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Cognitive deficits in parents from multiple-incidence autism families.

This study compares parents of two autistic children with parents of a Down syndrome (DS) proband, on tests of intelligence, reading and spelling, and executive function. Autism parents performed significantly worse than DS parents on performance IQ, a test of executive function, and some reading measures (e.g. passage comprehension and rapid automatized naming). These results suggest that cognitive deficits may be an expression of the underlying genetic liability for autism and that these characteristics may contribute to a more broadly defined autism phenotype.

Adolescent↗

Effects of galantamine on working memory and global functioning in patients with mild cognitive impairment: a double-blind placebo-controlled study.

Mild cognitive impairment (MCI) causes memory impairment and executive function deficits in those with the condition. There is also some evidence that MCI patients are impaired in their daily functioning. Cholinesterase inhibitors have been widely used for patients with Alzheimer's disease (AD), with evidence of improving cognitive function. There is currently no established treatment for MCI, and cholinesterase inhibitors are beginning to be studied in these patients. Galantamine is a cholinesterase inhibitor that also has nicotinic receptor-modulating properties that has been successful in improving AD patients. This study examined the effects of galantamine in patients with MCI in areas of memory, executive functioning, and global functioning. There was a significant improvement in scores on the Functional Activities Questionnaire, which is a measure of global functioning. There were also improvements in the galantamine group on two of six measures in the Cambridge Automated Neuropsychiatric Test Assessment Battery and in immediate free recall on the California Verbal Learning Test.

Activities of Daily Living↗

Differential effect of a dopaminergic agonist on prefrontal function in traumatic brain injury patients.

We examined the effects of low-dose bromocriptine, a D2 dopamine receptor agonist, on processes thought to be subserved by the prefrontal cortex, including working memory and executive function, in individuals with traumatic brain injury. A group of 24 subjects was tested using a double-blind, placebo-controlled crossover trial, counterbalanced for order. Bromocriptine was found to improve performance on some tasks thought to be subserved by prefrontal function, but not others. Specifically, there was improvement in performance on clinical measures of executive function and in dual-task performance, but not measures that tap the ability to maintain information in working memory without significant executive demands. Also, on control tasks not thought to be dependent on the prefrontal cortex, no improvement on bromocriptine was noted. These results demonstrate a selective effect of bromocriptine on cognitive processes which involve executive control, and provide a foundation for potential therapies for patients with prefrontal damage causing dysexecutive syndromes.

Adult↗

Differential performance on tasks of affective processing and decision-making in patients with Panic Disorder and Panic Disorder with comorbid Major Depressive Disorder.

BACKGROUND: Neuropsychological studies have provided evidence for deficits in psychiatric disorders, such as schizophrenia and mood disorders. However, neuropsychological function in Panic Disorder (PD) or PD with a comorbid diagnosis of Major Depressive Disorder (MDD) has not been comprehensively studied. The present study investigated neuropsychological functioning in patients with PD and PD + MDD by focusing on tasks that assess attention, psychomotor speed, executive function, decision-making, and affective processing. METHODS: Twenty-two unmedicated patients with PD, eleven of whom had a secondary diagnosis of MDD, were compared to twenty-two healthy controls, matched for gender, age, and intelligence on tasks of attention, memory, psychomotor speed, executive function, decision-making, and affective processing from the Cambridge Neuropsychological Test Automated Battery (CANTAB), Cambridge Gamble Task, and Affective Go/No-go Task. RESULTS: Relative to matched healthy controls, patients with PD + MDD displayed an attentional bias toward negatively-valenced verbal stimuli (Affective Go/No-go Task) and longer decision-making latencies (Cambridge Gamble Task). Furthermore, the PD + MDD group committed more errors on a task of memory and visual discrimination compared to their controls. In contrast, no group differences were found for PD patients relative to matched control subjects. LIMITATIONS: The sample size was limited, however, all patients were drug-free at the time of testing. CONCLUSIONS: The PD + MDD patients demonstrated deficits on a task involving visual discrimination and working memory, and an attentional bias towards negatively-valenced stimuli. In addition, patients with comorbid depression provided qualitatively different responses in the areas of affective and decision-making processes.

Adult↗

Susceptibility of spatial and verbal working memory to demands of the central executive.

