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PubMed2002

Neuronal Ca2+ disregulation in diabetes mellitus.

The Ca(2+) hypothesis of brain ageing and dementia may account for part of the available data on the pathogenesis of dementia and certain neurodegenerative disorders. The hypothesis proposes that disturbances in the homeostasis of neuronal cytosolic free Ca(2+) are part of a final common pathway, ultimately leading to neuronal dysfunction and cell death. The hypothesis also proposes that a small change in cytosolic free Ca(2+) sustained over a long period of time will result in similar damage as a large change over a short period. Diabetes mellitus is associated with neurological complications in the peripheral and central nervous system, as reflected in peripheral neuropathy, modest cognitive impairments and an increased risk of dementia. In animal models of diabetes, learning impairments are associated with alterations in Ca(2+) -dependent forms of hippocampal synaptic plasticity. Disturbances in the homeostasis of cytosolic free Ca(2+) may present a final common pathway in the multifactorial pathogenesis of neurological complications of diabetes, which involves vascular changes, oxidative stress, and non-enzymatic protein glycation. In line with the Ca(2+) hypothesis of neurodegenerative disorders, a prolonged, small increase in basal cytosolic Ca(2+) levels indeed exists in sensory neurones of diabetic animals. In addition, Ca(2+) dynamics are affected. Ca(2+) channel blockers, such as nimodipine, have been shown to improve experimental peripheral neuropathy, through a vascular mechanism, possibly in combination with direct neuronal effects. Preliminary studies indicate that nimodipine may also improve Ca(2+)-dependent forms of synaptic plasticity in the hippocampus of diabetic rats.

Aging↗

PubMed1997

Life without ventilatory chemosensitivity.

In healthy humans ventilatory chemoreception results in exquisite regulation of arterial blood gases during NREM sleep, but during wakefulness other behavioral and arousal-related influences on breathing compete with chemoreceptive respiratory control. This paper examines the extent of chemoreceptive control of breathing within the normal physiological range in awake and sleeping humans and explores the consequences upon breathing of absent chemoreceptive function. Recent studies of subjects with congenital central hypoventilation syndrome (CCHS) demonstrate the extent of behavioral and arousal-related influences on breathing in the absence of arterial blood gas homeostasis. CCHS subjects lack chemoreceptor control of breathing and seriously hypoventilate during NREM sleep, requiring mechanical ventilation. Many CCHS subjects breathe adequately during many waking behaviors associated with arousal, cognitive activity or exercise--presumably reflecting input to the brainstem respiratory complex from the reticular activating system, the forebrain or mechanoreceptor afferents. In most situations, and despite changes in metabolism, the non-chemoreceptive inputs to breathing result in surprisingly well controlled arterial blood gases in CCHS patients.

Chemoreceptor Cells↗

PubMed2005

Modeling the minimally conscious state: measurements of brain function and therapeutic possibilities.

The minimally conscious state (MCS) defines a functional level of recovery following severe brain injuries. Patients in MCS demonstrate unequivocal evidence of response to their environment yet fail to recover the ability to communicate. Drawing on recent functional brain-imaging studies, pathological data, and neurophysiological investigations, models of brain function in MCS are proposed. MCS models are compared and contrasted with models of the vegetative state (VS), a condition characterized by wakeful appearance and unconsciousness. VS reflects a total loss of cognitive function and failure to recover basic aspects of the normal physiologic brain state associated with wakefulness. MCS may represent a recovery of the minimal dynamic architecture required to organize behavioral sets and respond to sensory stimuli. Several pathophysiological mechanisms that might limit further recovery in MCS patients are considered. Implications for future research directions and possible therapeutic strategies are reviewed.

Brain↗

PubMed2001

Sex differences in brain and behavior: emphasis on nicotine, nitric oxide and place learning.

Although males and females are unmistakably different, the recognition of sex as a key variable in science and medicine is considered a revolution in some circles. Sex differences transcend reproductive functions, are evident in the structural and functional organization of the brain, and are reflected in group differences in cognitive abilities and behavior. Males and females have different neural organizational patterns for information processing and different strategies in problem solving. Research on sex differences not only provides descriptive data, but also allows us to elucidate mechanisms that underlie our behavior. In this review, sex differences in the central actions of nicotine (an addictive substance) and nitric oxide, and performance on active avoidance and place learning tasks are discussed as examples, and biobehavioral approaches relating to these topics are presented.

Animals↗

PubMed1998

Human electroencephalographic (EEG) response to olfactory stimulation: two experiments using the aroma of food.

