Impairments in learning by monetary rewards and alcohol-associated rewards in detoxified alcoholic patients.

BACKGROUND: Excessive alcohol consumption has been linked to structural and functional brain changes associated with cognitive, emotional, and behavioral impairments. It has been suggested that neural processing in the reward system is also affected by alcoholism. The present study aimed at further investigating reward-based associative learning and reversal learning in detoxified alcohol-dependent patients. METHODS: Twenty-one detoxified alcohol-dependent patients and 26 healthy control subjects participated in a probabilistic learning task using monetary and alcohol-associated rewards as feedback stimuli indicating correct responses. Performance during acquisition and reversal learning in the different feedback conditions was analyzed. RESULTS: Alcohol-dependent patients and healthy control subjects showed an increase in learning performance over learning blocks during acquisition, with learning performance being significantly lower in alcohol-dependent patients. After changing the contingencies, alcohol-dependent patients exhibited impaired reversal learning and showed, in contrast to healthy controls, different learning curves for different types of rewards with no increase in performance for high monetary and alcohol-associated feedback. CONCLUSIONS: The present findings provide evidence that dysfunctional processing in the reward system in alcohol-dependent patients leads to alterations in reward-based learning resulting in a generally reduced performance. In addition, the results suggest that alcohol-dependent patients are, in particular, more impaired in changing an established behavior originally reinforced by high rewards.

Comorbid substance use disorder in schizophrenia: a selective overview of neurobiological and cognitive underpinnings.

Although individuals with schizophrenia show a lifetime prevalence of 50% for suffering from a comorbid substance use disorder, substance abuse usually represents an exclusion criterion for studies on schizophrenia. This implies that surprisingly little is known about a large group of patients who are particularly difficult to treat. The aim of the present work is to provide a brief and non-exhaustive overview of the current knowledgebase about neurobiological and cognitive underpinnings for dual diagnosis schizophrenia patients. Studies published within the last 20 years were considered using computerized search engines. The focus was on nicotine, caffeine, alcohol, cannabis and cocaine being among the most common substances of abuse. All drugs of abuse target dopaminergic, glutamatergic and GABAergic transmission which are also involved in the pathophysiology of schizophrenia. Current literature suggests that neurocognitive function might beless disrupted in substance-abusing compared to non-abusing schizophrenia patients, but in particular the neuroimaging database on this topic is sparse. Detrimental effects on brain structure and function were shown for patients for whom alcohol is the main substance of abuse. It is as yet unclear whether this finding might be an artifact of age differences of patient subgroups with different substance abuse patterns. More research is warranted on the specific neurocognitive underpinnings of schizophrenia patients abusing distinct psychoactive substances. Treatment programs might either benefit from preserved cognitive function as a resource or specifically target cognitive impairment in different subgroups of addicted schizophrenia patients.

The involvement of the thalamus in semantic retrieval: a clinical group study.

There is increasing attention about the role of the thalamus in high cognitive functions, including memory. Although the bulk of the evidence refers to episodic memory, it was recently proposed that the mediodorsal (MD) and the centromedian-parafascicular (CM-Pf) nuclei of the thalamus may process general operations supporting memory performance, not only episodic memory. This perspective agrees with other recent fMRI findings on semantic retrieval in healthy participants. It can therefore be hypothesized that lesions to the MD and the CM-Pf impair semantic retrieval. In this study, 10 patients with focal ischemic lesions in the medial thalamus and 10 healthy controls matched for age, education, and verbal IQ performed a verbal semantic retrieval task. Patients were assigned to a target clinical group and a control clinical group based on lesion localization. Patients did not suffer from aphasia and performed in the range of controls in a categorization and a semantic association task. However, target patients performed poorer than healthy controls on semantic retrieval. The deficit was not because of higher distractibility but of an increased rate of false recall and, in some patients, of a considerably increased rate of misses. The latter deficit yielded a striking difference between the target and the control clinical groups and is consistent with anomia. Follow-up high-resolution structural scanning session in a subsample of patients revealed that lesions in the CM-Pf and MD were primarily associated with semantic retrieval deficits. We conclude that integrity of the MD and the CM-Pf is required for semantic retrieval, possibly because of their role in the activation of phonological representations.

