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PubMed1988

Longitudinal study of the early neuropsychological and cerebral metabolic changes in dementia of the Alzheimer type.

To examine the progression of neuropsychologic and metabolic changes in the early stages of dementia of the Alzheimer type (DAT), we studied 11 midly demented patients longitudinally. Three aspects of neuropsychological function were measured: memory, attention to complex sets and abstract reasoning, and lateralized functions, i.e., language and visuoconstruction. Regional cerebral metabolic rates for glucose were measured in frontal, parietal, and temporal association cortices. Our results show that, in general, memory deficits are the first neuropsychological impairments to occur in DAT, followed by problems with attention to complex cognitive sets and abstract reasoning, which are followed in turn by deficits in language and visuospatial abilities. In addition, neocortical metabolic abnormalities usually precede impairment of neocortically mediated attention and abstract reasoning by 8 to 16 months, and precede impairment of neocortically mediated language and visuospatial function by 12 to 37 months. These findings suggest that the first nonmnestic neuropsychological consequence of neocortical physiological dysfunction in DAT is a loss of attentional capacity. Since neocortical metabolic changes generally precede the appearance of neocortically mediated neuropsychological dysfunction, physiologic dysfunction may exist for some time before cognition is affected.

Aged↗
PubMed2005

Early evaluation of the risk of functional decline following hospitalization of older patients: development of a predictive tool.

OBJECTIVE: To develop a predictive tool that could be used on admission to identify older hospitalized people at risk of functional decline 3 months after discharge. METHODS: This was a prospective cohort study that included 625 patients aged 70 years and older (mean age 80.0 +/- 5.6 years) hospitalized by the way of the emergency room, for at least 48 h, in two academic hospitals. Three months after discharge, 550 patients remained for analysis. On admission, people were assessed for premorbid functional status with the activities of daily living (ADL) scale and instrumental ADL scale. Demographic and medical data, including cognitive function, falls, polypharmacy, comorbidity, continence, mobility and self-rated health, were collected. ADL functioning was re-assessed at discharge and 1 and 3 months later. Functional decline was defined as the loss of at least one point on the ADL scale between the premorbid and 3-month evaluation. Univariate analyses were used to select variables associated with functional decline. A logistic regression model was then constructed to predict functional status 3 months after discharge. RESULTS: Three months after discharge, 165 (31.5%) patients had declined. The predictive tool SHERPA includes five factors: age, impairment in premorbid instrumental ADLs, falls in the year before hospitalization, cognitive impairment (Abbreviated Mini Mental State below 15/21) and poor self-rated health. Sensitivity and specificity were 67.9% and 70.8%, respectively. CONCLUSIONS: Older people are at high risk of functional decline following hospitalization. On admission, a simple instrument can easily identify these patients, even though the performance of this instrument is moderate.

Activities of Daily Living↗
PubMed2004

Primitive roles for inhibitory interneurons in developing frog spinal cord.

Understanding the neuronal networks in the mammal spinal cord is hampered by the diversity of neurons and their connections. The simpler networks in developing lower vertebrates may offer insights into basic organization. To investigate the function of spinal inhibitory interneurons in Xenopus tadpoles, paired whole-cell recordings were used. We show directly that one class of interneuron, with distinctive anatomy, produces glycinergic, negative feedback inhibition that can limit firing in motoneurons and interneurons of the central pattern generator during swimming. These same neurons also produce inhibitory gating of sensory pathways during swimming. This discovery raises the possibility that some classes of interneuron, with distinct functions later in development, may differentiate from an earlier class in which these functions are shared. Preliminary evidence suggests that these inhibitory interneurons express the transcription factor engrailed, supporting a probable homology with interneurons in developing zebrafish that also express engrailed and have very similar anatomy and functions.

Action Potentials↗
PubMed2006

Hemispheric lateralization of cognitive functions in children with centrotemporal spikes.