The present studies sought to examine the effect of olfactory stimulation on human Central Nervous System activity. In the first experiment (n = 21), EEG response to the 'synthetic' odours of chocolate, spearmint, almond, strawberry, vegetable, garlic and onion, and cumin or no odour was recorded from 19 electrodes (F3, F4, F7, F8, Fz, T3, T4, T5, T6, P3, P4, Pz, O1, O2, C3, C4, Cz) in all EEG frequencies (delta, theta, alpha, beta1 and beta2). Exposure to the odour of chocolate was associated with significant reductions in theta activity when compared with the odours of almond and cumin, with a trend towards significance when compared with no-odour control. Exposure to the odour of spearmint was associated with a significant reduction in EEG theta when compared with the no-odour control. No significant effects were observed in other frequencies. In a second experiment (n = 15), EEG response to the odours of real foods (chocolate, baked beans, rotting pork) and two controls (no odour and hot water) was recorded as in Experiment 1. The odour of chocolate was associated with significantly less theta activity than was any other stimulus. It is hypothesised that the alterations in theta reflect shifts in attention or cognitive load during olfactory perception, with a reduction in theta indicating a reduced level of attention.

Adolescent↗

PubMed2004

Integrated technology for evaluation of brain function and neural plasticity.

The study of neural plasticity has expanded rapidly in the past decades and has shown the remarkable ability of the developing, adult, and aging brain to be shaped by environmental inputs in health and after a lesion. Robust experimental evidence supports the hypothesis that neuronal aggregates adjacent to a lesion in the sensorimotor brain areas can take over progressively the function previously played by the damaged neurons. It definitely is accepted that such a reorganization modifies sensibly the interhemispheric differences in somatotopic organization of the sensorimotor cortices. This reorganization largely subtends clinical recovery of motor performances and sensorimotor integration after a stroke. Brain functional imaging studies show that recovery from hemiplegic strokes is associated with a marked reorganization of the activation patterns of specific brain structures. To regain hand motor control, the recovery process tends over time to bring the bilateral motor network activation toward a more normal intensity/extent, while overrecruiting simultaneously new areas, perhaps to sustain this process. Considerable intersubject variability exists in activation/hyperactivation pattern changes over time. Some patients display late-appearing dorsolateral prefrontal cortex activation, suggesting the development of "executive" strategies to compensate for the lost function. The AH in stroke often undergoes a significant "remodeling" of sensory and motor hand somatotopy outside the "normal" areas, or enlargement of the hand representation. The UH also undergoes reorganization, although to a lesser degree. Although absolute values of the investigated parameters fluctuate across subjects, secondary to individual anatomic variability, variation is minimal with regards to interhemispheric differences, due to the fact that individual morphometric characters are mirrored in the two hemispheres. Excessive interhemispheric asymmetry of the sensorimotor hand areas seems to be the parameter with highest sensitivity in describing brain reorganization after a monohemispheric lesion, and mapping motor and somatosensory cortical areas through focal TMS, fMRI, PET, EEG, and MEG is useful in studying hand representation and interhemispheric asymmetries in normal and pathologic conditions. TMS and MEG allow the detection of sensorimotor areas reshaping, as a result of either neuronal reorganization or recovery of the previously damaged neural network. These techniques have the advantage of high temporal resolution but also have limitations. TMS provides only bidimensional scalp maps, whereas MEG, even if giving three-dimensional mapping of generator sources, does so by means of inverse procedures that rely on the choice of a mathematical model of the head and the sources. These techniques do not test movement execution and sensorimotor integration as used in everyday life. fMRI and PET may provide the ideal means to integrate the findings obtained with the other two techniques. This multitechnology combined approach is at present the best way to test the presence and amount of plasticity phenomena underlying partial or total recovery of several functions, sensorimotor above all. Dynamic patterns of recovery are emerging progressively from the relevant literature. Enhanced recruitment of the affected cortex, be it spared perilesional tissue, as in the case of cortical stroke, or intact but deafferented cortex, as in subcortical strokes, seems to be the rule, a mechanism especially important in early postinsult stages. The transfer over time of preferential activation toward contralesional cortices, as observed in some cases, seems, however, to reflect a less efficient type of plastic reorganization, with some aspects of maladaptive plasticity. Reinforcing the use of the affected side can cause activation to increase again in the affected side with a corresponding enhancement of clinical function. Activation of the UH MI may represent recruitment of direct (uncrossed) corticospinal tracts and relate more to mirror movements, but it more likely reflects activity redistribution within preexisting bilateral, large-scale motor networks. Finally, activation of areas not normally engaged in the dysfunctional tasks, such as the dorsolateral prefrontal cortex or the superior parietal cortex in motor paralysis, might reflect the implication of compensatory cognitive strategies. An integrated approach with technologies able to investigate functional brain imaging is of considerable value in providing information on the excitability, extension, localization, and functional hierarchy of cortical brain areas. Deepening knowledge of the mechanisms regulating the long-term recovery (even if partial), observed for most neurologic sequelae after neural damage, might prompt newer and more efficacious therapeutic and rehabilitative strategies for neurologic diseases.