Neural representations of unfamiliar objects are modulated by sensorimotor experience.

Sensory/functional accounts of semantic memory organization emphasize that object representations in the brain reflect the modalities involved in object knowledge acquisition. The present study aimed to elucidate the impact of different types of object-related sensorimotor experience on the neural representations of novel objects. Sixteen subjects engaged in an object matching task while their brain activity was assessed with functional magnetic resonance imaging (fMRI), before and after they acquired knowledge about previously unfamiliar objects. In three training sessions subjects learned about object function, actively manipulating only one set of objects (manipulation training objects, MTO), and visually exploring a second set (visual training objects, VTO). A third object set served as control condition and was not part of the training (no training objects, NTO). While training-related activation increases were observed in the fronto-parietal cortex for both VTO and MTO, post training activity in the left inferior/middle frontal gyrus and the left posterior inferior parietal lobule was higher for MTO than VTO and NTO. As revealed by Dynamic Causal Modeling of effective connectivity between the regions with enhanced post training activity, these effects were likely caused, respectively, by a down-regulation of a fronto-parietal tool use network in response to VTO, and by an increased connectivity for MTO. This pattern of findings indicates that the modalities involved in sensorimotor experience influence the formation of neural representations of objects in semantic memory, with manipulation experience specifically yielding higher activity in regions of the fronto-parietal cortex.

Cortical processing of saccade-related efference copy signals in patients with cerebellar lesion.

The updating of visual space across saccades is thought to rely on efference copies of motor commands. In humans, thalamic lesions impair performance on a saccadic double-step task, which requires the use of efference copy information, and the altering of saccade-related efference copy processing. This deficit is attributed to disruption of a pathway from the superior colliculus to the frontal eye field. However, the cerebellum is probably also involved in efference copy processing, due to its pivotal role for predictive motor control. The present study investigated the processing of efference copy information in eight patients with focal cerebellar lesions and 22 healthy controls by means of a saccadic double-step task with simultaneous event-related potential recording. Despite intact behavioural performance, a positive event-related potential component between 150 and 450 ms after first saccade onset in the updating condition, which has been interpreted in terms of the integration of efference copy signals with motor intentions for a subsequent saccade, was markedly reduced in the patients. These findings suggest that the cerebellum contributes to on-line saccade monitoring, and that cerebellar lesions alter saccade-related efference copy processing. However, given the intact behavioural performance, the reduced positivity in the patients may indicate that cerebellar damage is accounted for by either exploiting reduced saccade-related information, or making use of compensatory strategies to circumvent a deficit in using efference copy information procured by the cerebellum. The present study extends previous findings on the neural underpinnings of saccadic updating and further elucidates the mechanisms underlying cerebellar predictive motor control.

Updating of visual space across horizontal saccades in cerebellar and thalamic lesion patients.

Efference copies of motor commands are used to update visual space across saccades, ultimately ensuring transsaccadic constancy of space. Thalamic lesions have been shown to impair efference copy-based saccadic updating in an oculomotor context, i.e., when two successive saccades are required. Moreover, the cerebellum has also been discussed as one possible source of saccade-related efference copy signals. The present study aimed to investigate the effects of thalamic and cerebellar lesions on saccadic updating in a perceptual context. To this end, seven patients with focal cerebellar lesions, seven patients with focal thalamic lesions and 11 healthy controls completed a perceptual localisation task in which the position of a target had to be updated across a single horizontal saccade, while saccade-related event-related potentials (ERPs) were recorded. Contrary to the expectations, localisation precision in both patient groups did not differ from the respective controls. A positive ERP component with centroparietal distribution occurring from about 300 to 500 ms after saccade onset in the updating condition was observed equally pronounced in controls and thalamic lesion patients. In cerebellar lesion patients, there was evidence of a reduction of this relative positivity in the updating condition, particularly for leftward saccades. This finding suggests that cerebellar damage altered the neural processes underlying saccadic updating in a perceptual context without causing overt behavioural deficits.

Perception of affective prosody in patients at an early stage of relapsing-remitting multiple sclerosis.

