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PubMed2005

Childhood-onset growth hormone deficiency, cognitive function and brain N-acetylaspartate.

Cognitive deficits have been reported in adults with childhood-onset growth hormone (GH) deficiency. We evaluated cognitive deficits simultaneously with parameters for neuronal integrity using (1)H magnetic resonance spectroscopy (MRS) in a cross-sectional design. We studied 11 adults (mean age 24.5 years) with childhood-onset GH deficiency, which persisted after reaching final height. All subjects were evaluated after interruption of GH supplementation for at least 3 months. We performed neuropsychological assessment (NPA) using tests evaluating memory, mental processing speed, reading ability and executive functioning. MRS was used to assess brain N-acetylaspartate (NAA)/choline ratios. Data were compared with an age-, sex- and education-matched control group (n=9, mean age 27.3 years). NPA demonstrated attenuated performance of the patients in the delayed verbal memory recall score (P<0.05) and the trail making A test (P<0.05), a measure of planning of behavior, processing speed and attention. Other neuropsychological tests were not affected. NAA/choline ratios were significantly reduced (P<0.01) in GH deficient subjects. Specific cognitive defects indicating affected memory and attention were found in patients with childhood-onset GH deficiency. These defects occur simultaneously with reduced neuronal integrity.

Adolescent↗
PubMed2005

How our hands help us learn.

When people talk they gesture, and those gestures often reflect thoughts not expressed in their words. In this sense, gesture and the speech it accompanies can mismatch. Gesture-speech 'mismatches' are found when learners are on the verge of making progress on a task - when they are ready to learn. Moreover, mismatches provide insight into the mental processes that characterize learners when in this transitional state. Gesture is not just handwaving - it reflects how we think. However, evidence is mounting that gesture goes beyond reflecting our thoughts and can have a hand in changing those thoughts. We consider two ways in which gesture could change the course of learning: indirectly by influencing learning environments or directly by influencing learners themselves.

Cognition↗
PubMed2004

The multifocal visual evoked potential: an objective measure of visual fields?

We examined the effects of inter-modal attention and mental arithmetic on Humphrey visual field sensitivity and multifocal visual evoked potential (mfVEP) amplitude. Four normally sighted subjects (ages ranging from 24 to 58 years) participated in this study. Monocular visual field sensitivity was measured under two conditions: (1) standard testing condition and (2) while the subject performed a Paced Auditory Serial Addition Task (PASAT). Monocular mfVEPs were recorded in response to a 60-sector stimulus. The checkerboard pattern in each sector was contrast reversed according to a binary m-sequence. mfVEPs were recorded under two conditions: (1) standard testing conditions and (2) while the subject performed a PASAT. We found that, when compared to the no-task condition, all subjects had locations of significantly reduced Humphrey visual field sensitivities when performing the PASAT. In contrast, there were no significant decreases in mfVEP amplitude in any sector for any of the subjects while performing the PASAT. Our findings indicate that divided attention and ongoing mental processes did not affect the mfVEP. Therefore, the mfVEP provides an objective measure of visual field function that may be useful for some patients with unreliable automated static perimetry results.

Adult↗
PubMed1999

The differentiation of DSM-III-R psychotic depression in later life from nonpsychotic depression: comparisons of brain changes measured by multispectral analysis of magnetic resonance brain images, neuropsychological findings, and clinical features.

BACKGROUND: Psychotic depression has been proposed as a distinct subtype of major depression. There is considerable evidence for this in younger patients, although the neuroimaging has been rudimentary. Volumetric imaging studies are required of consecutive cohorts of patients with depression. METHODS: Ninety-nine consecutive elderly patients were diagnosed with DSM-III-R major depression. Eighteen were psychotic, and 81 were not. Sixty-six patients were given a neuropsychological test battery, and 44 had a magnetic resonance imaging brain scan. A model integrating clinical, psychological, and neuroimaging findings for the explanation of delusion formation during depression is proposed. RESULTS: Psychotic depression was characterized by worse physical health, more family history of depression, a poorer response to antidepressant drugs, and more severe lowering of mood; however, the strongest predictors of the presence of delusions were diencephalic atrophy, reticular activating system lesions, brain stem atrophy, and left-sided frontotemporal atrophy. The psychotic patients had poorer performance on tests of frontal lobe function and mental processing speed. CONCLUSIONS: In the elderly, psychotic depression is etiologically, clinically, and neuroradiologically distinct, and has different treatment requirements, from nonpsychotic major depression.

