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handedness in engineering and psychology students.

Patterns of handedness were compared in engineering and psychology students using a questionnaire developed by Oldfield (1971). Engineering students are highly selected in terms of mathematico-spatial skills while psychology students are representative of typical undergraduate populations. In general the incidence of right- and left-handedness was according to expectation for the two groups. However, the engineering sample exhibited a significantly greater dextrality then the psychologists. Some implications of this finding were discussed.

Engineering↗

Does age of menarche affect the ultimate level of verbal and spatial skills?

Waber's claim that individual differences in cognition reflect variations in rate of maturation was tested by correlating the performance of 50 right-handed females in verbal and spatial tasks with their age of onset of menstruation. No significant relationships emerged. This suggested that Waber's findings, obtained on adolescents who were still maturing, do not apply to subsequent cognitive outcomes during adulthood.

Adolescent↗

Selective reminding in normal and demented aged people: auditory verbal versus visual spatial task.

A new test of visual spatial learning (VS) which uses the rationale of selective reminding and evaluates memory and learning of spatial positions of objects was presented. This was compared with the auditory verbal selective reminding (AV) in regard to normal aging and dementia. The results showed that the performance of VS declines with age more steeply than those of AV. Factor analyses showed that the performance of VS to be factorially independent of that of AV, and showed that VS can account for most of the decline in performance of normal aged people. The performance on VS of demented patients correlated well with the serverity of dementia. The comparison between multi-infarct dementia and Alzheimer type dementia indicated that severe impairment of VS with relative preservation of AV is a distinctive pattern of Alzheimer type. These results suggest that VS is a useful tool to evaluate memory decline with aging and that it can be useful in the clinical diagnosis of dementia.

Aged↗

Effect of spatial ability and sex on inter- and intrahemispheric correlation of EEG activity.

Inter- and intrahemispheric correlation of the EEG activity at rest was computed in two groups of men and women, between 17 and 21 years old, with extreme degrees of spatial ability (SA) evaluated by the Spatial Relations Subtest of the Differential Aptitudes Test (DAT). Interhemispheric (INTERr) and intrahemispheric (INTRAr) EEG correlations were computed by means of Pearson product-moment coefficients for 5 EEG bands after digitally filtering with an FFT. Women showed significantly higher INTERr of alpha 1 between left and right centrals, lower INTRAr between right frontal and right central regions and lower INTRAr within the left than in the right hemisphere. High SA subjects showed lower INTERr between left and right frontal derivations and higher INTRAr between frontal and parietal and between central and parietal regions of both hemispheres. Sex interacted with SA in INTRAr of alpha between right frontal and right temporal regions with high SA women showing lower INTRAr than low SA women and than men. The present results indicate a different inter- and intrahemispheric functional organization in men and women and in subjects with high and low spatial ability.

Adolescent↗

Event-related potentials during memorization of spatial locations in the auditory and visual modalities.

Event-related potential (ERP) studies of working memory have used delayed S1-S2 match-to-sample tasks in which S1 is held in memory for comparison with S2. ERP negativities in the S1-S2 interval have been interpreted either in terms of working memory operations, or in terms of general preparatory motor processing. Two experiments (N = 20 each) were carried out to explore the nature of ERP negativities in a visuospatial memory task and in an auditory spatial memory task, respectively. In the experimental condition, subjects had to memorize the location of S1 (S1-memorize) so as to respond whether S2 appeared in the same spatial location (S2-memorize). In the control condition, subjects were requested to ignore S1 (S1-passive), and to respond whether S2 matched or not a target location predetermined at the beginning of the trial block (S2-pressing). Results support the two main conclusions of Martin-Loeches et al. (Electroenceph. clin. Neurophysiol., 1994, 91: 363-373). Firstly, that the encoding into memory of spatial location is associated with an ERP negative wave over the brain areas putatively associated with the processing of sensory information (i.e. right parieto-occipital for the visual task; fronto-central and left temporal areas for the auditory task). Secondly, the P300 does not seem to be an important ERP feature related to spatial location encoding and retaining into memory. Despite the distinct scalp distribution of these memory-related, modality-specific ERP negativities, they also showed a considerable degree of temporal synchronicity across modalities.

Adolescent↗

Pre-training blocks the improving effect of tetrahydroaminoacridine and D-cycloserine on spatial navigation performance in aged rats.

We investigated the effect of pre-training on the improvement of spatial navigation performance provided by a cholinesterase inhibitor, tetrahydroaminoacridine (3 mg/kg, i.p.), and a positive modulator of NMDA receptor, D-cycloserine (10 mg/kg, i.p.), or their combination in aged rats. Pre-training consisted of spatial or non-spatial conditions and took place in either the same or a separate room. We found that any kind of pre-training was able to eliminate the enhancing effect of tetrahydroaminoacridine and D-cycloserine on spatial navigation. However, none of these pre-training conditions was able to block the age-related deficit in spatial navigation. These results indicate that tetrahydroaminoacridine and D-cycloserine, separately or in combination, do not themselves alleviate the age-related spatial memory deficit, but may enhance procedural aspects of water maze learning in aged rats.