Cognitive dysfunction is well known in patients suffering from multiple sclerosis (MS) and has been described for many years. Cognitive impairment, memory, and attention deficits seem to be features of advanced MS stages, whereas depression and emotional instability already occur in early stages of the disease. However, little is known about processing of affective prosody in patients in early stages of relapsing-remitting MS (RRMS). In this study, tests assessing attention, memory, and processing of affective prosody were administered to 25 adult patients with a diagnosis of RRMS at an early stage and to 25 healthy controls (HC). Early stages of the disease were defined as being diagnosed with RRMS in the last 2 years and having an Expanded Disability Status Scale (EDSS) of 2 or lower. Patients and HC were comparable in intelligence quotient (IQ), educational level, age, handedness, and gender. Patients with early stages of RRMS performed below the control group with respect to the subtests 'discrimination of affective prosody' and 'matching of affective prosody to facial expression' for the emotion 'angry' of the 'Tübingen Affect Battery'. These deficits were not related to executive performance. Our findings suggest that emotional prosody comprehension is deficient in young patients with early stages of RRMS. Deficits in discriminating affective prosody early in the disease may make misunderstandings and poor communication more likely. This might negatively influence interpersonal relationships and quality of life in patients with RRMS.

Theory of mind and empathy in patients at an early stage of relapsing remitting multiple sclerosis.

INTRODUCTION: Early after having been diagnosed with relapsing remitting multiple sclerosis (RRMS), young patients coping with the new situation require good social support and interactions. Successful social interaction is critically dependent upon the ability to understand the minds of others and their feelings. Social cognition refers to the ability to understand the mind of others. Theory of mind (ToM) defines the capability to reason about mental states of others. Empathy describes the ability to have insight into emotional stages and feelings of others. Despite the knowledge of cognitive impairment, which can have profound effects on patients daily activities and quality of life in advanced stages of multiple sclerosis, little is known concerning social cognition in early stages of RRMS. METHODS: In this analysis, tests assessing executive functions (working memory, set shifting and inhibition) and instruments measuring theory of mind (the Movie for the Assessment of Social Cognition - MASC) and empathy (Baron-Cohen's Empathy Quotient) were administered to 25 young adult patients at an early stage of RRMS and to 25 healthy controls (HC). Patients and HC were carefully matched according to intellectual level, age, gender, handedness and education. An early stage of the disease was defined as being diagnosed with RRMS in the last 2 years and having an EDSS of 2 or lower. RESULTS: Patients had significantly more incorrect responses ("missing") ToM (P<0.04). Moreover, patients showed a significantly lower level of empathy in the self-rating questionnaire (P<0.02). Of the cognitive tests and depression, ToM and Empathy Quotient (EQ) scores were only significantly correlated with the interference score of the stroop test. CONCLUSIONS: Our findings suggest that theory of mind and empathy are deficient even at early stages of RRMS. Deficits in theory of mind and empathy might negatively influence interpersonal relationships in patients with RRMS.

Recall deficits in stroke patients with thalamic lesions covary with damage to the parvocellular mediodorsal nucleus of the thalamus.

The functional role of the mediodorsal thalamic nucleus (MD) and its cortical network in memory processes is discussed controversially. While Aggleton and Brown (1999) suggested a role for recognition and not recall, Van der Werf et al. (2003) suggested that this nucleus is functionally related to executive function and strategic retrieval, based on its connections to the prefrontal cortices (PFC). The present study used a lesion approach including patients with focal thalamic lesions to examine the functions of the MD, the intralaminar nuclei and the midline nuclei in memory processing. A newly designed pair association task was used, which allowed the assessment of recognition and cued recall performance. Volume loss in thalamic nuclei was estimated as a predictor for alterations in memory performance. Patients performed poorer than healthy controls on recognition accuracy and cued recall. Furthermore, patients responded slower than controls specifically on recognition trials followed by successful cued recall of the paired associate. Reduced recall of picture pairs and increased response times during recognition followed by cued recall covaried with the volume loss in the parvocellular MD. This pattern suggests a role of this thalamic region in recall and thus recollection, which does not fit the framework proposed by Aggleton and Brown (1999). The functional specialization of the parvocellular MD accords with its connectivity to the dorsolateral PFC, highlighting the role of this thalamocortical network in explicit memory (Van der Werf et al., 2003).

Learning from positive and negative monetary feedback in patients with alcohol dependence.

