The gap effect for eye and hand movements in double-step pointing

The existence of a temporal gap between the offset of a fixation target and the onset of a peripheral target generally reduces the saccadic and manual reaction time in response to the peripheral target. Using a double-step paradigm, the present experiment investigated whether a temporal gap between the extinction of the first target and the presentation of the second target can help in reducing the time to trigger the corrective eye movements and to correct the arm trajectory towards the final target position. A gap was introduced between the presentation of the initial target and a new unexpected goal-target during the movement. The results replicated the gap effect for the corrective saccade to the second target, but revealed an opposite effect for the correction of the reaching movements as the arm correction occurred later in the Gap than in the No-Gap conditions. These results suggest that the information available for the arm motor system to correct the trajectory in relation to the second target was different in the Gap and No-Gap conditions. In the No-Gap condition, the correction of reaching movements would be based on retinal errors between the first and the second targets whereas, in the Gap condition, the correction would be based on information derived from the corrective saccade-related signals to the second target.     

The contribution of coordinated eye and head movements in hand pointing accuracy

Summary The accuracy of pointing movements of the hand, directed at visual targets 10° to 40° from the midline, was measured in normal human subjects. No visual feedback from the moving hand was available to the subjects. The head could be either maintained stationary (head-fixed condition) or free to move (head-free condition) during the pointing movements. It was found that the error in pointing was reduced for all targets in the head-free condition. This reduction was more important for the more eccentric target (40°). Improvement in accuracy was observed without any significant change in either the latency or the duration of eye, head or hand movements. In the head-free condition, it was found that the head was displaced in the direction of the target by an amount representing no more than 2/3 of the target amplitude. The improvement in accuracy was not influenced by the amplitude of the head movement. A model is proposed which shows how coordinated eye and head movements could improve the encoding of target position.Work supported by INSERM-Unité 94     

Acquisition and performance in a rat sequential reaction time task is not affected by subtotal ventral striatal 6-OHDA lesions

Based on findings of experiments with humans, non-human primates and rodents, it is commonly accepted that dopaminergic basal ganglia processes play a crucial role in procedural and sequential learning. Primal evidence for this hypothesis came from serial reaction time tasks (SRTT) studies, demonstrating that healthy controls show increased reaction times when visual stimulus presentation switches from a previously learned sequence to random stimulus presentation. This so-called interference effect was reduced in patients with Parkinson's disease. Since ethical and methodical aspects limit neurobiological research in human subjects, we developed a rat version of the human SRTT, which can be used to study experimentally induced brain damage. In the present experiment we investigated the effects of bilateral 6-OHDA lesions of the ventral striatum on sequential learning. The lesions led to subtotal dopaminergic depletions in the ventral striatum (58–60%) and also minor depletions in the medial neostriatum (32–46%). These lesions impaired task acquisition only moderately and did not worsen sequential performance since lesion and control animals showed a comparable interference effect when the trained sequence was tested against random stimulus presentation or violated sequences. In contrast, in an earlier SRTT experiment with medial neostriatal dopaminergic lesions (58–66%), the lesion animals were clearly impaired in their sequential learning as compared to controls. Therefore, we assume that subtotal dopamine loss in the medial neostriatum, rather than the ventral striatum, has a substantial effect on sequential learning.     

The coordination of eye, head, and arm movements during rapid gaze orienting and arm pointing

This study aimed to investigate the coordination of multiple control actions involved in human horizontal gaze orienting or arm pointing to a common visual target. The subjects performed a visually triggered reaction time task in three conditions: (1) gaze orienting with a combined eye saccade and head rotation (EH), (2) arm pointing with gaze orienting by an eye saccade without head rotation (EA), and (3) arm pointing with gaze orienting by a combined eye saccade and head rotation (EHA). The subjects initiated eye movement first with nearly constant latencies across all tasks, followed by head movement in the EH task, by arm movement in the EA task, and by head and then arm movements in the EHA task. The differences of onset times between eye and head movements in the EH task, and between eye and arm movements in the EA task, were both preserved in the EHA task, leading to an eye-to-head-to-arm sequence. The onset latencies of eye and head in the EH task, eye and arm in the EA task, and eye, head and arm in the EHA task, were all positively correlated on a trial-by-trial basis. In the EHA task, however, the correlation coefficients of eye–head coupling and of eye–arm coupling were reduced and increased, respectively, compared to those estimated in the two-effector conditions (EH, EA). These results suggest that motor commands for different motor effectors are linked differently to achieve coordination in a task-dependent manner.     

