Executive functions in schizophrenia aging: Differential effects of age within specific executive functions.

There are common cognitive and brain abnormalities in schizophrenia and healthy aging which may cumulate in schizophrenia aging. However, the course of executive deficits in late-life schizophrenia is still controversial as it remains unclear whether schizophrenia patients show accelerated aging. The use of specific models of executive functions might help to shed new lights on this issue. The aim of this study was then to determine how each of the four specific executive functions (shifting, updating, inhibition and access to long-term memory) is affected by aging in schizophrenia compared to healthy aging. 20 younger (age 18-34), 17 middle-aged (age 35-49) and 25 older (age 59-76) schizophrenia patients and 62 healthy comparison participants matched for gender, age and education performed a neurocognitive battery evaluating the four specific executive functions. Schizophrenia patients performed worse than comparison participants on shifting, updating and access, whereas inhibition appeared preserved. Age affected the four functions with increased degradation of shifting and access in schizophrenia patients, whereas updating and inhibition showed a normal decline with age. These results suggest a vulnerability of prefrontal and cingulate cortexes in schizophrenia aging. Moreover, as age affected the specific executive functions differently, remediation programs should be adapted to older patients. Models of specific executive functions are useful for understanding the complexity of cognition in schizophrenia and its course during later life so that healthcare can be adapted accordingly.

Retrieval practice improves memory in patients with schizophrenia: new perspectives for cognitive remediation.

BACKGROUND: Schizophrenia is associated with severe cognitive deficits, particularly episodic memory deficits, that interfere with patients' socio-professional functioning. Retrieval practice (also known as testing effect) is a well-established episodic memory strategy that involves taking an initial memory test on a previously learned material. Testing later produces robust long-term memory improvements in comparison to the restudy of the same material both in healthy subjects and in some clinical populations with memory deficits. While retrieval practice might represent a relevant cognitive remediation strategy in patients with schizophrenia, studies using optimal procedures to explore the benefits of retrieval practice in this population are still lacking. Therefore, the purpose of our study was to investigate the benefits of retrieval practice in patients with schizophrenia. METHODS: Nineteen stabilised outpatients with schizophrenia (DSM-5 criteria) and 20 healthy controls first studied a list of 60 word-pairs (30 pairs with weak semantic association and 30 non associated pairs). Half the pairs were studied again (restudy condition), while only the first word of the pair was presented and the subject had to recall the second word for the other half (retrieval practice condition). The final memory test consisted in a cued-recall which took place 2 days later. Statistical analyses were performed using Bayesian methods. RESULTS: Cognitive performances were globally altered in patients. However, in both groups, memory performances for word-pairs were significantly better after retrieval practice than after restudy (56.1% vs 35.7%, respectively, Pr(RP > RS) > 0.999), and when a weak semantic association was present (64.7% vs 27.1%, respectively; Pr(weak > no) > 0.999). Moreover, the positive effect of RP was observed in all patients but one. CONCLUSIONS: Our study is the first to demonstrate that retrieval practice efficiently improves episodic memory in comparison to restudy in patients with schizophrenia. This learning strategy should therefore be considered as a useful tool for cognitive remediation programs. In this perspective, future studies might explore retrieval practice using more ecological material.

Cognitive effects of labeled addictolytic medications.

INTRODUCTION: Alcohol, tobacco, and illegal drug usage is pervasive throughout the world, and abuse of these substances is a major contributor to the global disease burden. Many pharmacotherapies have been developed over the last 50years to target addictive disorders. While the efficacy of these pharmacotherapies is largely recognized, their cognitive impact is less known. However, all substance abuse disorders are known to promote cognitive disorders like executive dysfunction and memory impairment. These impairments are critical for the maintenance of addictive behaviors and impede cognitive behavioral therapies that are regularly administered in association with pharmacotherapies. It is also unknown if addictolytic medications have an impact on preexisting cognitive disorders, and if this impact is modulated by the indication of prescription, i.e. abstinence, reduction or substitution, or by the specific action of the medication. METHOD: We reviewed the cognitive effects of labeled medications for tobacco addiction (varenicline, bupropion, nicotine patch and nicotine gums), alcohol addiction (naltrexone, nalmefene, baclofen, disulfiram, sodium oxybate, acamprosate), and opioid addiction (methadone, buprenorphine) in human studies. Studies were selected following MOOSE guidelines for systematic reviews of observational studies, using the keywords [Cognition] and [Cognitive disorders] and [treatment] for each medication. RESULTS: 971 articles were screened and 77 studies met the inclusion criteria and were reported in this review (for alcohol abuse, n=21, for tobacco n=22, for opioid n=34. However, very few comparative clinical trials have explored the chronic effects of addictolytic medications on cognition in addictive behaviors, and there are no clinical trials on the cognitive impact of nalmefene in patients suffering from alcohol use disorders. DISCUSSION: Although some medications seem to enhance cognition in patients suffering from cognitive disorders, others could promote cognitive impairments, and our work highlights a lack of literature on this subject. In conclusion, more comparative clinical trials are needed to better understand the cognitive impact of addictolytic medications.