We assessed the impact of unilateral epileptic foci in benign idiopathic partial epilepsy of childhood with rolandic discharges (BECT) on performance and hemispheric specialization in lateralized cognitive functions. Six children with BECT with a left-sided focus (BECT-L), 6 children with BECT with a right-sided focus (BECT-R), and 12 control children were tested in verbal, visual-spatial, and visual-attention tasks, with visual hemifield presentation. Children with BECT-R were impaired in the visual-spatial task relative to those with BECT-L, and the typical left-hemisphere (LH) advantage was not reported in the verbal task in children with BECT-L. Additionally, the classic global superiority effect was lacking in children with BECT-R, which may be due to impaired performance of the right hemisphere specialized in global (vs local)-level processing. These data argue for the deleterious effect of epileptic discharges per se on cognitive functions in the developing brain, and the decisive role of epileptic focus lateralization in specific cognitive impairments and hemispheric specialization.

Child↗
PubMed1993

Role of the tectal and posterior commissures in lateralization of the avian brain.

We report a role for the tectal and posterior commissural system (TC/PC) in functional lateralization of the chicken brain. Unlike the corpus callosum of mammals which is thought to generate lateralization, the TC/PC in the chicken brain is shown to suppress lateralization. The TC/PC was sectioned on day 2 post-hatching. The performance of this TC/PC-sectioned group on a battery of monocular, behavioural tests was compared to a sham-lesioned group and an untreated group. The first of these tests measured pecking and fear responses to a small bead. In both the sham-lesioned group and the untreated group there was no change in the pecking response over repeated presentations of the bead, nor was there a left eye/right eye difference in either of these groups. In contrast, the TC/PC-sectioned group showed increased pecking of the bead each time it was presented. This increase in the pecking response was significantly greater for those chicks tested using the right eye than for those tested using the left eye. That is, sectioning the TC/PC caused a lateralized response which was not seen in either of the control groups, demonstrating that the intact TC/PC suppresses lateralization at the tectal level. In the other tasks (latency to peck at a mealworm and a visual discrimination learning task) the untreated controls showed clear left eye/right eye differences while the sham-lesioned group and the TC/PC-sectioned group showed no lateralization. It is suggested that for these two tasks the loss of lateralization is due to lesioning an area in the midbrain but not to sectioning the TC/PC.

Animals↗
PubMed2005

Sign and speech: amodal commonality in left hemisphere dominance for comprehension of sentences.

The neural basis of functional lateralization in language processing is a fundamental issue in systems neuroscience. We used functional MRI (fMRI) to examine hemispheric dominance during the processing of signed and spoken sentences. By using tasks involving comprehension of sentences (Sc) and sentential non-word detection (Sn), we compared different groups and stimulus conditions. Under the sign condition with sentence stimuli in Japanese Sign Language (JSL), we tested two groups of subjects: Deaf signers (Deaf) of JSL, and hearing bilinguals (children of Deaf adults, CODA) of JSL and Japanese (JPN). Under the speech condition, we tested hearing monolinguals (Mono) of JPN with auditory JPN stimuli alone (AUD), or with an audiovisual presentation of JPN and JSL stimuli (A&V). We found that the overall bilateral activation patterns under the four experimental conditions of Deaf, CODA, AUD and A&V were almost identical, despite differences in stimuli (JSL and JPN) and groups (Deaf, CODA and Mono). Moreover, consistently left-dominant activations involving frontal and temporo-parietal regions were observed across all four conditions. Furthermore, irrespective of the modalities of sign and speech, the main effects of task (Sc-Sn) were found primarily in the left regions: the ventral part of the inferior frontal gyrus (F3t/F3O), the precentral sulcus, the superior frontal gyrus, the middle temporal gyrus, the angular gyrus and the inferior parietal gyrus. Among these regions, only the left F3t/F3O showed no main effects of modality condition. These results demonstrate amodal commonality in the functional dominance of the left cortical regions for comprehension of sentences, as well as the essential and universal role of the left F3t/F3O in processing linguistic information from both signed and spoken sentences.

Acoustic Stimulation↗
PubMed1969

Changes in leucocyte migration after renal transplantation.