Animals↗

PubMed1999

Central nervous system effects of H1-receptor antagonists in the elderly.

BACKGROUND: The potential adverse central nervous system effects of H1-receptor antagonists have not been optimally studied in the elderly. OBJECTIVE: We hypothesized that newer H1-receptor antagonists such as cetirizine and loratadine would cause less central nervous system dysfunction than the older H1-receptor antagonists diphenhydramine and chlorpheniramine in this population, as they do in younger subjects. METHODS: We performed a randomized, double-blind, single-dose, placebo-controlled, 5-way crossover study in 15 healthy elderly subjects (mean age 71 +/- SD 5 years). On study days at least 1 week apart, they received cetirizine 10 mg, loratadine 10 mg, diphenhydramine 50 mg, chlorpheniramine 8 mg, or placebo. Outcome measures, recorded before and 2 to 2.5 hours after dosing were latency of the P300 event-related potential in which increased latency reflects a decreased rate of cognitive processing, visual analogue scale for subjective somnolence, and histamine skin tests for measurement of peripheral H1-blockade. RESULTS: The changes in P300 following each treatment yielded variances that were not equal (P > .05), precluding usual statistical analysis of the means. These variances were ranked: chlorpheniramine > diphenhydramine > loratadine > placebo > cetirizine. The rank of mean differences in the visual analogue scale increase from pre-dose baseline was: diphenhydramine > chlorpheniramine > cetirizine > loratadine > placebo. All H1-receptor antagonists suppressed the histamine-induced wheal and flare significantly compared to baseline. CONCLUSION: In the elderly, the new H1-receptor antagonists cetirizine and loratadine are less likely to cause adverse central nervous system effects than the old H1-antagonists chlorpheniramine or diphenhydramine, but this requires confirmation using additional objective tests of central nervous system function.

Aged↗

PubMed1991

Reduction of perseverative errors in patients with schizophrenia using monetary feedback.

The influence of monetary feedback on Wisconsin Card Sort Test (WCST) performance of 14 male schizophrenics was investigated. Patients were administered the test under standard instructions and with monetary feedback in counterbalanced order. Monetary reinforcement reduced perseverative errors and increased correct responses (p less than .05). These findings suggest that the WCST perseverative errors of schizophrenics reflect motivational as well as cognitive factors.

Adult↗

PubMed2004

Feelings or words? Understanding the content in self-report ratings of experienced emotion.

People differ in the extent to which their verbal reports of experienced emotion are valence focused or arousal focused. Three multimethod studies are reported to explore whether differential focus reflects individual differences in the cognitive structure of emotion language versus differences in phenomenological experience. Although there was some evidence that valence focus and arousal focus were linked to variations differences in cognitive structure, the findings are also consistent with the view that self-report ratings are being driven by the properties of the feelings that are being reported. Implications for the study of experienced emotion are discussed.

Adult↗

PubMed2001

A modern learning theory perspective on the etiology of panic disorder.

Several theories of the development of panic disorder (PD) with or without agoraphobia have emerged in the last 2 decades. Early theories that proposed a role for classical conditioning were criticized on several grounds. However, each criticism can be met and rejected when one considers current perspectives on conditioning and associative learning. The authors propose that PD develops because exposure to panic attacks causes the conditioning of anxiety (and sometimes panic) to exteroceptive and interoceptive cues. This process is reflected in a variety of cognitive and behavioral phenomena but fundamentally involves emotional learning that is best accounted for by conditioning principles. Anxiety, an anticipatory emotional state that functions to prepare the individual for the next panic, is different from panic, an emotional state designed to deal with a traumatic event that is already in progress. However, the presence of conditioned anxiety potentiates the next panic, which begins the individual's spiral into PD. Several biological and psychological factors create vulnerabilities by influencing the individual's susceptibility to conditioning. The relationship between the present view and other views, particularly those that emphasize the role of catastrophic misinterpretation of somatic sensations, is discussed.