BACKGROUND: Chronic and excessive consumption of alcohol is associated with structural, physiological, and functional changes in multiple regions of the human brain including the prefrontal cortex, the medial temporal lobe, and the structures of the reward system. The present study aimed to assess the ability of alcohol-dependent patients (ADP) to learn probabilistic stimulus-reward contingencies and to transfer the acquired knowledge to new contexts. During transfer, the relative preference to learn from positive or negative feedback was also assessed. METHODS: Twenty-four recently detoxified ADP and 20 healthy controls engaged in a feedback learning task with monetary rewards. The learning performance per se and transfer performance including positive versus negative learning were examined, as well as the relationship between different learning variables and variables comprising alcohol and nicotine consumption patterns, depression, and personality traits (harm avoidance and impulsivity). RESULTS: Patients did not show a significant general learning deficit in the acquisition of stimulus-response-outcome associations. Fifteen healthy subjects and 13 patients reached the transfer phase, in which ADP showed generally lower performance than healthy controls. There was no specific deficit with regard to learning from positive or negative feedback. The only near-significant (negative) correlation between learning variables and drug consumption patterns, depression, and personality traits emerged for harm avoidance and positive learning in controls. CONCLUSIONS: Impaired transfer performance suggests that ADP had problems applying their acquired knowledge in a new context. Potential relations to dysfunctions of specific brain structures and implications of the finding for therapy are discussed.

Cerebellar lesions alter performance monitoring on the antisaccade task--an event-related potentials study.

Error processing is associated with distinct event-related potential components (ERPs), i.e. the error-related negativity (ERN) which occurs within approximately 150 ms and is typically more pronounced than the correct-response negativity (CRN), and the error positivity (Pe) emerging from about 200 to 400 ms after an erroneous response. The short latency of the ERN suggests that the internal error monitoring system acts on rapidly available central information such as an efference copy signal rather than slower peripheral feedback. The cerebellum has been linked to an internal forward-model which enables online performance monitoring by predicting the sensory consequences of actions, most probably by making use of efference copies. In the present study it was hypothesized that the cerebellum is involved in the fast evaluation of saccadic response accuracy as reflected by the ERN. Error processing on an antisaccade task was investigated in eight patients with focal vascular lesions to the cerebellum and 22 control subjects using ERPs. While error rates were comparable between groups, saccadic reaction times (SRTs) were enhanced in the patients, and the error-correct difference waveforms showed reduced amplitudes for patients relative to controls in the ERN time window. Notably, this effect was mainly driven by an increased CRN in the patients. In the later Pe time window, the difference signal yielded higher amplitudes in patients compared to controls mainly because of smaller Pe amplitudes on correct trials in patients. The altered ERN/CRN pattern suggests that the cerebellum is critically involved in fast classification of saccadic accuracy. Largely intact performance accuracy together with increased SRTs and the altered Pe pattern may indicate a compensatory mechanism presumably related to slower, more conscious aspects of error processing in the patients.

Human memory manipulated: dissociating factors contributing to MTL activity, an fMRI study.

Memory processes are mainly studied with subjective rating procedures. We used a morphing procedure to objectively manipulate the similarity of target stimuli. While undergoing functional magnetic resonance imaging, nineteen subjects performed a encoding and recognition task on face and scene stimuli, varying the degree of manipulation of previously studied targets at 0%, 20%, 40% or 60%. Analyses were performed with parametric modulations for objective stimulus status (morphing level), subjective memory (confidence rating), and reaction times (RTs). Results showed that medial temporal lobe (MTL) activity can be best explained by a combination of subjective and objective factors. Memory success is associated with activity modulation in the hippocampus both for faces and for scenes. Memory failures correlated with lower hippocampal activity for scenes, but not for faces. Activity changed during retrieval on similar areas activated during encoding. There was a considerable impact of RTs on memory-related areas. Objective perceptual identity correlated with activity in the left MTL, while subjective memory experience correlated with activity in the right MTL for both types of material. Overall, the results indicate that MTL activity is heterogeneous, showing both linear and non-linear activity, depending on the factor analyzed.

Eyeblink conditional discrimination learning in healthy young men is impaired after stress exposure.