Age Factors↗
PubMed1999

Extrapyramidal symptoms and neuropsychological deficits in schizophrenia.

BACKGROUND: Extrapyramidal (EP) symptoms and neuropsychological (NP) deficits are both frequently present among schizophrenia patients. EP symptoms, such as motor slowing, could hinder performance on NP tests, yet little is known about the relationship between EP symptoms and NP functioning among schizophrenia patients. METHODS: Using a comprehensive NP test battery and standard ratings of EP symptoms and other psychiatric characteristics, we conducted a cross-sectional exploration of the association between EP symptoms and NP functioning among 96 middle-aged and elderly outpatients with schizophrenia. RESULTS: Severity of EP symptoms was associated with worse NP performance, particularly the areas of learning and motor skills. Regression analyses indicated that the relationship between EP symptoms and NP deficits was not accounted for by slowed motor or mental processing, demographic characteristics, severity of psychopathology, dyskinesia, or medication status. CONCLUSIONS: The pathophysiological mechanisms underlying EP symptoms and some NP deficits in schizophrenia may overlap.

Aged↗
PubMed1999

Defining the phenotype of schizophrenia: cognitive dysmetria and its neural mechanisms.

All research on schizophrenia depends on selecting the correct phenotype to define the sample to be studied. Definition of the phenotype is complicated by the fact that there are no objective markers for the disorder. Further, the symptoms are diverse, leading some to propose that the disorder is heterogeneous and not a single disorder or syndrome. This article explores an alternative possibility. It proposes that schizophrenia may be a single disorder linked by a common pathophysiology (a neurodevelopmental mechanism), which leads to a misconnection syndrome of neural circuitry. Evidence for disruption in a specific circuit is explored: the cortical-thalamic-cerebellar-cortical circuit (CCTCC). It is suggested that a disruption in this circuit leads to an impairment in synchrony, or the smooth coordination of mental processes. When synchrony is impaired, the patient suffers from a cognitive dysmetria, and the impairment in this basic cognitive process defines the phenotype of schizophrenia and produces its diversity of symptoms.

Brain Mapping↗
PubMed1997

Linking analytic performance goals to medical outcome.

As laboratorians relate analytic performance to medical goals, they face complex choices among competing subjective and objective criteria for the assessment of acceptable analytic error. Defining desirable performance as some fraction of physiologic variability provides potentially excessive benchmarks for quality. More important than the recognition of health are the clinical decisions which deal with diseases, particularly the latters' degrees of severity and the different medical actions these prompt. It is equally essential to take into account the reasoning by which physicians arrive at these decisions, since their mental processes condition desirable performance goals. Considering these modalities, a universal model of analytic performance requirements uniformly applicable to all measured parameters clearly cannot be devised. Rather, tolerance limits for analytic error must be tailored to specific medical problems. To facilitate this seemingly Herculean task, this paper develops concepts and principles derived from operation research, and illustrates their application by three examples. The generic conclusion evidenced by the latter is that the linkage between analytic performance goals and medical strategies is reciprocal, namely that outcome can just as well be optimized by tailoring medical strategy to existing analytic performance as by adapting analytic performance to medical strategy.

Clinical Medicine↗
PubMed1993

Preserved vocabulary acquisition in Down's syndrome: the role of phonological short-term memory.