We used a dual-task paradigm to examine the degree to which domain-specific spatial and verbal subsystems depend on the domain-general central executive. Forty participants were asked to retain spatial or verbal information while performing a concurrent secondary task related to simple arithmetic. The secondary tasks consisted of three cognitive processes: single-digit addition, a digit-carrying operation, and digit reading. The single-digit addition and carry operation include central executive functioning, while digit reading relies solely on the phonological loop. The single-digit addition caused a performance decrement on the spatial working memory task, while the digit reading impaired performance on the verbal working memory task. The carry operation interfered with recall accuracy on both working memory tasks. The spatial working memory task was significantly correlated with the verbal working memory task only when the secondary task was more demanding on the central executive. Our results suggest that spatial working memory rather than verbal working memory is susceptible to failure of central executive functioning and that the central executive plays an important role in regulating the cognitive demands of different domains.

Journal Article↗

Early and late neurodevelopmental disturbances in schizophrenia and their functional consequences.

OBJECTIVE: The evidence from structural imaging studies supports the notion that schizophrenia arises from an early abnormality in brain development. In this paper we review the timing of structural changes in schizophrenia and argue that schizophrenia is a neuro-developmental disorder with limited progressive brain changes occurring during the evolution and early phase of psychosis. METHOD: The available cross-sectional and longitudinal studies are reviewed, along with data from our own research. RESULTS: The current literature, including our own data, suggests that structural brain changes are apparent premorbidly, consistent with a neurodevelopmental lesion. These are prominent in frontal and cingulate regions, and appear related to premorbid neuropsychological deficits in executive function. However, there appear to be additional brain changes over the transition to illness and beyond. CONCLUSIONS: We propose first, that an early neurodevelopmental insult interacts with either normal or abnormal postpubertal brain maturation to produce further (late neurodevelopmental) brain structural and functional changes; and second, that the effect of such neurodevelopmental lesions will have different consequences for functions that normally develop early in life, such as memory, compared with functions developing later, such as executive functions. A model is presented suggesting that the structural and functional abnormalities in schizophrenia can be understood as a consequence of the neurodevelopmental stage at which brain changes occur.

Brain↗

Assessing olfaction in the neuropsychological exam: the relationship between odor identification and cognition in older adults.

The relationship between odor identification and cognition has not been previously well characterized. The neuroanatomy of the olfactory system and the frequent finding of olfactory dysfunction in neurodegenerative diseases suggest a likely relationship between odor identification and memory, language, and executive functioning, though previous studies have often failed to demonstrate the expected relationship. The current study examined this relationship in across a continuum of ability levels (N=100). Strongest correlations were found between odor identification and language, most aspects of memory, and a measure of general cognitive functioning. Significant but more modest correlations were seen between odor identification and attention, motor, visuospatial, and executive functions. A regression analysis revealed language as the only significant predictor of olfactory performance. These findings suggest that odor identification is most closely associated with other measures of temporo-limbic functioning. The implications of these findings, particularly in consideration of the assessment of older adults, are discussed.

Aged↗

Neuropsychological dysfunction, soft neurological signs and social disability in euthymic patients with bipolar disorder.

BACKGROUND: Neurocognitive deficits exist in euthymic patients with bipolar disorder, but relationships between symptoms, psychosocial and neurological factors remain uncertain. AIMS: To measure neurocognitive function in bipolar disorder and explore links to sub-syndromal mood symptoms, soft neurological signs and psychosocial impairment. METHOD: Attention, memory and executive function were tested in 37 euthymic patients with bipolar disorder and 37 controls. Psychosocial functioning, soft neurological signs and residual mood symptoms were assessed. RESULTS: Performances on tests reflecting executive function and verbal memory (but not attention) were significantly poorer in the bipolar disorder group. Sub-syndromal mood symptoms produced small cognitive effects, predominantly on verbal memory. Soft neurological signs, especially frontal signs, were marked; some patients showed marked social disability which correlated strongly with soft neurological signs but weakly with executive dysfunction, which was linked to illness episodes. CONCLUSIONS: Cognitive dysfunction, social dysfunction and soft signs occur in euthymic patients with bipolar disorder and may represent trait deficits.

Adult↗

Cognition in schizophrenia: impairments, determinants, and functional importance.

Recent findings support and add to earlier findings of cognitive dysfunction in schizophrenia. Deficits across neurocognitive domains such as attention, working memory, language skills, and executive functioning tend to be moderate, with the most pronounced deficits found in verbal learning and memory. All these neurocognitive domains are related to adaptive and social skills, with executive functions and verbal learning and memory showing more variance across more domains than other neuro-cognitive variables. Negative symptoms and neurocognitive domains, although correlated, are distinct and have differential pathways of change with treatment. General psychopathology symptoms, such as depression and anxiety, may become important treatment targets as strategies are developed for translating cognitive enhancement to real-world functional performance.