Acute release of t-pa in rats and mice is inhibited by endotoxin and dexamethasone but is not affected by retinoic acid

To investigate the contribution of acute release of tissue type plasminogen activator (t-PA) on blood fibrinolytic activity, the ability to modulate the PAF-induced release of t-PA in perfused hindquarters of rats, mice, and hamsters was studied. Effects on t-PA release were compared with effects on ex vivo blood clot lysis. Animals were orally pretreated with dexamethasone (0.1–1 mg/kg) or retinoic acid (3 mg/kg) for a period of 5 days or intravenously with lipopolysaccharide (LPS: 0.03–50 μg/kg) for a period of 4 h. Maximum release of t-PA in response to PAF was 150, 40, and 6 U/kg in rats, mice, and hamsters, respectively, at concentrations of 2, 30, and 20 μM of PAF, respectively. Retinoic acid pretreatment had no effect on acute t-PA release in any of the species. Pretreatment with dexamethasone resulted in a dose-dependent decrease of the t-PA release in rats and mice to 25 ± 7% and 48 ± 6% (relative to vehicle treated animals), respectively at a dose of 1 mg/kg. LPS pretreatment resulted in about 45 % inhibition of t-PA release in both species at a dose of 50 μg/kg. No effects of dexamethasone or LPS were detected on acute release of t-PA in hamsters. In vivo acute release of t-PA in rats was inhibited by about 75% after dexamethasone pretreatment (I mg/kg) and by about 35% after LPS pretreatment (50 μg/kg). Pretreatment of rats with retinoic acid (3 mg/kg) had no effect on in vivo acute release of t-PA. LPS treatment resulted in complete inhibition of ex vivo measured blood clot lysis at doses of 0.3, 10, 0.1 μg/kg for rats, mice, and hamsters, respectively. Dexamethasone and retinoic acid affected the lysis rate of rat blood clots^1,2 but no effects on the lysis rates of murine or hamster blood clots were observed. It is concluded that in rats and mice but not in hamsters acute release of t-PA can be inhibited by pretreatment with dexamethasone or endotoxin. These effects do not parallel with effects on the rate of normal blood clot lysis.     

The frontal eye field is involved in spatial short-term memory but not in reflexive saccade inhibition

Physiological studies in monkeys have shown that the frontal eye field (FEF) is involved in the preparation and triggering of purposive saccades. However, several questions of FEF function remain unclear: the role of the FEF in visual short-term memory, its ability to update its spatial map and its role in reflexive saccade inhibition. We have addressed these issues in a patient with a small acute ischemic lesion whose location corresponded very accurately to the region of the left FEF according to the most recent cerebral blood flow studies. An initial study was conducted on days 7 and 8 after the stroke, i.e., before substantial recovery. A first group of paradigms (smooth pursuit, simple saccade tasks) was performed to assess FEF dysfunction. In a second group of paradigms, (1) visual short-term memory was tested by means of memory-guided saccade paradigms with short and long delays (1 and 7 s), (2) spatial updating abilities were tested by a double-step saccade task and two memory-guided saccade tasks in which the central fixation point was displaced during the memorization delay, and (3) reflexive saccade inhibition was tested by the antisaccade task. Results show that the FEF is involved in short-term memorization of the parameters of the forthcoming memory-guided saccade encoded in oculocentric coordinates. Normal results in the antisaccade task suggest that the FEF is not involved in reflexive saccade inhibition. Received: 26 January 1999 / Accepted: 3 June 1999     

Glucose oxidation in the ventromedial hypothalamus is not affected by insulin or ouabain but depressed by alloxan treatment

Summary Insulin is apparently not required for VMH glucose oxidation in vitro. Ouabain, an inhibitor of the Na-K pump ATPase, does not prevent VMH glucose oxidation in vitro. These data suggest (a) the VMH does not exhibit a cotransport phenomenon of glucose with the Na-K pump mechanism, and (b) glucose oxidation in the VMH is not insulin dependent. Alloxan-diabetes was induced to increase tissue insulin sensitivity. A comparison of glucose oxidation rates in alloxan-diabetic VMH tissue and normal VMH tissue, supplemented only with saline, indicated a highly significant (p < 0.001) depression of glucose oxidation in the alloxan-treated tissue. Cell membranes in the VMH are perhaps altered by alloxan.This work was supported by PHS/NIH Grant No. 5 SO5 RR07034, NIMH Grant No. R03 MH32916, in part by a grant from the Graduate College, Iowa State University, and in part by a gift from Houston Endowment Inc     