Medications between psychiatric and addictive disorders.

INTRODUCTION: Many epidemiological studies have revealed a frequent co-occurrence of psychiatric and substance use disorders. The term used in the literature to refer to this co-occurrence is dual diagnosis. The high prevalence of dual diagnosis has led physicians to observe the effects of medication prescribed to treat psychiatric disorders on the co-occurring substance use disorder and vice versa. The concept of medications between psychiatric and addictive disorders stems from these clinical observations, alongside which, however, it has developed from the observation that both psychiatric and substance use disorders share common neurobiological pathways and trigger common cognitive disorders. This has led researchers to develop medications on the basis of neurobiological and cognitive rationales. MATERIAL AND METHOD: In our article, we review peculiar medications based on neurobiological and cognitive rationales and that have an impact in both psychiatric and addictive disorders. RESULTS: We highlight how interesting these new prescriptions are for clinical observation and for the treatment of patients suffering from dual diagnosis. CONCLUSION: We then go on to discuss the interest in them from the perspective of clinical practice and clinical research, in that the development of medications to treat dual diagnosis helps to further our knowledge of both psychiatric and substance use disorders.

Is retrieval the key? Metamemory judgment and testing as learning strategies.

Re-reading is the most common learning strategy, albeit not a very efficient one. Testing is highly efficient, but not perceived by students as a learning strategy. Prospective judgment-of-learning (JOL) reflect the learner's impression of subsequently being able to retrieve the ongoing learning in a cued-recall task. Estimating JOL involves attempting to retrieve the information, as in testing. The few studies that have explored the potential mnemonic benefit of JOL have yielded contradictory results. Our aim was to compare JOL and testing with re-study and to examine the impact of these strategies according to the relative difficulty of the material (cue-target association strength) in two experiments. After a first encoding phase, participants re-studied, provided JOL, or took a test. Forty-eight hours later, they participated in a final cued-recall test, during which their confidence level judgments were collected. The main result was that delayed JOL behaved in the same way as testing, and both yielded better performances than re-study when material was of moderate difficulty. The easy or very difficult material revealed no differences between these strategies. JOL is proposed as an alternative to testing when faced with difficult material.

Age-related differences in the use of automatic and controlled processes in a situation of sustained attention.

Previous studies examining sustained attention ability in older adults have yielded inconsistent results: age-related decline in studies using traditionally formatted tasks (TFT), in which subjects have to respond to rare targets, and preservation in studies using Go/No-Go tasks, in which subjects have to withhold response to rare targets. The purpose of this study was to examine whether these discrepancies could be explained by a differential use of automatic and controlled processes according to age. To that end, we used two versions of the same task differing in response mode (TFT, Go/No-Go), and the event-related potential (ERP) technique. The within-task comparison first revealed that older adults exhibited a vigilance decrement in the TFT SART, while their performance actually improved in the Go/No-Go SART. Secondly, in both tasks, ERP results notably evidenced increased P2s and non-target P3s in older adults, components related to the allocation of attentional resources. Altogether, our results suggest that in both tasks older adults adopted a controlled processing mode, which resulted in opposite effects on performance according to the nature of the task.

Contextual information influences the feeling of knowing in episodic memory.

The feeling of knowing (FOK) predicts the likelihood of eventually recognizing currently unrecalled items. Koriat (1993, 1995) showed that retrieval of partial target information influences FOK ratings. Building on Koriat's view, the noncriterial-recollection hypothesis contends that contextual information influences FOKs (Brewer, Marsh, Clark-Foos, & Meeks, 2010). Our study assessed the validity of the noncriterial-recollection hypothesis by controlling the amount of potentially-retrievable contextual information presented to participants. We varied the amount of contextual information accompanying the name and image of imaginary animals. There were three information conditions: minimum (name and image), medium (name, image, and country), and maximum (name, image, country, diet and weight). Information condition did not affect recall accuracy. The minimum condition resulted in greater response output (recall and commission errors together). FOKs for unrecalled items were lower in the minimum condition than the other conditions. Consistent with the noncriterial-recollection hypothesis, FOKs were positively correlated with the retrieval of contextual information.