Antipsychotic Agents↗

The Maudsley Bipolar Disorder Project.

PURPOSE: The Maudsley Bipolar Disorder Project set out to investigate the cognitive and brain structural and functional characteristics of Bipolar Disorder I (BDI). METHODS: Participating patients were recruited while in remission from a secondary care setting and were matched to healthy volunteers in terms of age, gender, race, and years of education. All participants underwent extensive clinical and cognitive assessment. Brain structural and functional data also were obtained by using magnetic resonance imaging (MRI). RESULTS: Compared with controls, patients showed subtle widespread decrements, with executive function being more markedly impaired. Patients also showed volume decrements in the ventral prefrontal cortex (VPFC) bilaterally and the dorsal PFC (DPFC) on the left, whereas the volume of the amygdala was bilaterally enlarged. Patients showed subtle abnormalities in functional MRI in their DPFC, with marked decrements in activity in both the DPFC and VPFC in tasks that rely on the functional interaction of these brain regions. CONCLUSIONS: Our results suggest that BDI is associated with trait deficits in executive function and in the structure and function of the PFC.

Adult↗

Selective dendritic degeneration of medium spiny neurons in dementia with Lewy bodies.

Dementia with Lewy bodies (DLB) is the second most common form of dementia and shows more severely impaired performance on tests of executive functions compared to Alzheimer disease. Here the authors demonstrate selective spinodendritic degeneration of medium spiny neurons in regions of the caudate nucleus that subserve executive functions and propose that this may underlie, at least in part, the heightened executive dysfunction observed in patients with DLB.

Aged↗

Neuroimaging and electrophysiological studies of the effects of acute tryptophan depletion: a systematic review of the literature.

RATIONALE: There is a growing psychopharmacological literature on the use of Acute Tryptophan Depletion (ATD) for experimental modulation of the serotonergic system. To date, no systematic review has been undertaken assessing the neurophysiological effects following this acute central 5-HT manipulation. MATERIALS AND METHODS: A comprehensive MEDLINE, EMBASE, PsycINFO search was performed for reports on neural substrates of Acute Tryptophan Depletion in healthy individuals and in clinical population. RESULTS: Twenty-eight placebo-controlled studies were included in the review. Although tryptophan depletion reduced plasma serotonin levels in all studies, significant effects on mood were only observed in studies with recovered depressed patients. In functional neuroimaging studies ATD was consistently found to modulate cortical activity in prefrontal areas implicated in mnemonic and executive functions and in orbitofrontal, cingulate, and subcortical regions associated with emotional processing. Electrophysiological studies indicated that ATD has a significant effect on both "selective" and "involuntary" attention. CONCLUSIONS: The combination of ATD with modern brain imaging techniques allows the investigation of the neurophysiological effects of reduced 5-HT synthesis on global brain activity, executive functions, memory, attention, and affect.

Electroencephalography↗

Wayfinding in familiar and unfamiliar environments in a case of progressive topographical agnosia.

A 71-year-old right-handed man (F.G.) presents with prosopagnosia and with an inability to recognize famous and familiar buildings. Despite his deficit, F.G. obtained normal scores on neuropsychological tests of executive functions, language, praxis and primary visuoperceptual skills. Brain MRI showed atrophy predominantly in the right temporal lobe, particularly in the fusiform gyrus and the parahippocampal cortex. The present study investigated F.G.'s ability to orient himself in familiar and new environments. His wayfinding abilities in a familiar environment (i.e., his hometown) were preserved despite an inability to recognize familiar and famous buildings, monuments and landmarks in this environment. Wayfinding was achieved through a heavy reliance on written indications (e.g., names of restaurants and streets), preservation of a pre-existing cognitive map of this familiar environment, and normal executive functions necessary to plan the execution of a given trajectory. In an unfamiliar environment, F.G.'s topographical agnosia resulted in severe wayfinding difficulties and in the inability to build an adequate cognitive spatial representation. F.G.'s topographical agnosia results from a high-level visuoperceptual deficit, characterized by an inability to access a global configuration of complex visual stimuli such as familiar and famous monuments, and an over-reliance on the processing of local features.

Aged↗

Asperger's syndrome: evidence of an empirical distinction from high-functioning autism.

