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Auditory recognition memory, conscious recollection, and executive function in patients with schizophrenia.

BACKGROUND: Dual-process models propose that recognition memory (RM) involves two processes: conscious recollection and familiarity-aware memory. Studies investigating RM in schizophrenia report a selective deficit in conscious recollection and intact levels of familiarity-driven RM for stimuli presented in the visual and olfactory domains. It has been suggested that abnormalities in conscious recollection result from a breakdown in frontal strategic memory processes involved in encoding and retrieval and executive functions linked to reality monitoring and decision making. We investigated three predictions arising from these proposals. Firstly, if conscious recollection abnormalities arise from a central impairment, then these abnormalities should not be domain specific. Secondly, if the deficits in conscious recollection arise from a breakdown in executive processes, deficiencies should be correlated with executive dysfunction. Finally, the conscious recollection deficiencies are likely to be more severe in schizophrenia, a condition associated with marked executive dysfunction relative to Major Depressive Disorder, Recurrent (MDDR), in which executive dysfunction is less marked. METHODS: The remember/know paradigm was used to investigate RM for voices in three groups: patients with schizophrenia (n = 14), patients with MDDR (n = 16), and normal controls (n = 16). Executive function was assessed using the Wisconsin Card Sorting Task. RESULTS: Patients with schizophrenia made significantly fewer remember responses than normal controls (p < 0.01), despite normal levels of discrimination and familiarity-driven auditory RM. Patients with MDDR did not differ significantly from either normal controls or patients with schizophrenia. Executive dysfunction was limited to the schizophrenia group and was not correlated with conscious recollection deficiencies. CONCLUSIONS: Patients with schizophrenia exhibit a deficit in conscious recollection for auditory RM of voices. These findings, when considered alongside remember/know data collected from the same set of patients for olfactory and visual RM, support proposals that abnormalities in conscious recollection stem from a breakdown in central rather than domain-specific processes.

Auditory Perception↗

Cortical and cognitive development in 4th, 8th and 12th grade students. The contribution of speed of processing and executive functioning to cognitive development.

This study investigated cortical/cognitive relations in 30 4th, 8th and 12th grade students. All students were administered the Figural Intersection Test, a measure of cognitive development, and performed, three times with different targets, an event-related potential (ERP) oddball/selective-attention task. Two independent factors emerged from the ERP task that predicted development--speed of processing (P300 latency to Block 1 targets) and maturation of executive functioning (a composite ERP variable calculated as the ratio of RT and P300 latency divided by the accuracy to Block 2 targets). These two variables loaded on orthogonal factors in a principal components analysis, and were the only variables included in a stepwise regression of physiological variables on cognitive development. Speed of processing is modulated by myelination and synaptogenesis, and executive functioning is modulated by maturation of the frontal system. These electrophysiological markers could index these cortical transformations underlying cognitive development.

Adolescent↗

Parkinson's disease and arithmetics: the role of executive functions.

Brain imaging studies as well as neuropsychological case studies suggest an important role for basal ganglia in arithmetic processing. Aim of this study was to assess possible numerical deficits in PD and functional relations between numerical and other cognitive deficits. Fifteen non-demented patients with early PD (stable responders treated by l-dopa) were compared to 28 healthy age and education matched controls. Both groups underwent a neuropsychological assessment focussing on numerical abilities (quantity processing, arithmetic fact retrieval, complex mental and written calculation, transcoding, arithmetic set-shifting, calculation span), working memory and executive functions. Patients with PD showed deficits in complex mental calculation and calculation span tasks. Results of this study suggest that impairments in working memory as well as in executive functions, such as inhibition of interference, lead to secondary deficits in numerical processing. The study contributes to better understanding the specific cognitive deficits in early PD and the neurocognitive architecture of arithmetic processing.

Aged↗

Updating information in verbal working memory and executive functioning.

50 older adults (M age=77.9 yr., SD=7.3; 35 women and 15 men) were tested using the updating working-memory task. They were also given the neuropsychological Wisconsin Card Sorting Test, assumed to evaluate executive functioning and the frontal cortex. A factor analysis with age, education, and verbal ability partialled out was computed on the updating task outcomes and resulted in a two-factor solution, indicating that this task requires two independent processes, interpreted as reflecting a storage component and an updating component. Partial correlations with age, education, and verbal ability partialled out indicated that Wisconsin Card Sorting Test measures were significantly associated with the factor supposed to reflect the updating process. Such results appeared consistent with the model of working memory with a central executive system involved in the updating process and related to the executive-frontal functioning, and a phonological loop system involved in the storage of verbal information and not linked to executive-frontal functions.