Anxiety↗

PubMed1993

Early detection of Alzheimer's disease: a statistical approach using positron emission tomographic data.

Correlational analysis of regional cerebral glucose metabolism (rCMRglc) obtained by high-resolution positron emission tomography (PET) has demonstrated reduced neocortical rCMRglc interactions in mildly/moderately demented patients with probable Alzheimer's disease (AD). Thus, identification of individual differences in patterns of rCMRglc interactions may be important for the early detection of AD, particularly among individuals at greater risk for developing AD (e.g., those with a family history of AD). Recently, a statistical procedure, using multiple regression and discriminant analysis, was developed to assess individual differences in patterns of rCMRglc interdependencies. We applied this new statistical procedure to resting rCMRglc PET data from mildly/moderately demented patients with probable AD and age/sex-matched controls. The aims of the study were to identify a discriminant function that would (a) distinguish patients from controls and (b) identify an AD pattern in an individual at risk for AD with isolated memory impairment whose initial PET scan showed minor abnormalities, but whose second scan showed parietal hypometabolism, coincident with further cognitive decline. Two discriminant functions, reflecting interactions involving regions most involved in reduced correlations in probable AD, correctly classified 87% of the patients and controls, and successfully identified the first scan of the at-risk individual as AD (probability > 0.70). The results suggest that this statistical approach may be useful for the early detection of AD.

Aged↗

PubMed1985

Creative language abilities of deaf children.

The language flexibility and creativity of deaf children was investigated by having four deaf and four hearing 12-15-year-olds generate stories to experimenter-supplied themes. These were videotaped and examined for instances of nonliteral communication. Contrary to previous claims that deaf children are extremely rigid and literal in their language use, subjects here showed considerable use of creative language devices when evaluated in sign rather than vocal language. Deaf students produced traditional types of figurative contructions at a rate equal to their hearing age-mates and surpassed them in four other categories of nonliteral expression. These findings are discussed in terms of the cognitive skills required for and reflected by figurative language use and common assumptions concerning deaf children's related abilities.

Adolescent↗

PubMed1998

Speed of information processing in patients with multiple sclerosis.

To determine the extent to which multiple sclerosis (MS) slows cognitive processes, speeded tasks were administered to 11 patients with MS and to 11 comparison subjects without MS. On all tasks, patients with MS responded more slowly than comparison subjects. More important, response times (RTs) for patients with MS increased systematically as a function of RTs for comparison subjects, and the increase was best described by a power function. These data are consistent with the view that MS produces a general slowing of cognitive processes, and with the view that the cognitive slowing associated with aging reflects neural noise.

Adult↗

PubMed1999

The usefulness of the Brief Symptom Inventory in the neuropsychological evaluation of traumatic brain injury.

Changes in the health care delivery system are forcing clinicians to use less timely and more cost efficient measures. In rehabilitation, more efficient measures of emotional-behavioural functioning are being administered to patients with traumatic brain injury (TBI), including the Brief Symptom Inventory (BSI), a 53 item short version of the Symptom Checklist-90 that assesses nine different dimensions of emotional-behavioural functioning. Because the BSI was developed for use with psychiatric populations, research of the measure with TBI populations is needed. The current study evaluated the utility of the BSI in a sample of 62 patients (34 male, 28 female, average age 35, average education 12 years) with TBI evaluated as outpatients at a midwestern rehabilitation hospital. Results indicated that: (1) subjects endorsed clinically elevated distress on seven of the nine subscales when compared to the normative sample; (2) the Obsessive-Compulsive (OC) subscale achieved the highest t-score (70.31); 3) the most frequent two-point profiles included the OC-Somatic (21%) and OC-Psychoticism (13%) subscales; and (3) the Global Symptom Index was significantly correlated with all nine subscales. It was concluded that caution must be used when administering the BSI to individuals with TBI due to a lack of a TBI standardization sample, the limited number of test items per subscale, and questionable labels for the different subscales (e.g. OC subscale items appear to be more reflective of TBI-related cognitive impairment than obsessive-compulsive traits).

Adult↗

PubMedDate not supplied

Grammatical performance of children with language disorder on structured elicitation and narrative tasks.