Stress is known to influence the hippocampus. Eyeblink conditional discrimination learning is dependent on the hippocampus, but the effects of stress on the task are unknown. Male participants were allocated to a psychosocial stress condition (Trier Social Stress Test) or a control condition. Afterwards, a conditional discrimination task was performed. A tone (the CS) predicted an airpuff (the US) only when preceded by a specific visual stimulus (a red or a green colored square, the S+ and S-). Stressed participants showed a rise in cortisol and an increase in negative affect. Stressed participants also failed to acquire the conditional discrimination. They responded to all of the presented CS irrespective of the preceding occasion setter (S+ or S-). Controls, in contrast, acquired the discrimination rapidly. The present study provides further evidence for an impairing effect of acute stress on tasks relying on the hippocampal formation.

Face and body perception in schizophrenia: a configural processing deficit?

Face and body perception rely on common processing mechanisms and activate similar but not identical brain networks. Patients with schizophrenia show impaired face perception, and the present study addressed for the first time body perception in this group. Seventeen patients diagnosed with schizophrenia or schizoaffective disorder were compared to 17 healthy controls on standardized tests assessing basic face perception skills (identity discrimination, memory for faces, recognition of facial affect). A matching-to-sample task including emotional and neutral faces, bodies and cars either in an upright or in an inverted position was administered to assess potential category-specific performance deficits and impairments of configural processing. Relative to healthy controls, schizophrenia patients showed poorer performance on the tasks assessing face perception skills. In the matching-to-sample task, they also responded more slowly and less accurately than controls, regardless of the stimulus category. Accuracy analysis showed significant inversion effects for faces and bodies across groups, reflecting configural processing mechanisms; however reaction time analysis indicated evidence of reduced inversion effects regardless of category in schizophrenia patients. The magnitude of the inversion effects was not related to clinical symptoms. Overall, the data point towards reduced configural processing, not only for faces but also for bodies and cars in individuals with schizophrenia.

Mechanisms of cerebellar contributions to cognition in humans.

The role of the human cerebellum in cognitive processes is the subject of ongoing debate. On the basis of neuroanatomical findings of closed cerebro-cerebellar loops in monkeys, which originate not only in motor but also in nonmotor regions of the cerebral cortex, this article addresses mechanisms of the involvement of the human cerebellum in two well-studied cognitive domains, executive function, working memory in particular, and associative learning, with special emphasis on the nature of a potential cerebellar contribution to these cognitive processes. The uniform organization of cortico-cerebellar connections suggests parallels in cerebellar information processing in motor- and nonmotor contexts. Taking into account recent models on cerebellar function, it is suggested that the main contribution of the cerebellum to motor as well as to cognitive tasks may be to provide accurate predictions of future sensations, actions, and events. WIREs Cogn Sci 2012, 3:171-184. doi: 10.1002/wcs.1161 For further resources related to this article, please visit the WIREs website.

Positivity effect in healthy aging in observational but not active feedback-learning.

The present study investigated the impact of healthy aging on the bias to learn from positive or negative performance feedback in observational and active feedback learning. In active learning, a previous study had already shown a negative learning bias in healthy seniors older than 75 years, while no bias was found for younger seniors. However, healthy aging is accompanied by a 'positivity effect', a tendency to primarily attend to stimuli with positive valence. Based on recent findings of dissociable neural mechanisms in active and observational feedback learning, the positivity effect was hypothesized to influence older participants' observational feedback learning in particular. In two separate experiments, groups of young (mean age 27) and older participants (mean age 60 years) completed an observational or active learning task designed to differentially assess positive and negative learning. Older but not younger observational learners showed a significant bias to learn better from positive than negative feedback. In accordance with previous findings, no bias was found for active learning. This pattern of results is discussed in terms of differences in the neural underpinnings of active and observational learning from performance feedback.

The feedback-related negativity is modulated by feedback probability in observational learning.