We report the study of a 23-year-old Italian girl, FF, with Down's syndrome (trisomy 21). FF showed a remarkably good developmental acquisition of Italian language and vocabulary and was able to learn English and French, although the latter with less proficiency. FF showed an entirely preserved function of the phonological short-term store and articulatory rehearsal components of verbal short-term memory. By contrast, she was impaired in a wide range of tasks assessing verbal and non-verbal reasoning, visuo-spatial perception and memory, and verbal long-term memory. These findings, in line with evidence from brain-damaged patients, normal subjects and children, suggest that phonological short-term memory plays a crucial role in vocabulary acquisition, which may occur in the presence of substantial deficits of general intelligence and episodic memory.

Adult↗
PubMed2001

Prevalence and pattern of cognitive impairment in systemic lupus erythematosus patients with and without overt neuropsychiatric manifestations.

The prevalence and pattern of cognitive impairment in systemic lupus erythematosus (SLE) patients with (NPSLE) and without (nSLE) overt neuropsychiatric manifestations were investigated. Fifty-two nSLE patients, 23 NPSLE patients and 27 healthy controls were evaluated with a battery of standardized neuropsychological and psychological tests. Disease duration, disease activity index, and current corticosteroid therapy were collected. Cognitive impairment was identified in 14 (26.9%) and in 12 (52.2%) of subjects with nSLE and NPSLE, respectively. Both SLE groups showed a significant impairment compared with controls on tasks assessing verbal and non-verbal long-term memory, and visuoconstructional abilities. In addition, NPSLE patients reported worse performances than both nSLE patients and controls on task evaluating short-term visuospatial memory. NPSLE subjects were significantly more anxious and depressed compared to both nSLE subjects and controls. By multivariate analysis, only depression levels, among clinical variables, significantly predicted cognitive performance. This study shows that cognitive impairment occurs frequently in both nSLE and NPSLE subjects. The higher frequency in NPSLE may be related to coexisting depressive disturbances.

Adrenal Cortex Hormones↗
PubMed2002

Neuropsychological differentiation of small vessel disease, Alzheimer's disease and mixed dementia.

This study examined the neuropsychological profile of probable Alzheimer's disease (AD, n=72), vascular dementia due to diffuse subcortical small vessel disease (SVD, n=18) and mixed dementia (AD+SVD, n=18). Five simple tests were analysed, i.e. verbal recall and recognition memory, object naming, word fluency and clock reading. Pairwise discriminant analyses classified 79-83% of the cases correctly. Mixed dementia (MD) patients showed lower word fluency; otherwise, their profile was indistinguishable from AD. Recognition memory and clock reading were identified as predictors of SVD vs. AD diagnosis. The potential of single variables to distinguish the groups was tested by receiver operator characteristic curve analysis. A clock reading cut-off score close to maximum separated SVD from AD and MD. Recognition memory separated SVD from AD. These results show that neuropsychological tests can distinguish SVD and MD from AD with high sensitivity (88-94%). Due to the overlapping of scores and a higher prevalence of AD, specificity was moderate (65-76%) and positive predictive values were low, whereas sensitivity and negative predictive indices were high.

Aged↗
PubMed2002

Age-related white matter changes and cognitive impairment.

Age-related white matter changes (WMC) are a frequent finding in CT/MRI of older subjects. The role of WMC in cognitive impairment has been studied in community-dwelling and healthy old people, subjects with vascular risk factors, stroke patients, depressed and demented subjects. Although there are several negative studies, the majority of the evidence points towards an association between WMC and cognitive impairment. Speed of mental processes, attention, concentration, executive functions and visual spatial skills are the cognitive domains more commonly affected. The methodological problems of the negative studies are discussed, a number of unsolved issues are raised stressing the need for longitudinal studies of WMC with a adequate inception cohort.

Aged↗
PubMed2001

Elucidating the role of muscarinic receptors in psychosis.

