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An update on falls.

PURPOSE OF REVIEW: Falls among elderly persons create immense social problems because of their association with physical decline, serious psychosocial consequences, negative impact on the quality of life, and markedly reduced survival. In addition, falls pose high costs to the public health service. For these reasons, falls remain a popular topic for research. Here, we review several interesting developments that have been published during the past year. RECENT FINDINGS: Considerable attention has been focused on early identification of fallers and prevention strategies for falls or injuries. A remaining challenge is to implement such strategies into daily clinical practice, at acceptable costs and with good acceptance. New evidence has been generated to suggest the importance of high-level processing for postural control, but it remains difficult to predict falls based upon a simple dual tasking test. Neuroimaging studies are now beginning to provide new insights into the role of cortical structures in balance regulation, and how cortical dysfunction might contribute to falls. Posturography studies using multidirectional moving platforms or computer models of balance have provided new insights into falling mechanisms, in particular the role of abnormal protective responses (stepping or grasping) and the negative effects of stiffening. Other studies have shown how a fear of falling, a common sequel to falls, may lead to secondary degeneration of postural control, thus completing a vicious loop. SUMMARY: While these examples illustrate that falls research is very much ongoing, one cannot speak of true progress until the scientific evidence can be implemented into real life, with falls being prevented effectively in individual cases.

Accidental Falls↗

Disturbances of cortical development.

The development processes coinciding in formation of cerebral cortex were presented. On this background may arise the cortical developmental abnormalities. The review of principal cortical malformations include the 1) agyria-pachygyria - lissencephaly type I, 2) polymicrogyria, 3) disorganized cortical structure - lissencephaly type II, 4) minor cortical developmental anomalies and 5) other cortical dysplasia syndromes. It will help to reconstruct the pathomechanism of cortical abnormal development from early occurring primary errors to late changes in which coincide necrotic lesions. The presented material illustrate the role of time of occurrence and intensity of damage in final result of pathologic developmental processes.

Cerebral Cortex↗

[Arousal thresholds during stimulation of brain structures in nonanesthetized cats].

In cats, there was no apparent difference between the average low thresholds for evoking EEG arousal when stimulating the mesencephalic RF, thalamic CM or some cortical structures (sensorimotor area, inferior part of auditory Ep). Most of other cortical points had much higher thresholds (g. lateralis anterior, g. suprasylvius posterior, g. ectosylvius med. and sup.). The possible role of some cortical and mesencephalic structures in the brain activating mechanisms is discussed.

Animals↗

Long-term potentiation in the reciprocal corticohippocampal and corticocortical pathways in the chronically implanted, freely moving rat.

The hippocampus and adjacent cortical structures, including the entorhinal, perirhinal, and parahippocampal cortices, appear to serve as an integrated memory system. This extended hippocampal system is believed to influence memory and consolidation through an extensive set of reciprocal connections with widespread areas of the neocortex. Long-term potentiation (LTP) has been well-examined in the intrinsic connections of the hippocampus and neocortex. However, LTP in the pathways and structures thought to convey information between the hippocampus and neocortex has received little attention. If these pathways and structures are involved in information storage, and if LTP reflects a general synaptic encoding mechanism, then these systems are also likely to support LTP. In this paper we discuss a series of experiments aimed at investigating LTP in the efferents between the hippocampus and neocortex in chronically implanted animals. In the first experiment, the efferents of the perirhinal cortex were stimulated. LTP in the dentate gyrus (DG) reached asymptote more slowly than is typically seen following perforant path stimulation, whereas the frontal area (M1) reached asymptote more quickly than reported following corticocortical stimulation. The DG and M1 LTP was long-lasting, but entorhinal cortex LTP had decayed to baseline levels after a week. In the second experiment, the hippocampal efferents were stimulated. The perirhinal, entorhinal, and frontal cortex showed a similar slow potentiation, with only the perirhinal cortex levels returning to baseline after a week. In the third experiment, the projections from M1 were tested. The perirhinal cortex and hippocampus showed a long-lasting LTP. Although LTP was found in all pathways examined, there were differences in the induction and decay rate, and these properties may correspond to differences in learning rate and longevity of information storage.

Animals↗

Numerical instabilities in bone remodeling simulations: the advantages of a node-based finite element approach.

