Biped Gait Analysis based on Forward Kinematics Modeling using Quaternions Algebra

ABSTRACT Gait is the main locomotion way for human beings as an autonomous decision. Due to the increase in people with walking disabilities, the precision in gait analysis for purposes in clinical diagnosis, sports medicine or biomechanical research for the design of assistive technologies is of special relevance. The literature reports notable contributions in technological developments with diverse applications; and in some cases, algorithms for characterization and gait analysis; however, more studies related to gait kinematics are necessary, such as the solution proposed in this work. In this paper, we focus on studying the forward kinematics of the lower limbs in human gait, using in a novel way quaternions algebra as mathematical tool and comparative analysis with classical methods is established. Gait analysis unlike other works is carried out by evaluating the rotational and tilting movements of the pelvis, flexion-extension of the hip and knee; as well as dorsiflexion and plantarflexion of the ankle. Finally, an assessment of normal, mild crouch and severe crouch gaits in the three anatomical planes is performed; and a metric based on the Euclidean norm in the cartesian space is used to evaluate these gaits.

Hippocampal effects of neuronostatin on memory, anxiety-like behavior and food intake in rats.

A 13-amino acid peptide named neuronostatin (NST) encoded in the somatostatin pro-hormone has been recently reported. It is produced throughout the body, particularly in brain areas that have significant actions over the metabolic and autonomic regulation. The present study was performed in order to elucidate the functional role of NST on memory, anxiety-like behavior and food intake and the hippocampal participation in these effects. When the peptide was intra-hippocampally administered at 3.0 nmol/µl, it impaired memory retention in both, object recognition and step-down test. Also, this dose blocked the hippocampal long-term potentiation (LTP) generation. When NST was intra-hippocampally administered at 0.3 nmol/µl and 3.0 nmol/µl, anxiolytic effects were observed. Also, the administration in the third ventricle at the higher dose (3.0 nmol/µl) induced similar effects, and both doses reduced food intake. The main result of the present study is the relevance of the hippocampal formation in the behavioral effects induced by NST, and these effects could be associated to a reduced hippocampal synaptic plasticity.

Different chronic cocaine administration protocols induce changes on dentate gyrus plasticity and hippocampal dependent behavior.

Hippocampus is a limbic structure that participates in learning and memory formation. Specifically the dentate gyrus has been described as a hippocampal subregion with high rates of plasticity and it is targeted by different psychoactive drugs modulating synaptic plasticity. Repeated cocaine administration induces sensitization to the locomotor effects and it is believed that sensitization involves the same mechanisms of drug seeking and relapse. Although, the mechanisms underlying sensitization is not fully understood. In this work we investigated the impact of repeated intraperitoneal administration of cocaine (15 or 20 mg/kg/day along 5 or 15 days respectively; and 15 mg/kg/day along 5 day followed by a challenge dose after three days of withdrawal) on the dentate gyrus synaptic plasticity, differentiating between sensitized and nonsensitized rats. Furthermore, we correlated changes on the hippocampal synaptic plasticity to memory retention. Our results revealed that the prevalence of cocaine sensitization (around 50%) was identical in all protocols used. The results found in the threshold to generate LTP were similar for all protocols used, being the threshold values cocaine-treated groups (sensitized and nonsensitized) significantly reduced compared to controls, observing the highest reduction in the sensitized group. Moreover, we observed a facilitated retention of recent memory formation only in sensitized animals the nonsensitized subjects remained at the control levels. In conclusion, sensitization to cocaine generates a high efficiency of hippocampal synaptic plasticity that may underlie the aberrant engagement of learning processes occurred during drug addiction.

The plastic phenomenon underlying the associative processes in the addictive properties of diazepam and other psychoactive drugs.

Benzodiazepines are commonly prescribed for the therapy of disorders such as anxiety and sleep disturbance, but develop dependence in many patients. In this review we discuss the impact of different brain areas that modulate the reward system in the development of tolerance and dependence to benzodiazepine and the associative processes underlying those fenomena.