Aged↗

Neuropsychological deficits in tests of executive function in asymptomatic and symptomatic HIV-1 seropositive men.

There has been much debate about the exact nature and time of onset of the cognitive impairments associated with infection by the human immunodeficiency virus type 1 (HIV-1). Studies to date have not reached consistent conclusions. The present study comprised 22 asymptomatic and 18 symptomatic HIV-1 seropositive men, whose only risk factor for contraction of the virus was sexual intercourse, and 18 seronegative controls matched for age and IQ. Subjects were given computerized neuropsychological tests from the CANTAB battery, which assessed visuospatial memory, attention and executive function. Both the asymptomatic and the symptomatic HIV-1 seropositive subjects showed a selective pattern of deficits relative to the controls. In addition, the seropositive subjects were subtly but significantly impaired on tests of executive function but unimpaired on certain tests of visual memory. This finding supports an hypothesis that frontostriatal dysfunction occurs in HIV-1 infected individuals prior even to the expression of clinical symptoms.

Adult↗

Semantic memory and frontal executive function during transient global amnesia.

To assess semantic memory and frontal executive function, two patients underwent neuropsychological testing during transient global amnesia (TGA) and after an interval of 6-8 weeks. In spite of a profound deficit in anterograde verbal and non-verbal memory, semantic memory was normal, as judged by category fluency measures, picture naming, and picture-word and picture-picture matching, and reading ability was normal. Similarly, there were no deficits on a number of tests known to be sensitive to frontal executive dysfunction. A hexamethylpropyleneamine-oxime (HMPAO) single photon emission CT (SPECT) scan, obtained on one patient 24 hours post-TGA, showed focal left temporal lobe hypoperfusion which had resolved three months later. The observed dissociation between episodic and semantic memory is discussed in the light of contemporary cognitive theories of memory organisation.

Aged↗

Catechol-O-methyltransferase (COMT) Val108/158 Met polymorphism does not modulate executive function in children with ADHD.

BACKGROUND: An association has been observed between the catechol-O-methyltransferase (COMT) gene, the predominant means of catecholamine catabolism within the prefrontal cortex (PFC), and neuropsychological task performance in healthy and schizophrenic adults. Since several of the cognitive functions typically deficient in children with Attention Deficit Hyperactivity Disorder (ADHD) are mediated by prefrontal dopamine (DA) mechanisms, we investigated the relationship between a functional polymorphism of the COMT gene and neuropsychological task performance in these children. METHODS: The Val108/158 Met polymorphism of the COMT gene was genotyped in 118 children with ADHD (DSM-IV). The Wisconsin Card Sorting Test (WCST), Tower of London (TOL), and Self-Ordered Pointing Task (SOPT) were employed to evaluate executive functions. Neuropsychological task performance was compared across genotype groups using analysis of variance. RESULTS: ADHD children with the Val/Val, Val/Met and Met/Met genotypes were similar with regard to demographic and clinical characteristics. No genotype effects were observed for WCST standardized perseverative error scores [F2,97 = 0.67; p > 0.05], TOL standardized scores [F2,99 = 0.97; p > 0.05], and SOPT error scores [F2,108 = 0.62; p > 0.05]. CONCLUSIONS: Contrary to the observed association between WCST performance and the Val108/158 Met polymorphism of the COMT gene in both healthy and schizophrenic adults, this polymorphism does not appear to modulate executive functions in children with ADHD.

Amino Acid Substitution↗

Experience with V-STORE: considerations on presence in virtual environments for effective neuropsychological rehabilitation of executive functions.

The paper discusses the use of immersive virtual reality systems for the cognitive rehabilitation of dysexecutive syndrome, usually caused by prefrontal brain injuries. With respect to classical P&P and flat-screen computer rehabilitative tools, IVR systems might prove capable of evoking a more intense and compelling sense of presence, thanks to the highly naturalistic subject-environment interaction allowed. Within a constructivist framework applied to holistic rehabilitation, we suggest that this difference might enhance the ecological validity of cognitive training, partly overcoming the implicit limits of a lab setting, which seem to affect non-immersive procedures especially when applied to dysexecutive symptoms. We tested presence in a pilot study applied to a new VR-based rehabilitation tool for executive functions, V-Store; it allows patients to explore a virtual environment where they solve six series of tasks, ordered for complexity and designed to stimulate executive functions, programming, categorical abstraction, short-term memory and attention. We compared sense of presence experienced by unskilled normal subjects, randomly assigned to immersive or non-immersive (flat screen) sessions of V-Store, through four different indexes: self-report questionnaire, psychophysiological (GSR, skin conductance), neuropsychological (incidental recall memory test related to auditory information coming from the "real" environment) and count of breaks in presence (BIPs). Preliminary results show in the immersive group a significantly higher GSR response during tasks; neuropsychological data (fewer recalled elements from "reality") and less BIPs only show a congruent but yet non-significant advantage for the immersive condition; no differences were evident from the self-report questionnaire. A larger experimental group is currently under examination to evaluate significance of these data, which also might prove interesting with respect to the question of objective-subjective measures of presence.