The effects of aging on sustained attention ability: an ERP study.

The aim of this study was to investigate the effects of aging on inhibitory processes and attentional resources in a long-lasting Go/No-Go sustained attention task using the event-related potential (ERP) technique. In line with recent studies, our results showed that older adults were able to maintain sustained attention performance throughout the duration of the task, whereas younger subjects exhibited a vigilance decrement. Regarding ERP results, older adults had larger P2 and Go-P3 amplitudes, components related to resource allocation, suggesting that the older subjects invested more resources in task performance. In addition, the No-Go P3 component, related to inhibitory processes, was more frontally distributed in older than in younger participants. This age-related frontal scalp overrecruitment may have played a compensatory role, enabling older subjects to perform better than younger subjects throughout the duration of the task.

Age-related differences in the recruitment of proactive and reactive control in a situation of sustained attention.

We examined ERP indices of proactive and reactive cognitive control processes in younger and older adults performing a sustained attention Go/No-Go task. Behavioral results showed that older adults were able to maintain a stable level of performance over time, while younger adults exhibited a vigilance decrement. The main ERP findings showed that in older adults, the amplitude of the pre-stimulus slow wave, a marker of proactive control, remained stable with time on task, and that the amplitude of the sustained potential, a marker of reactive control, increased with time on task. On the other hand, in younger adults, the amplitudes of both components decreased over time. Overall, older participants also exhibited larger amplitudes of the error negativity than their younger counterparts. These results suggest that age-related differences in the recruitment of proactive and reactive control over the course of the task can explain age differences in sustained attention performance.

Investigating sustained attention ability in the elderly by using two different approaches: inhibiting ongoing behavior versus responding on rare occasions.

Previous studies on sustained attention ability in the elderly produced inconsistent results. The aim of this study was to evaluate sustained attention performance in younger and older individuals by using, in a within-subjects design, two versions of the same task (the sustained attention to response task, SART) in which only in the response mode differed: in a traditionally formatted task (TFT), subjects had to respond to rare targets, and in a Go/No-Go task they had to withhold response to rare targets. Results showed that in the TFT SART only the older group exhibited a vigilance decrement. On the contrary, only young individuals showed a vigilance decrement in the Go/No-Go SART. These results showed that older individuals, who also reported less mind wandering and a higher level of motivation, exhibited preserved sustained attention ability in the Go/No-Go SART, which could be explained by increased engagement of cognitive control mechanisms in this population. The discrepancy in performance depending on the approach used also underlines the need for further studies on the nature of attention failures and their underlying mechanisms.

Preserved strategic grain-size regulation in memory reporting in patients with schizophrenia.

BACKGROUND: Cognitive and introspection disturbances are considered core features of schizophrenia. In real life, people are usually free to choose which aspects of an event they recall, how much detail to volunteer, and what degree of confidence to impart. Their decision will depend on various situational and personal goals. The authors explored whether schizophrenia patients are able to achieve a compromise between accuracy and informativeness when reporting semantic information. METHODS: Twenty-five patients and 23 healthy matched control subjects answered general knowledge questions requiring numerical answers (how high is the Eiffel tower?), freely at first and then through a metamemory-based control. In the second phase, they answered with respect to two predefined intervals, one narrow and one broad; attributed a confidence judgment to both answers; and afterward selected one of the two answers. Data were analyzed using analyses of variance with group as the between-subjects factor. RESULTS: Patients reported information at a self-paced level of precision less accurately than healthy participants. However, they benefited remarkably from the framing of the response and from the metamemory processes of monitoring and control to the point of improving their memory reporting and matching healthy subjects' accuracy. CONCLUSIONS: In spite of their memory deficit during free reporting, after accuracy monitoring, patients strategically regulated the grain size of their memory reporting and proved able to manage the competing goals of accuracy and informativeness. These results give some cause for optimism as to the possibility for patients to adapt to everyday life situations.

Evidence of some strategic preservation of episodic learning in patients with schizophrenia.

The aim of this study was to gain a better understanding of schizophrenia patients' strategic use of learning time allocation during encoding, and determine whether they are able to use their monitoring and previous performances to adapt their learning behavior efficiently. Schizophrenia is considered to be a pathology of consciousness as well as being associated with impaired awareness of cognitive processes. In this study, after a learning session, individuals may express a Judgment of Learning (JOL), which reflects their sense of being able to retrieve the information later and which forms the basis for their decision whether or not to carry on learning. The introspective abilities of schizophrenia patients and subsequent strategic control of study time during the encoding of easy or difficult word pairs were investigated in 23 patients and 23 healthy comparison subjects. In spite of their memory impairment, patients were able to judge the difficulty of the word pairs with accuracy and adapt their learning time accordingly. Schizophrenia patients are sensitive to difficulty when rating JOLs and afterwards controlling study time. Monitoring their knowledge at the start helped patients to adapt their learning efficiently. These findings may be of value for cognitive remediation.