The feedback-related negativity (FRN), an event-related potentials (ERPs) component reflecting activity of the anterior cingulate cortex (ACC), has been shown to be modulated by feedback expectancy following active choices in feedback-based learning tasks. A general reduction of FRN amplitude has been described in observational feedback learning, raising the question whether FRN amplitude is modulated in a similar way in this type of learning. The present study investigated whether the FRN and the P300 - a second ERP component related to feedback processing - are modulated by feedback probability in observational learning. Thirty-two subjects participated in the experiment. They observed a virtual person choosing between two symbols and receiving positive or negative feedback. Learning about stimulus-specific feedback probabilities was assessed in active test trials without feedback. In addition, the bias to learn from positive or negative feedback and - in a subsample of 17 subjects - empathy scores were obtained. General FRN and P300 modulations by feedback probability were found across all subjects. Only for the FRN in learners, an interaction between probability and valence was observed. Larger FRN amplitudes for negative relative to positive feedback only emerged for the lowest outcome probability. The results show that feedback expectancy modulates FRN amplitude also in observational learning, suggesting a similar ACC function as in active learning. On the other hand, the modulation is only seen for very low feedback expectancy, which suggests that brain regions other than those of the reward system contribute to feedback processing in an observation setting.

Cognitive and affective empathy in depression linked to executive control.

Depression has been linked to executive dysfunction and emotion recognition impairments, associated with abnormalities in fronto-temporal and subcortical brain regions. Little is known about changes of different empathy subcomponents during depression, with potential impairments being related to the interpersonal difficulties of depressed patients. Twenty patients treated for an episode of unipolar depression and 20 matched healthy controls were assessed. Measures of dispositional and behavioural empathy components were administered along with tests of cognitive flexibility, response inhibition and working memory. Relative to controls, depressed patients showed higher self-reported dispositional empathy scores, mainly driven by increased personal distress scores. Patients and controls did not differ significantly in terms of behavioural cognitive empathy, empathic concern and personal affective involvement or in their executive function performance. In the patients, cognitive flexibility and response inhibition accuracy were associated with behavioural empathy. While an increased disposition towards feeling personal distress in response to other people's suffering seems to be in generally related to depressive symptoms, behavioural empathy might depend on the functional integrity of executive control during an episode of clinical depression. Impairments in this regard could contribute to the interpersonal difficulties depressed patients are frequently faced with which might have important implications for treatment.

Altered error processing following vascular thalamic damage: evidence from an antisaccade task.

Event-related potentials (ERP) research has identified a negative deflection within about 100 to 150 ms after an erroneous response--the error-related negativity (ERN)--as a correlate of awareness-independent error processing. The short latency suggests an internal error monitoring system acting rapidly based on central information such as an efference copy signal. Studies on monkeys and humans have identified the thalamus as an important relay station for efference copy signals of ongoing saccades. The present study investigated error processing on an antisaccade task with ERPs in six patients with focal vascular damage to the thalamus and 28 control subjects. ERN amplitudes were significantly reduced in the patients, with the strongest ERN attenuation being observed in two patients with right mediodorsal and ventrolateral and bilateral ventrolateral damage, respectively. Although the number of errors was significantly higher in the thalamic lesion patients, the degree of ERN attenuation did not correlate with the error rate in the patients. The present data underline the role of the thalamus for the online monitoring of saccadic eye movements, albeit not providing unequivocal evidence in favour of an exclusive role of a particular thalamic site being involved in performance monitoring. By relaying saccade-related efference copy signals, the thalamus appears to enable fast error processing. Furthermore early error processing based on internal information may contribute to error awareness which was reduced in the patients.

What comes first? Electrophysiological differences in the temporal course of memory and future thinking.

It is now widely accepted that remembering the past and imagining the future rely on a number of shared processes and recruit a similar set of brain regions. However, memory and future thinking place different demands on a range of processes. For instance, although remembering should lead to early associative retrieval of event details, event construction may be slower for future events, for which details from different memories are combined. In order to shed light on the question of how the brain distinguishes between memories and future thoughts, we investigated the differences in the electrophysiological correlates of the vivid elaboration of future and past events. In the slow cortical potentials of 24 healthy human participants, differences during early elaboration were observed at temporo-parietal and parieto-occipital electrode sites, presumably reflecting differential recruitment of sensory and semantic detail retrieval. Additional differences emerged over the right pre-frontal cortex during later elaboration, which could be linked to differential retrieval demands. In conclusion, the time course differences, which presumably reflect the varying recruitment of sub-processes engaged during mental time travel, will help to understand the mechanisms with which the brain separates memories from future thoughts.