Aging↗

SR 141716A enhances spatial memory as assessed in a radial-arm maze task in rats.

A tonically active endogenous cannabinoid system has been proposed to modulate learning and memory. The purpose of the present study was to determine whether administration of the cannabinoid CB(1) receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl (SR 141716A) would enhance memory as assessed in an eight-arm radial maze task. Because the high degree of choice accuracy in the standard radial-arm maze procedure precludes the possibility of detecting memory enhancement, the difficulty of the task was increased by imposing a delay of varying durations between a two-phase procedure consisting of acquisition and test phases. Significantly fewer errors were committed during the test phase following an injection of SR 141716A than the vehicle treatment. These results provide additional evidence supporting the hypothesis that endogenous cannabinoid systems play a role in memory processes.

Analysis of Variance↗

Involvement of 5-hydroxytryptamine neuronal system in Delta(9)-tetrahydrocannabinol-induced impairment of spatial memory.

The present study investigated the involvement of the serotonin (5-hydroxytryptamine, 5-HT) neuronal system in the Delta(9)-tetrahydrocannabinol-induced impairment of spatial memory in the eight-arm radial maze in rats. Delta(9)-Tetrahydrocannabinol (6 mg/kg, i.p.), which impairs spatial memory, significantly increased the 5-HT content in the ventral hippocampus. A microdialysis study showed that Delta(9)-tetrahydrocannabinol (6 mg/kg, i.p.) decreased 5-HT release in the ventral hippocampus. The 5-HT precursor, 5-hydroxy-L-tryptophan (5-HTP; 50 mg/kg, i.p.), the 5-HT re-uptake inhibitor, clomipramine (0.01 and 0.1 mg/kg, i.p.), the 5-HT receptor agonist, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT; 0.01 and 0.03 mg/kg, i.p.), and the 5-HT(2) receptor agonist, 1-(2,5-dimethoxy 4-iodophenyl)-2-amino propane (DOI; 10 microg/kg, i.p.), significantly attenuated the Delta(9)-tetrahydrocannabinol-induced impairment of spatial memory. These results suggest that the 5-HT neuronal system may be involved in the Delta(9)-tetrahydrocannabinol-induced impairment of spatial memory.

5-Hydroxytryptophan↗

A synthetic ceramide analog ameliorates spatial cognition deficit and stimulates biosynthesis of brain gangliosides in rats with cerebral ischemia.

A synthetic ceramide analog, L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (L-PDMP) upregulates ganglioside biosynthesis in several cell lines. In cultured cortical neurons, neurotrophic effects of L-PDMP on neurite outgrowth and synaptic activity were demonstrated. In addition, it was found that L-PDMP could ameliorate the spatial cognition deficit in rats with ischemia. To elucidate this effect, we evaluated the effect of L-PDMP on brain ganglioside biosynthesis and its therapeutic efficacy against spatial cognition deficit in rats made ischemic. Rats were trained for 2 weeks, using an 8-arm radial maze task, and then forebrain ischemia was induced. L-PDMP was injected i.p. at 40 mg/kg twice a day starting from day 1 or 3 after ischemia induction for 6 or 4 days, respectively. The first study showed significantly reduced spatial cognition deficit at 12 h after the final drug administration, and L-PDMP tended to attenuate apoptosis in hippocampal CA1. To examine the effect of L-PDMP on brain ganglioside biosynthesis, N-[3H]acetyl-D-mannosamine was infused into the lateral ventricle via an injection cannula at 12 h after the final drug administration. After 4 h, the brain gangliosides were purified and analyzed. Upregulation of ganglioside biosynthesis by L-PDMP was observed on days 3 and 5 after ischemia. These results are an indication that L-PDMP may ameliorate spatial cognition deficit by upregulating ganglioside biosynthesis in ischemic brain.

Animals↗

SA4503, a novel cognitive enhancer with sigma1 receptor agonist properties, facilitates NMDA receptor-dependent learning in mice.

