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Disorders in executive control functions among aphasic and other brain-damaged patients.

Four experimental procedures for assessing disorders of executive control (Nonverbal Continuous Performance, Graphic Pattern Generation, Sequence Generation Test, and Tower of Hanoi) were administered to 22 left-brain-damaged aphasic patients, 19 right-brain-damaged nonaphasic patients, and 49 healthy controls. Aphasic patients with frontal-lobe lesions were significantly more impaired on these tasks than aphasics with retrorolandic or mixed lesions in the left hemisphere. Patients with right-hemisphere lesions, especially those with frontal-lobe lesions, showed even greater impairments on these visual/spatial tasks. The results suggest that aphasics' impairments in executive control are independent of their linguistic and visuospatial deficits and are specific to lesions in left frontal and prefrontal regions. The clinical utility of the experimental procedures is discussed.

Adult

Frontal lobe lesions, diffuse damage, and neuropsychological functioning in traumatic brain-injured patients.

This study quantified lesion volume in relation to damage location and executive functioning in traumatic brain-injured (TBI) patients. Magnetic resonance (MR) scans of 68 TBI patients were analyzed by taking volumetric measures of lesion sites. Patients were grouped according to the presence/absence of frontal lobe lesions. Measures of frontal lesion volume were studied as predictors for outcome on designated tests of executive functioning (Halstead Category Test and Wisconsin Card Sorting Test). Results showed no significant differences in level of deficit between groups. In addition, no significant differences were found between groups on other tests of neuropsychological functioning (Trail Making Test, Parts A and B, and Wechsler Adult Intelligence Scale-Revised). These results suggest that tests that are traditionally used to detect "frontal lobe" damage may not be adequate for distinguishing specific frontal lobe dysfunction, and do not add anything unique about frontal lobe integrity and neuropsychological functioning in TBI patients.

Brain Damage, Chronic

Neuropsychological function in mild hyperphenylalaninemia.

Whether specific cognitive deficits related to frontal-lobe dysfunction that have been reported in individuals with phenylketonuria (PKU) are also characteristic of mild hyperphenylalaninemia (MHP) was investigated. Tests of executive function and control tasks not assessing executive function were administered to a group of individuals with MHP and a group without MHP, similar in age, gender, and IQ. Tests of academic skills and behavior-rating questionnaires were also administered to the group with MHP. No group differences were found for any measure, suggesting that the mild elevations of phenylalanine in individuals with MHP are not sufficient to produce behavioral and cognitive impairments characteristic of PKU.

Adolescent

[Neuropsychological deficits in depressive disorders].

Neuropsychological deficits are considered a significant feature of depression both for their differential value in the diagnostics and the underlying pathophysiology of depressive disorders. The studies reviewed in the present paper predominantly focus on memory disorders as well as frontal-lobe associated dysfunctions such as deficits of attentional performance and executive functions. Despite heterogeneous results in the literature, there is emerging evidence that executive functions and anterograde memory performance are those domains predominantly affected in depressive disorders. The fact that not all depressive patients display neuropsychological deficits rather indicates a dominant role of moderating variables. We discuss the following variables possibly intervening with type and degree of neuropsychological dysfunction: [1] severity and remission of depressive disorders, [2] age of patients and age at the first manifestation of a depressive disorder, [3] psychological factors such as motivation and coping with failure, [4] type and efficacy of antidepressive drug treatment, [5] duration of the stay as inpatients, [6] number of depressive episodes, and [7] gender. Furthermore, we discuss the theory of a dysfunction of fronto-striatal circuits as an underlying mechanism of depressive disorders. The majority of neuropsychological findings seem to support this theory.

Attention

Neuropsychological features of early Alzheimer's disease: preclinical and clinical stages.

In the preclinical stage of Alzheimer's disease (AD), studies of asymptomatic mutation carriers have identified impairments in episodic memory. Other cognitive functions show no or slight impairment suggesting that preclinical AD is a unifunctional cognitive syndrome; the brain is affected selectively and predominantly in the medial temporal structures. In the early clinical stage, deficits occur in episodic memory, verbal abilities, visuospatial functions, attention, and executive functions. AD becomes a multifunctional cognitive syndrome and the brain's association cortices are affected. Nevertheless, sensory-motor performance and procedural memory seem to be intact and only slight impairment may be seen in primary memory. In advanced AD, cognitive dysfunction including deficits is global in primary memory, although sensory-motor performance may be well preserved. The brain's association cortices are severely affected. The sequence of cognitive decline; from unifunctional to global deficits, conforms to the three-stage development of neurofibrillary tangles described by Braak and Braak.