Muscarinic receptors have been implicated in the regulation of cognition and psychosis based on pharmacological evidence from pre-clinical and clinical studies. Muscarinic agonists have shown promise in the clinic in improving cognition and reducing psychotic episodes in Alzheimer's patients. However, lack of selective muscarinic ligands has limited their use due to troublesome side effects observed at higher doses. Without selective ligands, it has been difficult to assign a specific muscarinic receptor subtype to these high order mental processes. Recent development of muscarinic receptor knockout mice has provided additional tools to investigate cognition and psychosis in behavioral assays and to determine the receptor subtypes associated with parasympathomimetic physiology. Biochemical studies indicate that the M1 receptor plays a significant role in regulating G alpha q-mediated signal transduction in the hippocampus and cortex. Behavioral studies suggest that the M4 receptor is involved in movement regulation and prepulse inhibition of the startle reflex, a measure of attention. These findings support a role for the development of M1 and M4 receptor agonists for diseases in which symptoms include cognitive impairment and psychotic behaviors.

Alzheimer Disease↗
PubMed2001

Remembering and knowing in a patient with preserved recognition and impaired recall.

ROB is a patient who has a severe deficit in recalling recently presented verbal material following rupture and repair of an anterior communicating artery aneurysm [Hanley JR, Davies ADM, Downes J, Mayes A. Cognitive Neuropsychology 1994;11:543-78; Hanley JR, Davies ADM. In: Parkin A, editor. Case Studies in the Neuropsychology of Memory. Hillsdale, NJ: Lawrence Erlbaum, 1997. p. 111-26]. Despite this, her performance on tests of recognition memory is comfortably within the normal range. In the present series of experiments, we investigated whether or not ROB's performance on tests of recognition memory might be associated with a disproportionately large number of correct decisions made on the basis of familiarity rather than contextual retrieval [e.g. Mandler G. Psychological Review 1980;87:252-71]. Contrary to this hypothesis, the results showed that ROB made a high proportion of remember decisions relative to know decisions in recognition [cf. Gardiner JM. Memory & Cognition 1988;16:309-13] and produced a high recollection score when conscious recollection and familiarity were placed in opposition to one another [cf. Jacoby LL, Woloshyn V, Kelley C. Journal of Experimental Psychology: General 1989;118:115-25.]. ROB's recognition memory performance therefore appears to be qualitatively as well as quantitatively similar to that found in the normal population. As ROB has suffered damage to both the fornix and the anterior thalamus, the results of the present study are consistent with the claim that damage to the extended hippocampal system has a much more severe effect on recall than on recognition [Aggleton JP, Shaw C. Neuropsychologia 1996;34:51-62; Aggleton JP, Saunders RC. Memory 1997;5:49-71]. The present results provide no support, however, for the additional suggestion [Aggleton JP, Brown MW. Behavioral and Brain Sciences 1999;22:425-56.] that the extended hippocampal system is necessary for recognition memory decisions that are based on contextual retrieval.

Decision Making↗
PubMed2003

Differences in word associations to pictures and words.

Normal subjects were asked to produce the "first word that comes to mind" in response to pictures or words that differed with respect to manipulability and animacy. In separate analyses across subjects and items, normal subjects produced a significantly higher proportion of action words (that is, verbs) to pictures as compared to words, to manipulable as compared to non-manipulable stimuli and to inanimate as compared to animate stimuli. The largest proportion of action words was elicited by pictures of non-living, manipulable objects. Furthermore, associates to words matched standard word associates significantly more often than those elicited by pictures. These data suggest that pictures and words initially contact different forms of conceptual information and are consistent with an account of semantic organization that assumes that information is distributed across different domains reflecting the mode of acquisition of that knowledge.

Adult↗
PubMed1999

Advantages of bias and prejudice: an exploration of their neurocognitive templates.