Cognition Disorders↗

Deficits of memory, executive functioning and attention following infarction in the thalamus; a study of 22 cases with localised lesions.

The thalamus plays a crucial role in memory, executive functioning and attention. It remains, however, unclear whether thalamic structures have specific roles in each of these functions. We tested 22 cases of thalamic infarction, proven with MR imaging, using experimental and established neuropsychological tests. We performed a lesion-overlap study in standardised stereotactic space of patients sharing a certain deficit, corrected for the lesion distribution of patients without such deficits and determined the regions of interest using an atlas of the human thalamus. We checked for additional, non-thalamic, damage and for deficient comprehension and perception that would preclude interpretation of the results. Non-thalamic damage such as white matter lesions, hippocampal atrophy, sulcal widening and infarctions occur significantly more often in patients aged over 60. The patients with additional damage overlapped to a major degree with those who showed loss of orientation, or lack of comprehension of the test requirements. In the 10 patients judged 'clean', we observed a deficit of episodic long-term memory with relative sparing of intellectual capacities and short-term memory when the mammillo-thalamic tract was damaged. Lesions including the medial dorsal nucleus, midline nuclei and/or intralaminar nuclei accompany executive dysfunctioning. Reduced simple processing speed and attention are associated with age, but not with a particular structure in the thalamus. Complex attention deficits follow damage to the intralaminar nuclei.We conclude that the analysis of structure-function relationships must take into account extra-structure damage which may explain cognitive deficits. Separate thalamic structures are involved in memory, executive functioning and attention.

Adult↗

The role of dichotic listening performance and tasks of executive functions in reading impairment: a discriminant function analysis.

This study focused on the role of dichotic listening performance for the identification of reading impaired subtypes. Dichotic listening (DL), using verbal stimuli, has shown to be a valid measure of language lateralization. Usually, lateralization is estimated from the proportion of right ear over left ear accuracy during a free recall test procedure. However, it has been suggested that a more accurate estimate of laterality can be obtained by using a directed attention procedure. A sample of 43 reading disabled children of whom 18 showed signs of impaired language comprehension skills and 25 without language comprehension impairments, were compared to 20 age, and gender, matched controls on dichotic listening performance in both an unbiased free recall task and in a directed attention task using consonant-vowel syllables as dichotic stimuli. A laterality index was calculated for left and right ear stimuli reported during both the free recall condition and the attended ear-scores for the two directed attention conditions. Although both DL procedures yielded significant group differences, with a lower laterality score for the reading disabled compared to the controls, there was no main effect of DL-procedure or group x procedure interaction. Taken alone, DL performance could correctly classify 42% of the reading impaired samples, but together with other measures of executive functions, discriminant function analyses yielded 90.74% accuracy in classifying reading impaired children. The result indicates that DL together with tests of executive functions are valuable tools for assessment of reading impaired subjects.

Child↗

Neuropsychology of schizophrenia according to Kraepelin: disorders of volition and executive functioning.

Emil Kraepelin was the first to identify schizophrenia as a distinct disease in 1896. The purpose of this paper is to rediscover and reexamine the neuropsychology of schizophrenia according to Kraepelin. Kraepelin thought that the "dementia" of dementia praecox was primarily a disorder of volition, rather than one of intellect. "Volition" or "will" referred to the ability to make conscious decisions and to carry them out. By quoting relevant passages in his classic textbook, Dementia Praecox and Paraphrenia, the case is made that Kraepelin's detailed description of volitional deficits in patients with dementia praecox clearly documents impairments in executive functioning in schizophrenia patients during the preneuroleptic era. To a large extent, these deficits may be responsible for the "dementia" of dementia praecox and the "chronicity" of chronic schizophrenia. If this hypothesis is correct, the long-range prognosis of patients with schizophrenia may be considerably improved by treatment programs designed to facilitate executive functioning.