Long bone structure occurs in two distinct forms. The bone mass near the joint is primarily found in a distributed, porous trabecular structure, while in the diaphyses a tubular cortical structure is formed. It seems likely that these two observed morphologies come about, at least in part, as a mechanical adaptation to the different mechanical demands in the two regions. Mathematical formulations of this dependency have been proposed, thus facilitating numerical simulations of bone adaptation. Recently two types of discontinuities have been observed in these simulations. The first type (near-field) appears in areas near distributed load application and is characterized by a 'checkerboard' pattern of density wherein adjacent remodeled elements alternate between low and high density. The second type of discontinuity (far-field) appears remote from the load application and is characterized by strut or column-like regions of elements which become fully compact bone while adjacent regions are fully resorbed. In fact, the far-field discontinuity is an accurate representation of bone physiology and morphology since it is consistent with the appearance of cortical bone in the diaphysis. On the other hand, the near-field discontinuity, appears in a region where continuous distributions of intermediate apparent densities (trabecular bone) are expected. This finding may cause some to question whether a single continuum formulation of bone remodeling can predict both discontinuous far-field behavior and continuous near-field behavior. We describe a node-based implementation of current continuum bone remodeling theories which eliminates the spurious near-field discontinuities and preserves the anatomically correct far-field discontinuities, thus indicating that a single biological process may be at work in forming and maintaining both far-field and near-field morphologies.

Algorithms↗

Prepulse inhibition and fear-potentiated startle are altered in tissue inhibitor of metalloproteinase-2 (TIMP-2) knockout mice.

The ability to discriminate between potential dangers and recall those stimuli is essential for survival. This emotional learning requires the involvement of higher brain structures, including the amygdala, hippocampus and related cortical structures. Long-term changes in synaptic transmission and structure are important for the establishment and consolidation of fear memory. The structural changes associated with this synaptic plasticity likely require alterations in the composition of the extracellular matrix (ECM). ECM integrity is maintained by the opposing action of matrix metalloproteinases (MMPs) and their specific inhibitors, tissue inhibitors of metalloproteinases (TIMPs). To date, no studies have examined the role of MMPs or TIMPs in conditioned fear. Here, we show that neither male nor female mice deficient in TIMP-2 (knockout) exhibit prepulse inhibition of the startle reflex, suggesting deficits in pre-attentional sensorimotor gating. In addition, knockout mice and mice expressing a mutant truncated TIMP-2 (knock-down) show deficits in fear-potentiated startle. This is the first report of a phenotype for the TIMP-2(-/-) mice and suggests that TIMP-2 may play a role in the synaptic plasticity underlying learning and memory.

Acoustic Stimulation↗

Broca's area and the ventral premotor cortex in language: functional differentiation and specificity.

The idea is put forward that Broca's area (BA 44/45) and the left ventral premotor cortex (BA 6) together with the frontal operculum support different functions during language processing. While BA 44/45 is seen to be increasingly activated whenever the internal re-construction of a hierarchical structure from a sequential input is necessary, BA 6 is involved in the processing of local structural dependencies. This functional differentiation is discussed in the context of the neurocytoarchitectonical differentiation between agranular structure characterizing BA 6 and a dysgranular cortical structure characterizing BA 44/45. This differentiation is exemplified in the domain of language, but is possibly applicable to non-language domains.

Comprehension↗

Manganese deposition in basal ganglia structures results from both portal-systemic shunting and liver dysfunction.

BACKGROUND & AIMS: Manganese (Mn) deposition could be responsible for the T(1)-weighted magnetic resonance signal hyperintensities observed in cirrhotic patients. These experiments were designed to assess the regional specificity of the Mn increases as well as their relationship to portal-systemic shunting or hepatobiliary dysfunction. METHODS: Mn concentrations were measured in (1) brain samples from basal ganglia structures (pallidum, putamen, caudate nucleus) and cerebral cortical structures (frontal, occipital cortex) obtained at autopsy from 12 cirrhotic patients who died in hepatic coma and from 12 matched controls; and from (2) brain samples (caudate/putamen, globus pallidus, frontal cortex) from groups (n = 8) of rats either with end-to-side portacaval anastomosis, with biliary cirrhosis, or with fulminant hepatic failure as well as from sham-operated and normal rats. RESULTS: Mn content was significantly increased in frontal cortex (by 38%), occipital cortex (by 55%), pallidum (by 186%), putamen (by 66%), and caudate (by 54%) of cirrhotic patients compared with controls. Brain Mn content did not correlate with patient age, etiology of cirrhosis, or history of chronic hepatic encephalopathy. In cirrhotic and portacaval-shunted rats, Mn content was increased in pallidum (by 27% and 57%, respectively) and in caudate/putamen (by 57% and 67%, respectively) compared with control groups. Mn concentration in pallidum was significantly higher in portacaval-shunted rats than in cirrhotic rats. No significant changes in brain Mn concentrations were observed in rats with acute liver failure. CONCLUSIONS: These findings suggest that brain Mn deposition results both from portal-systemic shunting and from liver dysfunction.

