencephalography (MEG) was used to identify neural networks that support attention to somatosensory stimuli in healthy adults and abnormalities in these networks in patient with schizophrenia. A median-nerve oddball task was used to probe attention to somatosensory stimuli, and an advanced, high-resolution MEG source-imaging method was applied to assess activity throughout the brain. In nineteen healthy subjects, attention-related activation was seen in a sensorimotor network involving primary somatosensory (S1), secondary somatosensory (S2), primary motor (M1), pre-motor (PMA), and paracentral lobule (PCL) areas. A frontal–parietal–temporal “attention network”, containing dorsal- and ventral–lateral prefrontal cortex (DLPFC and VLPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), superior parietal lobule (SPL), inferior parietal lobule (IPL)/supramarginal gyrus (SMG), and temporal lobe areas, was also activated. Seventeen individuals with schizophrenia showed early attention-related hyperactivations in S1 and M1 but hypo-activation in S1, S2, M1, and PMA at later latency in the sensorimotor network. Within this attention network, hypoactivation was found in SPL, DLPFC, orbitofrontal cortex, and the dorsal aspect of ACC. Hyperactivation was seen in SMG/IPL, frontal pole, and the ventral aspect of ACC in patients. These findings link attention-related somatosensory deficits to dysfunction in both sensorimotor and frontal–parietal–temporal networks in schizophrenia