This study compared the neuropsychological profiles of individuals with high-functioning autism (HFA) and Asperger's syndrome (AS). In comparison with matched controls, both groups were impaired on executive function tests. Only the HFA group demonstrated deficits in theory of mind and verbal memory, performing more poorly than both controls and AS subjects. These results suggest that: (1) HFA and AS are empirically distinguishable on measures independent of diagnostic criteria, and (2) impairment on theory of mind measures is not universally found among individuals with autistic spectrum conditions. The primacy of executive function and theory of mind deficits to autism is discussed.

Autistic Disorder↗

Cognitive estimation in patients with probable Alzheimer's disease and alcoholic Korsakoff patients.

Cognitive estimation is an important function in daily living. In early studies it was proposed that estimation deficits are associated with frontal lobe damage and executive dysfunctions. In this study, we assessed Alzheimer patients and patients with alcoholic Korsakoff's syndrome with a newly developed cognitive estimation task. We compared their performance with respect to different dimensions of estimation ('size', 'weight', 'quantity', and 'time') and to various error types. Compared to healthy controls, both patient groups were strongly impaired in all tested estimation dimensions, with Alzheimer patients performing generally worse than Korsakoff patients, except for the dimension "time". Alzheimer as well as Korsakoff patients produced so-called 'bizarre errors' and errors in the choice of the correct unit of measurement. In both patient groups cognitive estimation correlated highly with general knowledge. The production of bizarre errors and unit errors correlated with general knowledge as well as with working memory and executive functions. Results support the main assumptions of a model of cognitive estimation, described in the discussion, that specific parts of the semantic memory system as well as executive functions, in form of a plausibility check of the generated answer, are involved in the process of cognitive estimation.

Aged↗

Mild myotonic dystrophy is associated with memory impairment in the context of normal general intelligence.

Previous investigations of cognitive function in myotonic dystrophy (DM) suggested that DM subjects have impairment of general intelligence and severe defects in executive function. These studies had to neglect patients with mild clinical disease, since they were generally performed before the availability of DNA testing for DM. We have investigated a group of milder DM cases (defined both by their degree of disability and CTG expansion size) and have not found any defect in general intelligence using the National Adult Reading Test, Standard Progressive Matrices, and Mini-Mental State examination. Three executive function tests were used. The cognitive estimates test and the Wisconsin Card Sorting Test showed tendencies towards impairment, which were of borderline significance, but the verbal fluency task was performed normally. However, in the face of normal general intelligence, mild DM subjects as a group show impairment of memory function. This suggests that memory function may be more sensitive to small CTG repeat expansions than general intelligence.

Adolescent↗

Virtual planning in patients with frontal lobe lesions.

The VIrtual Planning Test (VIP) was developed to investigate the planning and organisational abilities of 25 patients with frontal lobe neurosurgical lesions, comparing their performance with 25 matched control subjects. The task, presented in the form of a board game, simulates planning and execution of a set of target activities that have to take place over a four day period, involving those that are either preparatory for a fictional "trip" abroad, or those that relate to the subject's current environment (context). The frontal lobe patients were impaired overall, tending to select inappropriate activities associated with their current context and showing greater impairment on subtasks requiring only one, rather than two, preparatory acts. The findings are discussed in terms of the validity of the VIP test in identifying executive functioning impairment and the degree to which the pattern of deficits are consistent with neuropsychological models of executive function.

Adult↗

The neuropsychiatry of carbon monoxide poisoning in attempted suicide: a prospective controlled study.

OBJECTIVE: There are few prospective comprehensive controlled studies of the neuropsychiatric outcome in people who attempt suicide with carbon monoxide (CO). The present study aimed to evaluate this. METHODS: A consecutive series of 41 adults (81% men) with CO exposure presenting over 3 years, and 20 matched controls, were evaluated with instruments to assess orientation, attention, concentration, speed of information processing, verbal memory, premorbid intellect, executive function (working memory, verbal fluency and set-switching), mood disorder, psychotic disorder, alcohol dependence and obsessive-compulsive disorder, levels of depression, hopelessness, suicide intent, anxiety, neurobehavioural function and social and interpersonal functioning. At 2 months follow-up, the neuropsychological battery was extended to include further tests of executive function (including problem-solving) and memory (including visual memory), RESULTS: At initial assessment, control subjects showed similar levels of cognitive impairment as CO-exposed subjects (except in the case of four CO subjects with very severe impairment), but were more depressed. At 2-months follow-up, the trends were generally towards improvement in all subjects, with no between-group differences. CONCLUSIONS: Indirect effects on cognitive state may be at least as great as direct CO neurotoxicity in suicide attempters. The study did not support CO exposure exacerbating mood disorder in this sample.

Adult↗