Animals↗

Can male decorticate rats copulate?

Sexually experienced or naive male rats, subjected to neocortex removal or neocortex plus hippocampus removal, were paired with female rats for up to 180 days and compared with control rats with respect to success and latency to impregnate the female. All of the control rats and half of the brain-damaged rats successfully impregnated female rats at least once. Success was not correlated with lesion type or presurgical experience. The brain-damaged rats took longer to impregnate the females than control rats. Since the ablations were extensive, more than 95% of the neocortex in many rats, the study shows that decorticate rats can copulate. Presumably the intact subcortical structures are sufficient for male copulation, but cortical structures in some way facilitate rapid female impregnation.

Animals↗

Subcortical neglect: quantitation, anatomy, and recovery.

Fifteen patients with right hemispheric subcortical infarcts localized by CT or MRI were evaluated with a neglect testing battery. Trimodal extinction was present in one case, visual extinction in three, tactile in three, and auditory in six. Although frequent (10 cases), hemispatial neglect was rarely severe (3 cases). Three cases recovered completely. Large posterior internal capsule lesions were associated with more frequent impairment on a cancellation test. The probable mechanism of hemispatial neglect was attentional in one case and intentional in six. Visual and auditory extinction is explained by striatonigral mechanisms. Although subcortical structures participate in attentional and intentional behavior, cortical structures can substitute for their functions.

Attention↗

Morphological study of organotypic cerebellar cultures.

Organotypic cerebellar cultures from 8-days-old (P8) mouse pups were studied following 11 days of in vitro (I IDIV) culturing. The cerebellar cytoarchitectonic structure was maintained in most parasagittal cerebellar cortical slice cultures (also containing the deep cerebellar nuclei). The two main extrinsic excitatory inputs (the climbing and the mossy fibers) seem to be replaced by other axonal types: in the molecular layer mostly by parallel fibers (for climbing fibers) and in the granular layer by intrinsic mossy fiber collaterals of local excitatory interneurons, the unipolar brush cells. However, in a few organotypic cultures, which (although preserving the trilaminar cerebellar cortical structure) were "granuloprival" but also contained some of the deep cerebellar nuclei, the participation of extracortical axons from the deep cerebellar nuclei in the replacement of the missing afferents is suggested.

Afferent Pathways↗

Spinal myoclonus with giant somatosensory evoked potentials and enhanced long-loop reflex: a case report.

We describe a patient with an ischaemic lesion of the cervical spinal cord who presented with clinical evidence of stimulus-sensitive, multisegmental myoclonic jerks restricted to the truncal and proximal limb muscles and accompanied by electrophysiological features (giant somatosensory evoked potentials and enhanced long-loop reflex) of cortical myoclonus. We hypothesize that these features might result from a loss of inhibitory influences on the sensory input to cortical structures: a concomitant contribution of spinal and cortical hyperexcitability seems to have played a crucial role in inducing myoclonus in our patient.

Aged↗

Quantitative autoradiography of [3H]norharman [( 3H]beta-carboline) binding sites in the rat brain.

The anatomical distribution of [3H]norharman binding sites was determined by quantitative autoradiography in rat brain slices. They are enriched in hypothalamic, thalamic, accumbens and amygdaloid nuclei as well as in hippocampal, neocortical and olfactory-related structures. The distribution pattern differs from that of other previously described receptors or binding sites (e.g. monoamine oxidase, benzodiazepine, tryptamine, 5-hydroxytryptamine receptors (5-HT1A, 5-HT1B, 5-HT1C, 5HT2], which suggests that a unique class of [3H]norharman binding sites exists in the rat brain. The findings are consistent with previous experiments which showed high affinity binding sites for [3H]norharman in rat brain membranes (KD 1.552 nM; autoradiography KD 5.5 nM). A correspondence in the displacing activity of drugs was found for both methods (crude membrane fraction: harman much greater than tryptamine much greater than 5-hydroxytryptamine greater than N-methyl-beta-carboline-3-carboxamide (FG 7142) = diazepam; autoradiography: harman much greater than tryptamine much greater than FG 7142 greater than 5-hydroxytryptamine greater than diazepam). Provided that the binding sites represent functional receptors, the present anatomical findings may explain the biological effects of norharman, e. g. pro-conflict behaviour (limbic-hypothalamic structures), tonic-clonic convulsions (limbic-cortical structures) and alterations of locomotor activity (accumbens nucleus).

Alkaloids↗

Changes of motor evoked potential amplitudes following magnetic stimulation after hyperventilation.