The primary objective was to compare the grammatical output of children with language disorders on different tasks. Sixty-five children with language disorders, aged six to eleven, completed the syntactic formulation (elicitation) and narrative subtests from the Assessment of Comprehension and Expression 6-11 (Adams et al. 2001). Grammatical variables were computed for the narrative data and their relationship with the syntactic formulation subtest score examined. The use of ten specific constructions was compared in the two contexts. The syntactic formulation score correlated highly with narrative grammatical variables. However, for seven of the ten constructions, the elicitation task was more likely than the narrative to yield specific target structures. Structured elicitation is an efficient normative measure of grammatical production capacity. For specific structures, elicitation and narrative may give a different picture of output. Elicitation is more facilitative and may more closely reflect grammatical knowledge. Target structures were less likely to be used in the narrative, which reflects grammatical performance in a cognitively and linguistically demanding task.

Child↗

PubMed2006

Visuospatial skills and their association with math performance in girls with fragile X or Turner syndrome.

The present study was designed to assess object identification ("what") and location ("where") skills among girls with fragile X or Turner syndrome and girls with neither disorder. Participants completed standardized subtests of visual perception and tasks of visuospatial "what" and "where" memory. Girls with fragile X had average performance on most object identification tasks, yet 53% failed to accurately recreate the gestalt of a design during the "where" memory task. Fewer than 7% of girls in the Turner or comparison group made this error. Girls with Turner syndrome had lower scores and longer response times on object perception tasks and had poorer recall of location for internal features of the design on the "where" memory task, relative to girls in the comparison or fragile X group. When limiting analyses to IQ-matched samples, correlations between math and visual perception tasks emerged, but only for girls with fragile X. These results reflect important differences between two cognitive phenotypes and have implications for the role of visuospatial processing in early math performance.

Child↗

PubMed2003

Slowed lexical access is uniquely associated with positive and disorganised symptoms in schizophrenia.

INTRODUCTION: This study addressed the relationship of both semantic priming and slowed lexical access to the symptoms of schizophrenia, and evaluated their association with other neurocognitive deficits. METHODS: 57 outpatients with schizophrenia and 20 nonpsychiatric control subjects performed a lexical decision semantic priming task (LDT), and a brief neuropsychological battery. The schizophrenia group was also assessed with an extended Positive and Negative Symptom Scale. RESULTS: As expected, the schizophrenia group had significantly slower reaction times (RTs) than the control group, and poorer performance on most neuropsychological tasks. Both groups exhibited semantic priming effects in both automatic and controlled processing conditions; these effects were not significantly different between groups. RT was unrelated to age, illness duration, GAF scores, or neuroleptic dose; controlled semantic priming effects were related to illness duration only. RT to real word targets (but not to nonwords) on the LDT was significantly correlated with positive and disorganised, but not negative symptoms. The neurocognitive correlates of RT slowing were: full-scale IQ and verbal fluency, but not attention; working memory; episodic memory retrieval; executive function, or manual speed. Both controlled semantic priming effects as well as the difference between controlled and automatic priming effects were related to executive functions in general. Severity of symptoms in the three major symptom groups was generally unassociated with impairment on the neuropsychological battery. The associations of RT slowing to positive and disorganised symptoms remained even after controlling for each of the above clinical and neurocognitive measures. CONCLUSIONS: These findings suggest that in schizophrenia, slowed lexical access is uniquely related to positive and disorganised symptoms. This relationship is not accounted for by more general cognitive deficits, overall illness severity, or generalised effects of symptoms on cognitive function. This relationship may reflect a specific impairment in the access to semantic memory.

Journal Article↗

PubMed2007

Word-list-learning performance in younger and older adults: intra-individual performance variability and false memory.

We investigated the word-list-learning performance of younger and older adults over 4 consecutive days at different times of day to study age-related differences in consistency of performance over time and the influence of circadian variation on performance. Eighteen younger (M age, 23.4 years) and 18 older (M age, 73.3 years) men and women participated. The start time of testing alternated between morning and early evening across the 4 days of testing. On each test day, participants learned a different list of 15 unrelated words over four learning trials. As expected, younger adults performed better than older adults on immediate recall, delayed recall, and recognition. Contrary to our expectations, time of day did not significantly influence recall or recognition performance in either the older or younger adults. Older adults did show a greater incidence of false memory (i.e., previously learned list intrusions in free recall and false alarms in recognition) than younger adults. Older adults also exhibited greater intra-individual performance variability on the measures of false memory across test days. This variability was not related to circadian variation. False memory and variability of performance have both been linked to frontal systems dysfunction. The findings presented here are consistent with the notion that changes in cognition with aging in part reflect age-related decline in frontal lobe function.

Adult↗