The leucocyte migration test, an in-vitro measure of cellular immunity, has been used to follow the changes in cell-mediated hypersensitivity to kidney and histocompatibility antigens in three patients after renal transplantation.Inhibition of leucocyte migration, indicating strong sensitization to the antigens used, occurred in each patient, starting five to seven days after transplantation. Satisfactory renal function had not been established in any of the patients at this time. In one case inhibition of leucocyte migration persisted almost continuously until the 24th day and was associated with poor renal function proved histologically to be due to rejection. Treatment with increased dosage of prednisone was associated with a rapid reversion to normal of the migration index and improvement in renal function. Later, inhibition of migration occurred again, and shortly afterwards the graft ceased to function. In the other two cases the migration index became normal without alteration in immunosuppressive therapy and a satisfactory diuresis followed. It is suggested that this simple test should prove useful in the specific diagnosis of rejection and in control of immunosuppressive therapy.

Adolescent↗
PubMed2000

Interhemispheric asymmetries of the modular structure in human temporal cortex.

Language-relevant processing of auditory signals is lateralized and involves the posterior part of Brodmann area 22. We found that the functional lateralization in this area was accompanied by interhemispheric differences in the organization of the intrinsic microcircuitry. Neuronal tract tracing revealed a modular network of long-range intrinsic connections linking regularly spaced clusters of neurons. Although the cluster diameter was similar in both hemispheres, their spacing was about 20 percent larger in the left hemisphere. Assuming similar relations between functional and anatomical architecture as in visual cortex, the present data suggest that more functionally distinct columnar systems are included per surface unit in the left than in the right area 22.

Adult↗
PubMed2002

The relationship between abstinence for one year following pretreatment assessment and alcohol use and other functioning at two years in individuals presenting for alcohol treatment.

OBJECTIVE: The purpose of this study was to replicate and extend research that shows abstinence from alcohol during the first year following treatment predicts better longer term functioning in alcohol use and other areas. METHOD: The subjects were 187 men and women who had participated in a clinical trial of the differential effectiveness of two behavioral treatments for alcohol problems as a function of subject characteristics. All subjects who participated in this phase of the study were classified as either abstinent from alcohol or not based on their drinking behavior during the first 12 months following treatment initiation. Subjects' alcohol use and other behaviors were evaluated for Months 13-24. The primary dependent variables of interest were alcohol use, self-efficacy, and psychological functioning. RESULTS: A comparison of the two abstinence groups showed that abstainers, compared to drinkers, had less alcohol use, higher self-efficacy, and better psychological functioning. CONCLUSIONS The results suggest the association is robust between abstinence during the first year following treatment initiation or cessation and later functioning, and extend this finding to include psychological functioning. Future research should focus on possible mediators of the abstinence correlations with later behavior that are of theoretical and practical importance, and on specifying gradients of duration of abstinence or other drinking patterns reflecting improvement and their relationship to longer term functioning.

Adult↗
PubMed2006

Changes in joint position sense after conservatively treated chronic lateral ankle instability.