Huperzia saururus, activity on synaptic transmission in the hippocampus.

Huperzia saururus (Lam.) Trevis. (Lycopodiaceae) known as cola de quirquincho is used in folk medicine to improve memory. The cholinergic neurons of the basal forebrain, including those in the medial septum, and in the vertical limbs of the diagonal band of Broca and the nucleus basalis of Meynert, provide a major source of cholinergic enervation of the cortex and hippocampus. These neurons have also been shown to play an important role in learning and memory processes. Thus, the effects of this traditional Argentinean species were studied in relation to its activity on synaptic transmission in the hippocampus. The alkaloid extract obtained first by decoction of the aerial parts and by subsequent alkaline extraction, was purified by using a Sephadex LH 20 packed column. Electrophysiological experiments were developed with the purified extract (E(2)) on rat hippocampus slices, thus eliciting long-term potentiation (LTP). Results show a marked increase in the hippocampal synaptic plasticity. The threshold value for generation of LTP was 22 +/- 1.01 Hz on average for E(2), while for controls it was 86 +/- 0.92 Hz. All of these factors could explain the use of Huperzia saururus as a memory improver as is reported in the ethnomedicine.

Increased neuronal activity in locus coeruleus from adult rats undernourished at perinatal age: its reversal by desipramine.

The spontaneous activity of locus coeruleus (LC) noradrenergic neurons was assessed by single unit recording in adult recovered rats undernourished at perinatal age as compared with wellnourished animals. Locus coeruleus activity, measured by the firing rate of noradrenergic neurons and the number of spontaneously active cells/track was significantly higher in deprived rats than in controls. In addition, dose-response curves for the inhibitory LC activity of clonidine showed a shift to the right in deprived animals indicating a subsensitivity of alpha2-adrenergic autoreceptors. This fact suggests an alteration in the negative feedback mechanism mediated by somatodentritic alpha2 autoreceptors that modulate the activity of LC neurons, and may account for the behavioral alterations attributed to early undernutrition. Repeated desipramine (DMI) administration to deprived rats reduced LC activity to values comparable to controls, which were not affected after a similar treatment. These data extend to previous reports on long-lasting or permanent plastic changes in the CNS induced by early undernutrition, which may be reverted by pharmacological manipulations. In addition, these results support the hypothesis that alterations induced by early undernutrition are in the same direction as and resemble those described for patients with panic disorders. Furthermore, together with behavioral alterations and selective anxiolytic effect of DMI and other drugs with antipanic effects described in early malnourished rats, the present data support the proposal that perinatally deprived rats may be a useful model for screening drugs with potential antipanic activity.

Hippocampus and locus coeruleus activity on rats chronically treated with diazepam.

The neural mechanisms underlying benzodiazepine (BZD) dependence remain equivocal. The present studies tested the hypothesis that similar neural circuitry might be involved in the effects of chronic 7-chloro-1-methyl-5-phenyl-3H-1,4-benzodiazepine-2(1H)-one, diazepam (DZ, Roche), administration and withdrawal. The results of our study showed an increased hippocampal synaptic plasticity in slices from rats chronically treated with DZ (5 mg/kg/18 days), assessed as a decrease of the threshold in the stimulation rate for long-term potentiation (LTP) elicitation. Rats with the same schedule of DZ administration but without signs of withdrawal behaved similarly to vehicle-treated ones (VEH), in the threshold to induce LTP. Furthermore, the activity of locus coeruleus (LC) norepinephrine (NE) neurons in rats tested 24 h after the last DZ injection showed a significant increase. On the other hand, rats that after chronic DZ administration did not develop signs of withdrawal and exhibited a similar pattern of discharge on LC-NE nucleus compared with their controls. We conclude that chronic DZ administration enhances both hippocampal synaptic plasticity and activity of LC-NE neurons. This neural system could be the biological substrate underlying the behavioral alterations accompanying chronic DZ administration and withdrawal.