Affect↗

[Executive function disorders].

AIM: To review the development, anatomy and physiology of executive functions (EF) in normal and pathological conditions. DEVELOPMENT: EF consist of several internal mental process design to solve mental and environmental complex problems in an efficient and acceptable way to the person and the society. EF include inhibition of behavior and irrelevant information, nonverbal working memory, verbal working memory, self-regulation of affect, motivation and arousal, planning, decision making, self monitoring of the entire solving problem process and self evaluation of the results of the action taken. The anatomical substrate is at the prefrontal lobe cortex and its afferent and efferent structures. Neurotransmitters involved in activation of neurons at the prefrontal cortex are dopamine and norepinephrine and in less degree acetylcholine and serotonine. CONCLUSIONS: Disorders of one or more of the EF in children and adolescents are found in attention deficit/hyperactivity disorder, Tourette syndrome, bipolar disease, depression, obsessive-compulsive disorders, autism and traumatic brain injury.

Adolescent↗

Are endophenotypes based on measures of executive functions useful for molecular genetic studies of ADHD?

BACKGROUND: Behavioral genetic studies provide strong evidence that attention-deficit/hyperactivity disorder (ADHD) has a substantial genetic component. Yet, due to the complexity of the ADHD phenotype, questions remain as to the specific genes that contribute to this condition as well as the pathways from genes to behavior. Endophenotypes, or phenotypes that are more closely linked to the neurobiological substrate of a disorder, offer the potential to address these two issues simultaneously (Freedman, Adler, & Leonard, 1999). Thus far, potential endophenotypes for ADHD have not been systematically studied. METHOD: The current paper reviews evidence supporting the use of deficits on neurocognitive measures of executive functions for this purpose. RESULTS: Such deficits are a correlate of ADHD and show preliminary evidence of heritability and association with relevant candidate genes. Nonetheless, studies that have assessed the familial and genetic overlap of neurocognitive impairments with ADHD have yielded inconsistent results. CONCLUSIONS: In order for executive function deficits to be used as an endophenotype for ADHD, we recommend greater attention to the neurocognitive heterogeneity of this disorder and to the precision of measurement of the neuropsychological tests employed. We also discuss empirical strategies that may be necessary to allow such research to progress prior to full resolution of the pathophysiological basis of ADHD.

Attention Deficit Disorder with Hyperactivity↗

Executive function in multiple sclerosis. The role of frontal lobe pathology.

Deficits in executive function and the relationship to frontal lesion load as detected on MRI were investigated in 42 multiple sclerosis patients. A battery of neuropsychological test examining executive skills including computerized tests of planning and spatial working memory was administered to all subjects. Performance on these tests was impaired in the patient group when compared with a group of matched controls, but not all executive skills were affected to the same extent. Although a number of executive test scores correlated with the severity of frontal lesion load, it was difficult to disentangle the specific contribution of frontal lobe pathology to the impairment on executive tasks. This study highlights the difficulties in attempting to attribute specific cognitive abnormalities to focal brain pathology in the presence of widespread disease such as in multiple sclerosis.

Adolescent↗

High-potency marijuana impairs executive function and inhibitory motor control.

Human performance studies have usually relied on low-potency marijuana (4% THC) for determining THC-induced impairment. The present study was designed to assess the effects of high-potency marijuana (13% THC) on human performance. In all, 20 recreational users of marijuana participated in a double-blind, placebo controlled, three way cross-over study. The treatments consisted of single doses of 0, 250, and 500 microg/kg THC. Performance tests were conducted at regular intervals between 15 min and 6 h postsmoking and included measures of motor control (Critical tracking task), executive function (Tower of London) motor impulsivity (Stop signal task), and risk taking (Iowa gambling task). THC significantly impaired performance in the Critical tracking task and decreased the number of correct decisions in the Tower of London task. In addition, THC significantly increased stop reaction time and the proportions of commission and omission errors in the Stop signal task. THC-induced impairments lasted up to 6 h postsmoking as indicated by the absence of a THC x Time after smoking interaction. Effect sizes for performance impairments produced by THC 250 microg/kg were relatively low but generally increased by a factor of two in case of THC 500 microg/kg. These data suggest that high potency marijuana consistently impairs executive function and motor control. Use of higher doses of THC in controlled studies may offer a reliable indication of THC induced impairment as compared to lower doses of THC that have traditionally been used in performance studies.