Improvement of ankle proprioception through physiotherapy (a.k.a. proprioceptive training) is a widely accepted conservative treatment modality of chronic functional lateral ankle instability. Clinical studies provided controversial data on its proprioceptive effect. Aim of this study was to gain evidence on the efficacy of proprioceptive training on ankle joint position sense. Ten patients (five males and five females, aged 23.3+/-5.4 years) were treated conservatively for chronic lateral ankle instability with a special training programme over 6 weeks. For the assessment of joint position sense we used the slope-box test, first applied and described by Robbins et al. (Br J Sports Med 29:242-247, 1995). The test was performed before the start and after the end of the training programme, measuring joint position sense on 11 different slope amplitudes in four directions (anterior, posterior, lateral and medial) in random order each on both ankles. Comparisons were made between pre- and post-training results as well as versus a control-group of ten healthy athletes. Overall the proprioceptive sensory function of the studied group has improved, but this improvement was not significant in all directions. Only two patients have shown significant improvement of joint position sense in all directions (mean estimate error improvement: 2.47 degrees ), while conservative treatment was partially successful in five others (mean estimate error improvement: 0.73 degrees ). The follow-up results of these seven patients were comparable with the values measured in the control-group. Three patients did not show any improvements (mean estimate error improvement: -0.55 degrees ) (overall difference between improving and non-improving patients: P<0.0001). Mean absolute estimate error profiles of the seven improving patients became similar to the profiles of healthy athletes, while these changes could not be observed in the case of the three non-improving participants. Proprioceptive rehabilitation programme can be an effective method in order to improve impaired joint position sense function. After 6 weeks non-responding patients can be well identified, and considered for other treatment modalities. The determination of the effective length of the programme however needs further evaluation. Still, changes in the proprioceptive sensory function of the ankle plantarflectors indicate the preventive effect of the training programme. Furthermore, our results support the theory of simultaneous function of different mechanoreceptor-systems.

Adult↗
PubMed2001

Complexity of olfactory lateralization processes revealed by functional imaging: a review.

Currently available techniques used in neurosciences and particularly cerebral imaging are contributing to a better understanding of human perception and the treatment of sensorial information. In this field, the chemical senses (taste and smell) have received little attention when compared with the auditory, visual and tactile senses. Nevertheless, recent research has been trying to overcome this. Brain regions involved in the processing of olfactory information have been investigated in several studies including a large number dealing with the question of lateralization. However, functional asymmetry in olfaction has still not been resolved and the resulting data have not been homogeneous. In this field, the contribution of cerebral imaging studies is very important insofar as it shows that the processes of functional lateralization in olfaction depend on many factors (nature of stimulus, nature of task, characteristics of subjects ...) that future research will have to consider.

Animals↗
PubMed2005

Versatility of the reverse lateral arm flap in the treatment of post-burn antecubital contractures.

If they are not managed with proper treatment and rehabilitation, full thickness burns involving the cubital fossa may result in severe contractures that may impair upper extremity functions. Later release of these contractures discloses a large soft tissue defect that should be replaced. We used reverse lateral arm flaps for coverage of the cubital fossa in 11 selected cases of antecubital contracture. Ten flaps survived totally while we experienced one distal partial necrosis, which was later treated by skin grafting. We achieved considerable functional improvements in all cases. Although fasciocutaneous flaps offer the advantage of using regional tissue in a single stage, few versatile local flaps relying on the vascular anatomy around the elbow joint are available for cubital fossa coverage. Being a rapid, easy and one-staged procedure with no necessities for sacrifice of a major artery or muscle and for a long-term immobilization of the involved joints, reverse lateral arm flaps appears to be advantageous in comparison to other options for coverage of the cubital fossa defects after the release of antecubital contractures.

Adult↗
PubMed2004

Ephrin-B2 reverse signaling is required for axon pathfinding and cardiac valve formation but not early vascular development.

Vascular development begins with the formation of a primary vascular plexus that is rapidly remodeled by angiogenesis into the interconnected branched patterns characteristic of mature vasculature. Several receptor tyrosine kinases and their ligands have been implicated to control early development of the vascular system. These include the vascular endothelial growth factor receptors (VEGFR-1 and VEGFR-2) that bind VEGF, the Tie-1 and Tie-2 receptors that bind the angiopoietins, and the EphB4 receptor that binds the membrane-anchored ligand ephrin-B2. Targeted mutations in the mouse germline have revealed essential functions for these molecules in vascular development. In particular, protein-null mutations that delete either EphB4 or ephrin-B2 from the mouse have been shown to result in early embryonic lethality due to failed angiogenic remodeling. The venous expression of EphB4 and arterial expression of ephrin-B2 has lead to the speculation that the interaction of these two molecules leads to bidirectional signaling into both the receptor-expressing cell and the ligand-expressing cell, and that both forward and reverse signals are required for proper development of blood vessels in the embryo. Indeed, targeted removal of the ephrin-B2 carboxy-terminal cytoplasmic tail by another group was shown to perturb vascular development and result in the same early embryonic lethality as the null mutation, leading the authors to propose that ephrin-B2 reverse signaling directs early angiogenic remodeling of the primary vascular plexus [Cell 104 (2001) 57]. However, we show here that the carboxy-terminal cytoplasmic domain of ephrin-B2, and hence reverse signaling, is not required during early vascular development, but it is necessary for neonatal survival and functions later in cardiovascular development in the maturation of cardiac valve leaflets. We further show that ephrin-B2 reverse signaling is required for the pathfinding of axons that form the posterior tract of the anterior commissure. Our results thus indicate that ephrin-B2 functions in the early embryo as a typical instructive ligand to stimulate EphB4 receptor forward signaling during angiogenic remodeling and that later in embryonic development ephrin-B2 functions as a receptor to transduce reverse signals involved in cardiac valve maturation and axon pathfinding.