Effects of chronic risperidone on central noradrenergic transmission.

In the present work, we investigated the effects of chronic risperidone administration on the activity of locus coeruleus noradrenergic neurons. In addition, the effect of chronic risperidone administration on the basal level of norepinephrine in the prefrontal cortex was evaluated. Results of this research showed that chronic risperidone administration increased the activity of locus coeruleus noradrenergic neurons. The sensitivity of alpha(2)-adrenoceptors in the somatodendritic region of the locus coeruleus was assessed by using the ID(50) of clonidine. Results indicated that the firing rate of locus coeruleus noradrenergic neurons was the same in risperidone-treated rats and controls. Similarly, the ID(50) for (+/-)-2,5-dimetoxy-4-iodoamphetamine (DOI), an agonist of 5-HT(2) receptors which inhibits the activity of locus coeruleus neurons by acting on these receptors, did not show any differences between the firing rate of these neurons in risperidone treated rats and controls. Unlike controls, chronically treated rats showed a significant decrease in norepinephrine levels in the prefrontal cortex. The decreased release of norepinephrine following continuous risperidone administration could be explained by the sustained increase in locus coeruleus neuronal activity after chronic risperidone administration. This low norepinephrine level in the prefrontal cortex may contribute to the relief of certain negative schizophrenic symptoms and to the improvement of cognitive function.

Preexposure to drug administration context blocks the development of tolerance to sedative effects of diazepam.

The development of tolerance to benzodiazepine (BDZ) and other psychoactive agents such as morphine, alcohol, and barbiturates is thought to be a contingent or learning phenomenon. In a previous report, we demonstrated a positive correlation between the development of tolerance to the sedative effects of diazepam (DZ) and hippocampal synaptic plasticity. The results of the present work show that the development of tolerance to the hypolocomotor action of DZ (5 mg/kg) for 4 days and the associated increase in synaptic plasticity are context specific. Because animal preexposure to the drug administration context blocks both the tolerance sedative effects of DZ and the increased hippocampal synaptic plasticity, observed after 4 days of DZ administration, we propose the increased synaptic plasticity on hippocampal development as one of the biological substrates to the tolerance to DZ. Besides, the continuous administration of DZ did not induce a conditioning opponent response in these animals.

Estimating economic thresholds for pest control: an alternative procedure.

An alternative methodology to determine profit maximizing economic thresholds is developed and illustrated. An optimization problem based on the main biological and economic relations involved in determining a profit maximizing economic threshold is first advanced. From it, a more manageable model of 2 nonsimultaneous reduced-from equations is derived, which represents a simpler but conceptually and statistically sound alternative. The model recognizes that yields and pest control costs are a function of the economic threshold used. Higher (less strict) economic thresholds can result in lower yields and, therefore, a lower gross income from the sale of the product, but could also be less costly to maintain. The highest possible profits will be obtained by using the economic threshold that results in a maximum difference between gross income and pest control cost functions.

Permanent alteration of central noradrenergic system by prenatally administered amphetamine.

Amphetamine-induced psychosis is frequently associated with a chronic, high-dose, daily pattern of amphetamine exposure. In the present study we investigate the effects of prenatal exposure to amphetamine during the development of the central noradrenergic (NA) system in adult rats. Pregnant Wistar rats were given 4 mg/kg/day of d-amphetamine (AMPH), subcutaneously, from gestational day 8 to 21. No additional drug treatment was given to the animals until the beginning of the experiments, in adult, control and prenatally amphetamine treated rats. Since we study the electrophysiology and neurochemistry of the central NA system, we investigated the electric activity of locus coeruleus (LC) norepinephrine (NE) neurons and the levels of NE on prefrontal cortex. What we found, was a decreased number of spontaneously active cells in the LC nucleus with a lower pattern of discharge whereas, the basal levels of NE in the prefrontal cortex, was greatly increased. The increased cortical NE levels, observed in the present study may account for the proposed hyperactive NA system being responsible for some psychotic symptoms observed in paranoid schizophrenia. Besides, our results concerning the permanent alteration observed in the central NA system, in rats prenatally exposed to amphetamine, raise the possibility that this animal model may be useful to further study the neurobiologic alterations underlying certain clinical features involved in some psychosis such as schizophrenia.