Adult↗

Executive function and theory of mind performance of boys with fragile-X syndrome.

Fragile-X syndrome is the most common genetically inherited cause of intellectual disability. People with this syndrome typically show a behavioural profile of abnormal social interactions which are similar in some ways to those seen in people with autism. The present study investigated whether cognitive processes which have been hypothesized to underlie social abnormalities associated with autism are also impaired in boys with fragile-X syndrome without autistic spectrum disorders. Eight boys with fragile-X syndrome and eight with intellectual disability of unknown aetiology, matched on receptive verbal ability, age and with no diagnosis of autism, were tested on a battery of theory of mind and executive function tasks. Significantly more boys with fragile-X syndrome failed the simplest theory of mind task. However, this could be attributed to overall level of ability rather than group membership. No differences were found between the groups on any other measures used. A proportion of both groups failed first- and second-order false belief tasks. The performance of both groups on the executive function measure was at the floor of the test. At low levels of overall ability, the performance of boys with fragile-X syndrome and boys with intellectual disability of unknown aetiology may be more similar than they are different The implication of this result for clinical interventions is discussed.

Adolescent↗

Striatal contribution to cognition: working memory and executive function in Parkinson's disease before and after unilateral posteroventral pallidotomy.

The basal ganglia are intimately connected to the frontal cortex via five fronto-striatal circuits. While the role of the frontal cortex in cognition has been extensively studied, the contribution of the basal ganglia to cognition has remained less clear. In Parkinson's disease, posteroventral pallidotomy (PVP) involves surgical lesioning of the internal section of the globus pallidus (GPi, the final output pathway from the basal ganglia) to relieve the motor symptoms of the disorder. PVP in Parkinson's disease provides a unique opportunity to investigate the impact of disruption of striatal outflow to the frontal cortex on cognition. We assessed executive function and working memory after withdrawal of medication in 13 patients with Parkinson's disease before and 3 months after unilateral PVP compared to 12 age- and IQ-matched normals assessed twice with an interval of 3 months. The tests used were: Wisconsin Card Sorting (WCST), Self-Ordered Random Number Sequences, Missing Digit Test, Paced Visual Serial Addition Test (PVSAT), and Visual Conditional Associative Learning Test (VCALT). After PVP, the patients performed significantly better on the Self-Ordered Random Number Sequences and the WCST, an improvement that was also observed in the normals across the two assessment and is therefore likely to reflect practice effects. Relative to the normals, the patients showed significant differential change following PVP on the Missing Digit Test and PVSAT, on which they performed worse after compared to before surgery, while the controls performed better on the second assessment. For the patients, performance on the VCALT also indicated deterioration after PVP, but the changes approached significance. The side of PVP had no effect on the results. The pattern of change observed 3 months after PVP was maintained at 15-month follow-up. The results suggest that striatal outflow to the frontal cortex may be essential for those aspects of executive function that showed deterioration after PVP.

Adult↗

Working memory and executive functions in transient global amnesia.

Transient global amnesia (TGA) is usually considered to produce a profound impairment of long-term episodic memory, while at the same time sparing working memory. However, this neuropsychological dissociation has rarely been examined in detail. While a few studies have assessed some components of working memory in TGA, the results that have been obtained are far from conclusive. To clarify this issue, we carried out a comprehensive investigation of working memory in 10 patients during a TGA attack. In the first study, we report the results from three patients examined with a battery of neuropsychological tests designed to assess each of the three subcomponents of Baddeley's model of working memory. In a second study, seven different patients underwent neuropsychological investigations that focused specifically on the central executive system, using a protocol derived from a study by Miyake and colleagues. Our findings showed that subcomponents of working memory, such as the phonological loop and visuo-spatial sketch pad, were spared in TGA patients. Specific executive functions that entailed inhibitory control, dual task performance, updating and shifting mechanisms were also found to be normal. However, we found significantly impaired performance for the Brown-Peterson test, and that TGA patients were significantly impaired in the recollection of their episodic memories. They also made reduced numbers of 'remember' compared with 'know' judgments in the episodic memory test several days after TGA. On the basis of our findings, it would appear that the episodic memory deficit during TGA is not related to elementary aspects of executive functioning. Our data also highlight the nature of the cognitive mechanisms involved in the Brown-Peterson task, which may well depend on long-term memory (such as the process of semantic encoding). Lastly, the selective deficit in recollective episodic memories observed in TGA may be principally related to medial temporal lobe abnormalities that have been reported in this syndrome.

Aged↗