Bias is common in mental-processing tasks as diverse as target recognition, heuristic estimation and social judgment. This paper holds that cognitive biases stem from the covert operation of neural modules, which evolved to subserve adaptive behavior. Such modules can be innate or forged early in development. Research shows links between (i) biases in cognitive tasks and (ii) neural devices, which may mediate them. Evidence is included from biases that arise spontaneously in artificial neural networks during recognition/decision tasks. Two linked propositions follow. First, there are continuities in biasing strategies across different levels of cognitive processing. Second, a proclivity for stereotyping and prejudice depends on the biased functions of lower-level neural modules that promote adaptations to social environments. The propositions rest on evidence of biological preparedness for stereotyping and of deficits in social judgment in patients with neurological lesions. To test such claims, research studies are suggested at the boundary of cognitive neuroscience and social psychology. Advantages of bias and prejudice as evolved tools may include their: (1) speeding of scrutiny and improving of target detection in changing or uncertain situations; (2) aiding of a rapid choice of practical short-term rather than optimal longer term plans; (3) allowing appraisal of a workable world by creating fairly stable categories; (4) motivating of exploration and completion of problem-solving which might otherwise be abandoned too early. The biological priming of social biases need not mean that they are immutable; understanding them could lead to better ways of controlling them.

Cognition↗
PubMed1999

Contralateral induction by frequency spectrum in hallucinating schizophrenics.

Seventeen schizophrenic patients who had all experienced auditory hallucinations were compared with 14 subjects of a reference group on a test of contralateral induction. Contralateral induction means that a sound is illusively heard as coming from a location where it belongs according to its spectral content. The phenomenon is connected with a simultaneous relative elimination of masking. The schizophrenic subjects deviated from the reference group in several aspects. Some of them did not hear the sound being induced to the contralateral side, which it was for all reference subjects. Another subgroup of the schizophrenics noticed the induction unusually early with a prolonged experience of it, and finally some of them experienced the induction now and then. The aberrations were interpreted as rigidity of adaptation on the one hand and as effects of an enhanced sensitivity on the other. Discontinuity, meaning that the fluency in mental processing is broken, was interpreted to cause the ratings of the third group of schizophrenics in this sample, who heard the contralateral induction now and then. These phenomena are clearly reminiscent of descriptions in research reports, and witnessed by clinical experience of the schizophrenic disturbance. The results represent another example of discontinuous neurophysiological functions between neural systems and between individuals suffering from schizophrenia.

Adult↗
PubMed2002

Neural correlates of visuospatial imagery.

We studied changes in regional cerebral blood flow (rCBF) in 10 healthy right-handed subjects during a visuospatial imagery task. The subject's task consisted of drawing imagined lines connecting encircled numbers in ascending order and estimating the number of lines crossing. Compared with a control task in which there were no crossed lines, there were significant rCBF increases in the cingulate gyrus, the adjacent superior frontal gyrus and in the left inferior parietal cortex. The rCBF changes of the latter area correlated with task performance time. Since these activation areas are close to those in imagery of movement trajectories, we concluded that they appear to be a subsystem for processing mental visuospatial images.

Adult↗
PubMed2001

Psychophysiological correlates of individual differences in patterns of hemodynamic reactivity.

The present study delineates a method for the quantification of six hemodynamic reactivity patterns, in response to a laboratory stressor, and examines the psychophysiological correlates of individual differences in these patterns. One hundred and ninety-four young adult men and women participated in rest periods and two laboratory stressors, mental arithmetic and an anger recall interview. Measures were taken of blood pressure, heart rate, and cardiac output, from which total peripheral resistance was derived, as well as state reports of feelings during the tasks. Six hemodynamic reactor patterns were identified: Non-reactors, Mild Myocardials, Mild Vasculars, Myocardials, Vasculars, and Dual Reactors, each associated with a unique profile of cardiac output and total peripheral resistance change. Myocardial reactors to the interview had the highest resting levels of blood pressure and total peripheral resistance. Dual reactors had the largest increases in diastolic reactivity; Dual and Myocardial reactors had the largest increases in systolic reactivity. The extreme reactor groups (Dual, Myocardial, Vascular) all reported greater task invigoration than the Non-reactors, who reported greater efforts to relax. Reactor groups were similar on anger-related trait affect. Based on both resting blood pressure and magnitude of task-induced reactivity, Myocardial and Dual reactors may be at the greatest risk for subsequent hypertension.

Adolescent↗