Baclofen infused in rat hippocampal formation impairs spatial learning.

Recent studies show that baclofen, a selective GABA(B) agonist, impairs different kinds of learning. In the present study we investigated the effect of microinfused baclofen into the hippocampus of male Wistar rats, on the performance in the Morris water maze. Rats of 8-10 weeks of age were implanted with cannulae aimed bilaterally at the hippocampal formation. Baclofen (1 microl of 0.2 mM, 2.0 mM, and 20.0 mM) or sterilized saline was microinfused 1 h before each daily session (3 trials/session, 1 session/day) for 4 days. On the fifth day, the animals did not receive drug or saline injections and the retention of the location of the escape platform was tested in a 30 s free swim trial. Results from the free swim trial indicate that the doses of baclofen used during training affected the ability of the rats to swim to the target quadrant. Although no significant difference compared with the saline group was observed, the experimental rats showed a more generalized swim trajectory in the area of the target and both adjacent quadrants. Moreover, 1 microl of 20.0 mM baclofen also impaired the acquisition. We suggest that baclofen has an impairing action on spatial learning, although more studies should be conducted to reach a more precise conclusion.

The conditioned eyeblink response: a role for the GABA-B receptor?

In well-trained animals, infusion of the GABA-B agonist baclofen into the cerebellar interpositus nucleus and overlying cortex abolished the conditioned response (CR) with no effect on the unconditioned response (UR) with doses at or above 5.0 mM. Infusion of the GABA-B antagonist CGP 5584-5A alone had no effect on the CR or UR. However, administration of 5 mM baclofen soon after infusion of CGP 5584-5A (15 min) resulted in no reduction of percent CR and only partial reduction of CR amplitude. Naive animals given interpositus infusions of baclofen during training showed no learning, yet learned normally in postinfusion training. The distribution of (radiolabelled) baclofen was localized and remained within the cerebellum. The results presented here are consistent with a growing body of literature supporting the hypothesis that the memory trace for eyeblink conditioning is formed and stored in the cerebellum and may involve GABAergic mechanisms.

Rapid tolerance to benzodiazepine modifies rat hippocampal synaptic plasticity.

Glutamate antagonists to N-methyl-D-aspartate (NMDA) receptors blocks the development of "rapid' tolerance to the sedative action of benzodiazepines (BZDs). This kind of glutamate receptors is closely related to synaptic plasticity in different areas of the brain such as hippocampus. In the present investigation, we studied the synaptic plasticity in dentate gyrus of the hippocampus during the development of tolerance to the hypomotility action induced by diazepam (DZ). The results show an increased hippocampal synaptic plasticity in slices from rats treated with diazepam (5 mg/kg per day) during 4 days, assessed as a decrease of the threshold in the stimulation frequency for long-term potentiation (LTP) elicitation. Thus, a single dose of DZ does not change the ease of induction of LTP but does change locomotor behavior: multiple DZ doses change LTP but not locomotor behavior. Our results reveal a positive correlation between the synaptic plasticity and development of BZD tolerance to locomotor activity.

Equivalent performance in the water maze by rats with an inborn high or low learning capacity in a shuttle box paradigm.

The learning capacity of rats with an inborn high performance (HP) and low performance (LP) in an avoidance shuttle box paradigm, was evaluated in the Morris water maze. Escape latencies evaluated in HP and LP rats indicate that acquisition and retention of spatial information were not different from control animals. When a free swim trial was carried out, all groups showed a significant preference towards the target quadrant. Our results suggest that the altered hippocampal physiology described in HP and LP rats does not influence the performance of a spatial tasks such as the Morris water maze.