Alzheimer Disease

Are there sex differences in neuropsychological functions among patients with schizophrenia?

OBJECTIVE: Studies of sex differences in neuropsychological performance in schizophrenia report inconsistent results, due in part to methodological artifacts. The study presented here was specifically designed to examine sex differences in neuropsychological performance. It was hypothesized that schizophrenic women would exhibit fewer neuropsychological deficits than schizophrenic men and that their performance would be more similar to that of normal women than schizophrenic men's performance would be to that of normal men. METHOD: Thirty-one outpatients with DSM-III-R-defined schizophrenia were systematically sampled from an extensive service network serving a large urban catchment area for seriously mentally ill persons. Twenty-seven normal comparison subjects were matched within sex on the basis of age, parental socioeconomic status, ethnicity, and handedness. An extensive neuropsychological test battery was administered, and multivariate analysis of variance was used to test for the effects of sex and group and sex-by-group interactions. RESULTS: Male patients were significantly impaired across all functions in comparison with normal male subjects and on tests of attention, verbal memory, and executive functions in comparison with female patients. Female patients performed significantly worse than female normal comparison subjects only on tests of attention, executive functions, visual memory, and motor functions. CONCLUSIONS: The findings suggest that women with schizophrenia may be less vulnerable to particular cognitive deficits, especially those involving verbal processing, than schizophrenic men.

Adult

Prenatal exposure to marihuana and tobacco during infancy, early and middle childhood: effects and an attempt at synthesis.

Both marihuana and cigarettes appear implicated, in a differential fashion, in the neurobehaviour of infants and children born to women who used these substances during pregnancy. In a low-risk upper middle class sample, marihuana use was associated, in the newborn, with mild withdrawal symptoms and some autonomic disruption of nervous system state regulation. However, between 6 months and 3 years of age no behavioural consequences of marihuana exposure (once confounding factors were controlled) were noted. At four years of age, although global tests of intelligence did not differentiate exposed from non-marihuana exposed children, verbal ability and memory were associated with in utero marihuana exposure. At five and six years of age these general areas were also noted to be associated with maternal cannabis use as was sustained attention. These areas of neurobehavior that appear affected by marihuana exposure during fetal development are ones that are consistent with the cognitive construct of 'executive functioning' which is thought to be a marker of prefrontal lobe functioning. Consistent with the observations derived from these children is that prefrontal functioning may not be apparent until approximately four years of age and that executive functioning is disassociated from measures of global intelligence. Exposure to cigarettes during pregnancy appears to be associated with neurobehavioural deficits in the auditory domain. In the newborn this is manifested by decreased responsivity to sound and altered auditory habituation. Between the ages of one and 11 years the performance on auditory related tasks (verbal memory, language, auditory processing) were consistently the domains that differentiated the cigarette exposed from the non exposed children. The possible role of the cholinergic mediated efferent auditory system is discussed. Also associated with in utero exposure to cigarettes were general cognitive performance and parental reports and objectively derived measures of impulsivity. The striking degree of consistency over the years lends strength to the interpretation that the observations in childhood have, at least as their partial etiology, the prenatal exposure to cigarettes. However, in interpreting the evidence presented it must be recognized that the alterations in the child's behaviour may well affect the parenting behaviour. This potential transactional interaction must remain an integral part of drawing conclusions about both marihuana and cigarette's effects.

Behavior

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

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

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

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

Cognitive deficits in patients with small cell lung cancer before and after chemotherapy.

We conducted a prospective study of cognitive function in patients with small cell lung cancer (SCLC). A previous study had shown SCLC patients to have deficits in memory, frontal lobe executive functioning, and motor skills before they received prophylactic cranial irradiation (PCI). This study was performed to determine whether these deficits were related to chemoradiation treatment. We evaluated two groups of patients: one newly diagnosed and untreated, the other post-chemoradiation and before PCI. Strict eligibility criteria were used to minimize any preexisting factors that might influence cognitive functioning. Results showed that patients with SCLC have cognitive deficits before receiving chemoradiation, specifically on tests of verbal memory, frontal lobe executive functions, and motor coordination. There was no difference between the treated and untreated patients on any test. Etiologic considerations currently under study include paraneoplastic phenomena.