The selective sigma1 receptor agonist 1-(3,4-dimethoxyphenethyl)-4-(3-phenyl propyl)piperazine dihydrochloride (SA4503) was reported to reverse the amnesia induced by the muscarinic receptor antagonist scopolamine at sub-mg/kg doses. We examined its effect on the learning impairment induced in mice by the non-competitive NMDA receptor antagonist dizocilpine. Learning capacities were evaluated using spontaneous alternation in the Y-maze for spatial working memory, and step-down type passive avoidance. SA4503 (0.03-1 mg/kg s.c.) attenuated the dizocilpine (0.15 mg/kg i.p.)-induced memory deficits following a bell-shaped curve in both tests. These effects of SA4503 were blocked by haloperidol (0.05 mg/kg i.p.), implicating sigma1 receptors. SA4503 also reversed the alternation deficit induced by N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 mg/kg i.p.) at the same dosage, indicating that it acted on working memory through the nitric oxide (NO)-mediated signalling pathway. Furthermore, progesterone (2 mg/kg s.c.) blocked the SA4503 effects in the dizocilpine- and L-NAME-amnesia models, in accordance with the purported neurosteroids/sigma1 receptors interaction. These results demonstrate a promising neurobehavioural profile of SA4503, a ligand equally efficient to reverse the deficit in the glutamatergic as well as in the cholinergic amnesia model. Pertinent informations on the potential mechanism of the anti-amnesic effects of sigma1 receptor ligands were also obtained.

Amnesia↗

Facilitation of cognitive functions by a specific alpha2-adrenoceptor antagonist, atipamezole.

The present experiments investigated the effects of a specific and potent alpha2-adrenoceptor antagonist, atipamezole (as a stimulator of the noradrenergic system) on cognitive performance in rats. Atipamezole enhanced the acquisition of a linear-arm maze test and also improved the choice accuracy of poorly performing rats in a delayed (20 min) three-choice maze test. Furthermore, atipamezole improved the achievement of a one-trial appetite-maze when injected immediately after teaching, thus having an effect on consolidation. Atipamezole clearly impaired the acquisition of the active avoidance test. The present results indicate that stimulation of noradrenergic system by atipamezole improves the performance of animals in tasks assessing relational learning and memory, possibly affecting attention, short-term memory and the speed of information processing. It has also an effect on a consolidation process unrelated to attentional or motivational mechanisms. In a stressful test. stimulation of noradrenaline release leads to impairment of performance.

Adrenergic alpha-2 Receptor Antagonists↗

Downregulation of brain mineralocorticoid and glucocorticoid receptor by antisense oligodeoxynucleotide treatment fails to alter spatial navigation in rats.

Adult male Brown Norway rats were long-term intracerebroventricularly (i.c.v.) infused with antisense oligodeoxynucleotides (18-mer, double endcapped phosphorothioate protected) targeting either mineralocorticoid or glucocorticoid receptor mRNA, or received the respective mixed bases sequence or vehicle. Mineralocorticoid receptor-mixed bases and glucocorticoid receptor-mixed bases oligodeoxynucleotide infusion (1 microg/0.5 microl/h) over a time period of seven days did not alter hippocampal mineralocorticoid receptor and glucocorticoid receptor binding when compared to vehicle treatment. In contrast, i.c.v. administration of mineralocorticoid receptor, as well as glucocorticoid receptor-antisense over the same time period resulted in a significantly reduced binding of mineralocorticoid receptor and glucocorticoid receptor in the hippocampus [mineralocorticoid receptor-antisense group approx. 72% of mineralocorticoid receptor-mixed bases and vehicle groups (100%); glucocorticoid receptor antisense group approx. 77% of glucocorticoid receptor-mixed bases and vehicle]. The specificity of these antisense effects is indicated by the finding that rats treated with mineralocorticoid receptor-antisense did not show any changes in glucocorticoid receptor and vice versa. Animals treated according to this infusion protocol and tested in the Morris water maze for their spatial navigation abilities failed to show significant differences among the groups. These data indicate that a reduction of hippocampal mineralocorticoid receptor or glucocorticoid receptor binding capacity by 20-30% does not interfere with spatial navigation.

Animals↗

Metrifonate improves working but not reference memory performance in a spatial cone field task.

The effects of metrifonate (3, 10 and 30 mg/kg, p.o.) on the working and reference memory performance of the rat were assessed in a spatial cone field task. The highest dose of metrifonate (30 mg/kg) improved the working memory performance, whereas none of the doses affected the reference memory performance. Other parameters of spatial discrimination performance were not affected by metrifonate treatment. The present results suggest that metrifonate has cognition-enhancing properties which are likely to be related to aspects of (spatial) working memory.

Animals↗

Dynamic measurement of internal solid displacement in articular cartilage using ultrasound backscatter.

Mechanics of articular cartilage can be represented using poroelastic theories where fluid and solid displacements are viscously coupled to create a time-dependent spatially heterogeneous behavior. In recent models of this tissue, finite element methods have been used to predict tissue deformation as a function of time for adult articular cartilage bearing a characteristic depth-dependent structure and composition. However, current experimental methods are limited in providing verification of these predictions. The current study presents an apparatus for imaging the radial displacement profile of cartilage in unconfined compression using an ultrasound technique called elastography. We acquired ultrasound A-scans across the lateral diameter of full-thickness cartilage disks containing a thin layer of underlying bone, during axial compression. Elastography was then applied to correlate temporally sequential A-scans to estimate the solid radial displacement profile in articular cartilage while it undergoes compression and stress-relaxation. Both time-dependent and depth-dependent solid radial displacement profiles were obtained with a precision better than 0.2 micro The results generally agree with predictions of poroelastic models, demonstrating lateral expansion with an effective Poisson's ratio just after completion of the compression phase of the mechanical tests reaching values from 0.18 to 0.4 (depending on compression speed), followed by contraction to lower values. A more restricted movement was observed at both the articular surface and near to the subchondral bone than at regions midway between these two locations.