Effects of chronic desipramine administration on the locus coeruleus neuronal activity in the learned helplessness paradigm.

One week after inescapable shock (IS) exposure, animals showed an increased number of escape failures in the shuttlebox and a decreased noradrenergic (NA) transmission. The latter was assessed by electric activity of locus coeruleus (LC) neurons. Seven daily injections of desipramine (DMI) were effective in reducing the number of escapes failures in the shuttlebox, but such treatment did not modify the decreased electric activity of LC NA neurons observed 7 days after IS. These results are discussed in terms of the action of DMI on NA terminals in reversing the behavioral deficit induced by IS.

Phosphatidylserine increases hippocampal synaptic efficacy.

In the present study, the effects of phosphatidylserine (BC-PS) on hippocampal synaptic transmission were evaluated. Extracellular potentials evoked by low-frequency stimulation (0.2 Hz) of the perforant path (PP) were recorded from the granule cell layer of the dentate gyrus in 400 microns hippocampal slices. Slices were perfused with either BC-PS alone (10 microM) or BC-PS in combination with DL-2-amino-5-phosphonovaleric acid (APV, 20 microM), or after previous perfusion with dizocilpine (MK-801, 10 microM). BC-PS significantly potentiated PP-evoked responses (mean percent increase +/- SEM, 108 +/- 18%), an effect that was blocked by perfusion of MK-801, but not APV. The increase in hippocampal synaptic efficacy produced by BC-PS is discussed in terms of N-methyl-D-aspartate receptors (NMDA) and the associated channels.

Effect of acute ethanol exposure during pregnancy on dentate gyrus synaptic plasticity in 45-day-old rats.

Pregnant Wistar rats were treated during the eighth day of gestation (GD8) with two IP injections, spaced by an interval of 4 h, of either ethanol (2.9 g/kg in saline solution) or saline. At 45 days of age, rats prenatally exposed to alcohol showed an improved hippocampal synaptic plasticity in granule cells layer of dentate gyrus. This was assessed measuring the threshold to generate long-term potentiation (LTP) on hippocampal slices. We propose that this result might account for the good performance in some learning tasks observed in animals prenatally exposed to alcohol during short periods.

The learning capacity of high or low performance rats is related to the hippocampus NMDA receptors.

The hippocampal synaptic plasticity of rats with an inborn high (HP) or low (LP) learning capacity to perform in a shuttle box is closely related to their percentage of conditioned responses (Crs). HP rats show less sensitivity to the blocking effect of 2-aminophosphonopentanoic acid (AP5) on the generation of long-term potentiation (LTP) than do LP rats. Results described in the present report are indicative of an increased density of N-methyl-D-aspartate (NMDA) receptors in HP rats compared to control and LP rats. We postulate that the differential pharmacological sensitivity of LTP in these rats is a reflection of this biochemical difference. Also, from these results we suggest that the learning capacity may be related to the density of glutamate NMDA receptors of HP, LP and control rats.

Differences in hippocampal synaptic plasticity in rats with inborn high or low learning ability may be related to different sensitivity of aspartate receptors.

Rats with an inborn high (HP) or low (LP) learning capacity were used to study the sensitivity to the blocking effect of 2-amino-phosphonopentanoic acid (AP5; 10 and 20 microM) on long-term potentiation (LTP) produced in hippocampal slices by a 1-s tetanus at 200 Hz. The potential evoked by stimulation of the perforant path was recorded from the granule cell layer of the dentate gyrus in 400 microns slices perfused with standard Krebs' solution or the AP5. Under perfusion with 10 microM of AP5, in 100% of slices from HP rats, LTP generation was not blocked; when AP5 20 microM was used, in 85% of the cases LTP was not blocked. In 60% of slices from LP rats, AP5 10 microM and in 100% of the cases at 20 microM AP5 blocked LTP generation. These results are coherent with the hypothesis that the different inborn learning ability of HP and LP rats is related to the different population or sensitivity of N-methyl-D-aspartate (NMDA) receptors.