Adolescent

Behavioural changes after closed head injury. A neuropsychological issue.

The long-term behavioural consequences of moderate to severe closed head injury (CHI) have been examined within a neuropsychological framework. It is argued that neuropsychological assessment must be considered if the behavioural sequelae of a brain injury are to be fully appreciated and assessment and rehabilitation modules appropriately formulated. Functioning of the frontal lobes is emphasised because this is the area most at risk when a head injury occurs. The meaning of 'executive functions' is examined, and the behavioural and rehabilitation implications of an impaired 'executor' are discussed. It is demonstrated that traditional individual and family-based psychotherapeutic techniques are inappropriate for people with impaired executive functions.

Behavior

The effects of chronic administration of hydrocortisone on cognitive function in normal male volunteers.

RATIONALE: Corticosteroids are elevated in certain neuropsychiatric disorders and this may contribute to the neuropsychological impairments reported in these disorders. OBJECTIVE: To examine the effects of hydrocortisone on learning, memory and executive function. METHODS: Hydrocortisone 20 mg was administered twice daily for 10 days to normal male volunteers in a randomized, placebo control, crossover, within-subject design. Learning, memory and executive function were measured using selected subtests from the Cambridge Neuropsychological Test Automated Battery. RESULTS: Hydrocortisone caused impairments of visuo-spatial memory. These included increased within search errors and impaired use of strategies on the spatial working memory subtest. In addition, administration of hydrocortisone was associated with more errors in the paired associate learning subtest, although no effect was found on the Tower of London. Hydrocortisone speeded response latencies in certain tests (pattern and spatial recognition memory). CONCLUSION: These results indicate that chronic administration of hydrocortisone leads to deficits in certain tests of cognitive function sensitive to frontal lobe dysfunction and may contribute to the cognitive impairment reported in certain neuropsychiatric disorders.

Adult

Neuropsychological changes in a prospectively followed cohort of homosexual and bisexual men with and without HIV infection.

We evaluated neuropsychological test performance of 168 homosexual and bisexual men with and without human immunodeficiency virus (HIV) infection (113 HIV+ subjects and 55 HIV- controls) over 4.5 years of semiannual follow-up. Analyses of the longitudinal data were performed by applying generalized estimating equations (GEEs) to regression analyses with repeated measures. Compared with the HIV- men, the HIV+ subjects performed more poorly on memory testing. Performance on all tests tended to improve over time, but this improvement was attenuated or eliminated in the HIV+ group for tests of language and attention. Within the HIV+ subjects, improvement over time in tests of memory, executive function, language, and attention was attenuated or eliminated in patients with lower CD4 levels; more advanced HIV disease was associated with poorer memory and executive function and with attenuated or reduced learning effects for memory, motor speed, and language tests. Clinically significant neurologic findings were associated with worse memory and orientation and with attenuated or reversed learning effects for memory, language, and attention tests. There were 33 deaths in the HIV+ group. In the men who died, there was more rapid decline in executive, language, and attentional test performance. These observations remained significant after controlling for HIV disease severity. We conclude that HIV infecting the CNS results in progressive cognitive change that is closely associated with neurologic findings. In addition, our findings suggest a relation between more rapid cognitive progression and death.

Adult

Is the phonological loop responsible for intelligence-related differences in forward digit span?

Children with mild mental retardation were compared with CA-matched and verbal-age-matched children without mental retardation on a forward digit span task. Forward digit span is typically used as a measure of the phonological loop (Baddeley, 1986). We hypothesized that intelligence-related differences in forward digit span are largely due to central executive functioning rather than phonological loop functioning. Results showed that the highly significant group difference in forward digit span was reduced to nonsignificance when a measure of central executive functioning was covaried out.

Attention

Developmental impact of frontal lobe injury in middle childhood.

Executive function of frontal lobe systems, like intelligent behavior, appears to demonstrate two major features: it is adaptive and goal-directed. Disruption of executive function following injury to the frontal lobes in childhood might be predicted to impact the trajectory of normal cognitive, behavioral, and social development. Case studies of two children injured at different ages showed the primary developmental impact to involve the behavioral and social realms. While cognitive development may be suspected to also be considerably influenced, assessment of changes in cognitive abilities by traditional psychometric means was found to be problematic. Psychometric changes were found to occur over a prolonged period of time, emphasizing the importance of documenting observations and chronicling postinjury events.

Brain Injuries