Metamemory knowledge and beliefs in patients with schizophrenia and how these relate to objective cognitive abilities.

Subjective reports and theories about memory may have an influence on other beliefs and behaviours. Patients with schizophrenia suffer a wide range of deficits affecting their awareness of daily life, including memory. With the Metamemory Inventory in Adulthood (MIA) we ascertained patients' memory knowledge and thoughts about their own cognitive capacities and about several aspects of cognitive functioning: personal capacities, knowledge of processes, use of strategies, perceived change with ageing, anxiety, motivation and mastery. The participants' ratings were correlated with their intellectual, cognitive and psychiatric data. Patients felt they had a lower capacity and marginally lower mastery over their memory than comparison subjects. They reported less recourse to strategies, and higher levels of memory-related anxiety. However, their knowledge of basic memory processes, motivation to succeed, and perception of ageing effects were similar. So patients with schizophrenia do not suffer a general and non specific impairment of their metacognitive knowledge.

Metacognition in schizophrenia: processes underlying patients' reflections on their own episodic memory.

BACKGROUND: The aim of the study was to explore the processes underlying schizophrenia patients' reflections on their own memory. Cognitive deficits and insight problems are considered core symptoms of schizophrenia. Even when people fail to recall a solicited target, they can provide feeling of knowing (FOK) judgments that reflect their ability to judge the accessibility of the target in memory. The metamemory approach allows for direct and experimental quantification of the correspondence between the subjective judgments and the objective measures of memory performance. According to the accessibility hypothesis, FOK evaluations rely on the accessibility of partial and/or contextual information relevant to the memory target. METHODS: The accessibility of partial information relating to a memory target was investigated in 21 patients and 21 healthy comparison subjects matched for age, gender, and level of education. The material to be learned consisted of four-letter nonsense tetragrams, with each letter providing partial information about the four-letter target. RESULTS: The results show that despite memory recall (p < .01) and recognition impairments (p = .02) and lower FOK ratings (p < .05), patients' metamemory judgments increased linearly with the amount of partial information recalled (from one letter to four letters, p < .01). The products of memory retrieval were predictive of both their FOK judgments and their subsequent memory performance. CONCLUSIONS: Schizophrenia patients are as capable as comparison subjects of relying on the products of memory retrieval to monitor accurately their awareness of what they do or do not know. The finding may be of interest for cognitive remediation.

Preserved memory monitoring but impaired memory control during episodic encoding in patients with schizophrenia.

Metamemory awareness refers to the ability to monitor and control how well information is processed depending on the loads and needs of the task at hand. There is some evidence that metamemory functions are impaired in schizophrenia at the time of memory retrieval. This study investigated whether patients with schizophrenia exhibit metamemory abnormalities during the encoding of new information. The frequency of item presentation was varied. Both memory control and memory monitoring were assessed using study-time allocation and Judgments of Learning (JOL), respectively. Repeated items were recalled better by both groups, but memory performance was lower in patients than controls. Patients' behavior patterns were abnormal in terms of the study-time allocated for each item according to presentation frequency. Patients' JOLs were lower than those of controls but remained sensitive to item repetition. Patients' predictive values on memory accuracy were no different to those measured in controls. In addition, none of the patients reported using efficient strategies to help memorize target items. The results show a dissociation between memory control, which was impaired, and memory monitoring, which was spared, in patients with schizophrenia during encoding of new information.

Lorazepam induces multiple disturbances in selective attention: attentional overload, decrement in target processing efficiency, and shifts in perceptual discrimination and response bias.

There is a general consensus that benzodiazepines affect attentional processes, yet only few studies have tried to investigate these impairments in detail. The purpose of the present study was to investigate the effects of a single dose of Lorazepam on performance in a target cancellation task with important time constraints. We measured correct target detections and correct distractor rejections, misses and false positives. The results show that Lorazepam produces multiple kinds of shifts in performance, which suggests that it impairs multipLe processes: (a) the evolution of performance over time was not the same between the placebo and the Lorazepam groups, with the Lorazepam affecting performance quite early after the beginning of the test. This is suggestive of a depletion of attentional resources during sequential attentional processing; (b) Lorazepam affected differently target and distractor processing, with target detection being the most impaired; (c) misses were more frequent under Lorazepam than under placebo, but no such difference was observed as far as false positives were concerned. Signal detection analyses showed that Lorazepam (d) decreased perceptual discrimination, and (e) reliably increased response bias. Our results bring new insights on the multiple effects of Lorazepam on selective attention which, when combined, may have deleterious effects on human performance.