Animals↗

Neuropsychologic effects of stroke in children with sickle cell anemia.

We examined the nature and extent of neuropsychologic impairment in children with sickle cell anemia (SCA) with or without stroke. Twenty-nine children with SCA received cranial magnetic resonance imaging. Strokes were classified into three groups: diffuse cortical stroke (n = 11), anterior stroke (n = 6), or none (n = 12). Children with SCA and 20 age-matched sibling control subjects then received a neurologic examination and a neuropsychologic battery of tests that included motor, verbal, spatial, attentional, and memory measures. Tests of spatial function showed that children with diffuse cortical strokes were impaired, whereas children with anterior lesions had intrusions of irrelevant material during list recall. There were no significant differences between children with stroke and sibling control subjects on motor, verbal, or memory measures. Six children had evidence of stroke on magnetic resonance imaging without any history of a damaging neurologic event. These children had impaired neuropsychologic performance relative to that of sibling control subjects in a pattern similar to that of children with overt stroke. Children with SCA without stroke did not differ from sibling control subjects on any measure. Our results indicate that overt and silent strokes result in lesion-specific neuropsychologic deficits in children with SCA.

Adolescent↗

Spatiotemporal gait patterns during over ground locomotion in major depression compared with healthy controls.

Alterations of locomotion are frequent, observable features of patients suffering from depression and have been investigated in these patients by actigraphy, cinematography and ground reaction forces. However, spatiotemporal parameters and neurophysiological mechanisms of gait have not yet been studied in depth in depression. The relationship between spatial and temporal parameters may yield insight into the pathophysiology of altered movements in depression. Therefore, gait patterns were quantitatively assessed and analysed in depressed subjects (n=16) and compared to matched healthy controls. Spatiotemporal gait parameters were measured during over ground walking at self-selected walking speed on a walkway previously validated in healthy subjects and used for orthopaedic and neurological patients. Compared to controls, depressed patients showed significantly lower gait velocity (p<0.001), reduced stride length (p<0.005), double limb support (p<0.005) and cycle duration (p<0.005). There was a significant correlation between cadence and gait velocity in depressed patients (r=0.51, p<0.05), but not in healthy controls (r=0.11, p>0.05). In patients with major depression, reduced gait velocity was associated with stride hypometria and increased cycle duration. Velocity was associated with cadence in depressed patients but not in healthy controls. The results may indicate possible deficiencies in the motor control system in depression. These first results about alterations of spatiotemporal gait patterns in depression warrant further longitudinal and experimental studies.

Adult↗

Administration of caspase 3 inhibitor during and after status epilepticus in rat: effect on neuronal damage and epileptogenesis.

Symptomatic temporal lobe epilepsy typically develops in three phases: brain damage --> epileptogenesis --> spontaneous seizures (epilepsy). The challenge is to prevent epileptogenesis after injury. We hypothesized that alleviation of damage by caspase inhibitors will reduce epileptogenesis or at least have disease-modifying effects (less severe epilepsy, milder cognitive decline). Epileptogenesis was triggered by amygdala stimulation-induced status epilepticus (SE) in rats and spontaneous seizures were monitored with video-electroencephalography (EEG). First, we tested the neuroprotective effect of a 1-week treatment with caspase 1, 3 or 9 inhibitors (3 micro g/d/i.c.v., started 3 h after the beginning of SE). The least damage to the hippocampus was observed in animals treated with the caspase 3 inhibitor (z-DEVD-fmk) which reduced the enzyme activity to 6% of that in the vehicle group. Thus, z-DEVD-fmk was chosen for long-term studies, in which the treatment regime remained the same except the dose was doubled (6 micro g/d/i.c.v.). Video-EEG monitoring was performed for 3 to 4 weeks, starting either 8 or 14 weeks after SE. One group of animals was tested in water-maze and fear-conditioning tests, and all animals were perfused for histological analysis. Treatment with the caspase 3 inhibitor neither prevented the development of epilepsy, nor had any disease-modifying effects. Mossy fibre sprouting, however, was reduced. The present data indicate that administration of z-DEVD-fmk monotherapy was not antiepileptogenic despite its short-term neuroprotective effects. These findings challenge the idea that prevention of cell death is the primary target for the development of antiepileptogenic compounds.

Animals↗