The influence of hyperventilation on amplitudes of motor evoked potentials (MEP) following cortical and root magnetic stimulations was tested in ten healthy volunteers. Hyperventilation significantly increased MEP amplitude following cortical stimulation (p < 0.01) but failed to change MEP amplitude following root stimulation. This finding is compatible with the concept of hyperventilation as a promoter of greater excitability at the level of cortical structures. The provoking method applied during magnetic cortical stimulation might be a useful procedure in studying some functional affections associated with hyperventilation, such as hyperventilation tetany or panic disorder.

Adult↗

Photochemically induced cortical infarction in the rat. 1. Time course of hemodynamic consequences.

Alterations in local CBF (LCBF) were assessed autoradiographically in the rat at several time points following photochemically induced cortical infarction. Cortical infarction of consistent size and location was produced by irradiating the brain with green light through the intact skull for 20 min following the systemic injection of rose bengal. A consistent pattern of altered LCBF was recorded in both ipsilateral and contralateral brain regions over the course of the study. At 30 min, a severely ischemic zone surrounded by regions of cortical hyperemia was apparent. LCBF was also depressed relative to control values in ipsilateral cortical regions remote from the irradiated area, while contralateral cortical structures were mildly hyperemic. By 4 h, the zone of severe ischemia had enlarged and its margins were no longer hyperemic. Ipsilateral cortical and some subcortical structures demonstrated significantly depressed levels of LCBF. At 5 days, LCBF throughout both ipsilateral and contralateral cortices was depressed compared with control values. By 15 days, LCBF had returned to control levels in most brain structures shown histopathologically not to be irreversibly damaged. The temporal sequence and magnitude of these hemodynamic alterations are consistent with findings in clinical studies in which repeated measurements of CBF have been carried out in patients with acute stroke. The ability to produce a cortical infarct that results in a consistent pattern of altered CBF should facilitate the investigation of stroke mechanisms responsible for these hemodynamic abnormalities.

Animals↗

Pathophysiology of generalized penicillin epilepsy in the cat: the role of cortical and subcortical structures. I. Systemic application of penicillin.

The mechanism of precipitation of generalized epileptiform discharges in feline generalized penicillin epilepsy, a model of human generalized corticoreticular ('centrencephalic') epilepsy, was studied in acute and chronic experiments in cats with implanted skull and intracerebral electrodes. Single shock and low frequency repetitive stimulation of subcortical sites from which prior to penicillin administration spindle activity and recruiting responses could be elicited, readily triggered epileptiform discharges in the same animals after penicillin. These structures comprised the intralaminar and midline thalamic nuclei, the neostriatum, and some posterior thalamic association nuclei (Pulvinar and nucleus lateralis posterior). Subcortical and cortical structures which prior to penicillin elicited neither spindle activity nor recruiting responses were significantly less effective in triggering generalized epileptic bursts after penicillin injection. The probability with which such bursts were elicited from these structures was still, however, in many instances above chance level. It is concluded that the generalized epileptiform discharges in feline generalized penicillin epilepsy can be triggered from a large number of brain sites, but most reliably so from subcortical nuclei involved in spindle generation and recruiting responses. The experimental evidence presented still does not allow one to determine whether epileptic alteration of neuronal function in this form of epilepsy primarily resides in cortical or subcortical nerve cells or in both.

Animals↗

Experience-dependent structural plasticity in cortex heterotopic to focal sensorimotor cortical damage.

Structural plasticity following focal neocortical damage in adult rats has recently been found to be sensitive to postinjury rehabilitative training. Experience on a complex motor skills task, the acrobatic task, after unilateral lesions of the forelimb representation region of the sensorimotor cortex (FLsmc) enhanced synaptic structural changes in the cortex contralateral and homotopic to the lesions. Using tissue from this previous study, the present study examined whether a heterotopic region of the sensorimotor cortex of either hemisphere, the hindlimb representation area (HLsmc), would undergo structural changes following unilateral FLsmc lesions and whether these changes would also be sensitive to postinjury training on the acrobatic task. Stereological methods for light and electron microscopy were used to assess structural changes in lesion or sham-operated rats following 28 days of postoperative acrobatic training or simple repetitive exercise (motor controls). In the HLsmc contralateral to the lesions of rats receiving acrobatic training, there was a subtle, but significant, increase in cortical volume and in layer II/III neuropil and dendritic volume per neuron in comparison to shams. In rats receiving simple exercise after the lesions, these changes were not significantly different from shams. Acrobatic training also prevented a loss of cortical volume in the HLsmc adjacent to the lesion in comparison to shams. These data suggest that behavioral training following cortical injury facilitates structural plasticity in behaviorally relevant areas of the neocortex other than the homotopic cortex contralateral to the lesion. This structural plasticity might be relevant to the development of behavioral compensation after cortical injury.

Animals↗