Animals↗
PubMed2006

The ATP-sensitive potassium (KATP) channel-encoded dSUR gene is required for Drosophila heart function and is regulated by tinman.

The homeobox transcription factor Tinman plays an important role in the initiation of heart development. Later functions of Tinman, including the target genes involved in cardiac physiology, are less well studied. We focused on the dSUR gene, which encodes an ATP-binding cassette transmembrane protein that is expressed in the heart. Mammalian SUR genes are associated with K(ATP) (ATP-sensitive potassium) channels, which are involved in metabolic homeostasis. We provide experimental evidence that Tinman directly regulates dSUR expression in the developing heart. We identified a cis-regulatory element in the first intron of dSUR, which contains Tinman consensus binding sites and is sufficient for faithful dSUR expression in the fly's myocardium. Site-directed mutagenesis of this element shows that these Tinman sites are critical to dSUR expression, and further genetic manipulations suggest that the GATA transcription factor Pannier is synergistically involved in cardiac-restricted dSUR expression in vivo. Physiological analysis of dSUR knock-down flies supports the idea that dSUR plays a protective role against hypoxic stress and pacing-induced heart failure. Because dSUR expression dramatically decreases with age, it is likely to be a factor involved in the cardiac aging phenotype of Drosophila. dSUR provides a model for addressing how embryonic regulators of myocardial cell commitment can contribute to the establishment and maintenance of cardiac performance.

ATP-Binding Cassette Transporters↗
PubMed1994

Abdominal syndromes and functional ability in the elderly.

Data concerning a random cohort of 1,119 70-year-old subjects were analyzed to evaluate the association between Upper Dyspepsia and Irritable Bowel Syndrome and functional ability. Seven hundred and thirty-four subjects were interviewed about abdominal symptoms and were visited at home by an occupational therapist who evaluated their functional ability. Among the survivors, 94% participated in a follow-up study five years later. Functional ability was registered on validated scales constructed for its measurement in a normal elderly population. It was found that both syndromes occurred more often among subjects with reduced functional ability. A significant association was found between the occurrence of Upper Dyspepsia and a reduction of mobility and lower limb function, and between reduced functional ability and Irritable Bowel Syndrome at the five-year follow-up. It is concluded that abdominal syndromes are associated to functional ability, suggesting that there is a diffuse disorder affecting both smooth and striated muscles.

Activities of Daily Living↗
PubMed1995

Emergence of functional circuits in ferret visual cortex visualized by optical imaging.

The emergence of functional lateral interactions in ferret visual cortex was monitored using high speed optical imaging of voltage-sensitive dye signals in brain slices. Prior to the time of eye opening, lateral activation was restricted to a narrow columnar region. During the week following eye opening, the extent of lateral propagation of activity more than doubled. Selective interruption of specific pathways in the slice, combined with pharmacological and anatomical experiments, determined that this lateral propagation was mediated by horizontal projections made within layer 2/3. These results indicate that functional horizontal interactions emerge only after axons begin branching and in parallel with, but not prior to, the refinement of orientation selectivity.

Age Factors↗