Dissociation between the cognitive process and the phenomenological experience of TOT: effect of the anxiolytic drug lorazepam on TOT states.

TOT states may be viewed as a temporary and reversible microamnesia. We investigated the effects of lorazepam on TOT states in response to general knowledge questions. The lorazepam participants produced more commission errors and more TOTs following commission errors than the placebo participants (although the rates did not change). The resolution of the TOTs was unimpaired by the drug. Neither feeling-of-knowing accuracy nor recognition were affected by lorazepam. The higher level of incorrect recalls produced by lorazepam participants may be due to the fact that they were more frequently temporarily unable to access a known item. For some of these items, the awareness of the retrieval failure resulted in a commission TOT (phenonemological TOT after a commission error). The resolution of the TOT conflict is discussed in the light of the anxiolytic and anticonflict effects of lorazepam. The data are discussed in terms of contemporary theories of TOTs and the effects that benzodiazepines have on semantic memory.

Metamemory in Schizophrenia: an exploration of the feeling-of-knowing state.

The ability to monitor memory performance has considerable importance in everyday life and is among the proposed metamemory dimensions which has been widely investigated. The ability to monitor memory performance accurately was examined in 16 patients with schizophrenia and 16 control subjects by using a Feeling-of-Knowing task on episodic information. Feeling-of-Knowing judgments are predictions made about the likelihood of subsequent recognition of currently non-recallable information. Participants were given cued recall and recognition tests of 50 sentence-target words. Feeling-of-knowing judgments were made for non-recalled targets. Our results first confirm that schizophrenia is associated with episodic memory impairment. By using the Feeling-of-Knowing task, patients with schizophrenia were found to predict accurately their subsequent recognition performance, suggesting an interesting dissociation between a preserved metamemory and an altered memory.

Specific effects of an amnesic drug: effect of lorazepam on study time allocation and on judgment of learning.

We investigated the effects of lorazepam, a benzodiazepine, on the allocation of study time, memory, and judgment of learning, in a cognitive task where the repetition of word presentation was manipulated. The aim was to assess whether lorazepam would affect the learning processes and/or whether the participants would be aware of the amnesic difficulty. A total of 30 healthy volunteers participated in the study, 15 of whom received a capsule containing the lorazepam drug (0.038 mg/kg) and 15 a placebo capsule. First, the accuracy of delayed judgments of learning (JOL) was measured in both groups. For the JOL ratings, results showed that all the participants benefited from word repetition. Although the overall performance was lower in the lorazepam than in the placebo group, the accuracy of the JOL ratings was preserved by the drug. Second, all the participants benefited from the repetition of learning, although the performances of the lorazepam-treated subjects remained lower than those of the placebo participants. The repetition of learning had an effect on JOL in both groups. Finally, the time spent learning each (allocation study time) pair of words was measured. For the placebo group, results revealed that study time decreased significantly with the frequency of presentation. For the lorazepam group, no effect of presentation frequency was found. Overall, our findings suggest that the lorazepam drug has a differential effect on the monitoring and the control processes involved in a learning task. The implications of these findings are discussed within the theoretical framework of metacognition.

Benzodiazepines and semantic memory: effects of lorazepam on the Moses illusion.

RATIONALE: When asked "How many animals of each kind did Moses take on the ark?", people fail to notice the distortion introduced by the impostor "Moses" and respond "two". It has been argued that the effect must be due to the existence of a partial-match process. In most situations, the form of a question is not likely to closely match the memory representation it queries. Thus, for the partial match hypothesis people ignore some semantic distortions. In the same vein, it has been shown that the benzodiazepine lorazepam drug induces some impairments of semantic memory as participants under lorazepam provide more incorrect recalls than placebo do with general information questions. OBJECTIVES: The aim of this study was to investigate the effects of the benzodiazepine lorazepam on the Moses illusion paradigm. METHOD: The effects of lorazepam (0.038 mg/kg) and of a placebo were investigated in 28 healthy volunteers. Twenty-two illusory questions were presented along with 72 normal general information questions. RESULTS: Lorazepam impaired the ability to detect the Moses illusion. Moreover, lorazepam participants appeared less biased to consider a question distorted than placebo participants. CONCLUSIONS: The temporary and reversible semantic memory impairments experienced by participants when falling into the Moses illusion are more frequent under lorazepam. The amnesic drug lorazepam may impair semantic processing as well as the strategic control of memory.