The relationship between aortic baroreceptor activity and arterial pressure is not monotonic

Previous reports indicate that when aortic pressure (AP) falls below the threshold (P _th) for baroreceptor sensitivity, activity in the aortic depressor nerve (ADN) may increase. To quantify and explain this anomalous behaviour, we analysed curves describing the relationship of baroreceptor fibre activity in rabbit left ADN to AP. Data were obtained in anaesthetised New Zealand White rabbits. Occlusion and release of cuffs around the inferior vena cava and descending aorta generated AP ramps (25–140 mmHg). Response curves were obtained for 173 fibres in 26 animals. Thirty percent of curves had a nadir (J-shaped curve), and in 40% activity was always present. In fibres showing activity below P _th, firing was predominantly diastolic, switching to systolic firing at P _th. The unusual behaviour of a substantial fraction of aortic baroreceptors below P _th accounts for the J-shaped response curve of the whole ADN. We suggest that fibres that fire during diastole at pressures below P _th may have sensory endings close to the origin of the left subclavian artery. As a consequence of this anatomical location, low pressures can impose strain on these receptors, which is then relieved by the systolic pulse.     

Intraventricular injection of NGF, but not BDNF, induces rapid motor activation that is inhibited by nicotinic receptor antagonists

 The acute and subacute effects of intracerebroventricularly (ICV) administered nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF) on locomotor activity were evaluated in awake adult rats. Immediately after ICV injection through an implanted cannula, locomotor activity was measured by a computerized system using infrared photocells, which allowed us to record locomotion, motility, and rearing simultaneously. A single dose of 5 μg mouse β-NGF produced significant increases in horizontal ambulatory components of locomotor activity (locomotion and motility), but not vertical movement (rearing) 30–45 min after ICV administration. These increases lasted for at least 3–4 h. Systemic injection of 2.0 mg/kg mecamylamine, a central nicotinic receptor antagonist, inhibited the hyperactivity induced by NGF. Systemic injection of 0.5 mg/kg scopolamine, a muscarinic receptor antagonist, did not interfere with the NGF effects. Thus, while scopolamine induced marked increases in all three measures of behavior in both NGF and cytochrome-c-treated animals, locomotion and motility remained significantly higher in the NGF group. Immunohistochemistry demonstrated that NGF diffused readily from the ventricular space into brain parenchyma on the injected side and could be visualized 1 h after ICV injection. These results suggest that ICV administration of NGF increases locomotor activity by inducing acetylcholine release, and that nicotinic receptors are involved in the hyperactivity induced by NGF. ICV administration of 5 μg recombinant human BDNF had no significant effect on locomotor activity during the 0- to 4-h period after ICV injection. However, it produced significant decreases in locomotion, motility, and rearing 24–26 h later. Hence ICV administration of BDNF has entirely different effects on animal behavior from those evoked by NGF. While NGF elicits increases in ambulatory behavior within hours, BDNF causes delayed decreases in ambulatory behavior. Received: 21 October 1996 / Accepted: 20 March 1997     

Feline left ventricular oxygen consumption is not affected by volume expansion,ejection or redevelopment of pressure during relaxation

We studied the dependency of myocardial oxygen consumption on the mechanical events during left ventricular relaxation in isolated supported cat hearts. The volume of the left ventricle was controlled by means of a balloon connected to a membrane pump. Oxygen consumption ( \(M\dot VO_2 \) in cm³·min^?1·100 g^?1) for three protocols (PROT) performed at peak isovolumic pressure, was studied: (1) rapid ejection to zero pressure, (2) partial rapid ejection followed by redevelopment of pressure, (3) volume expansion during relaxation, and compared with oxygen consumption of isovolumic (ISOV) beats. We found (mean±SD):

Chloroquine-induced inhibition of the production of TNF, but not of IL-6, is affected by disruption of iron metabolism.

There is now considerable evidence that cerebral malaria may be related to the over-production of tumour necrosis factor (TNF). Nevertheless, our knowledge is very poor concerning the biological events which lead up to this TNF over-production. Furthermore, interleukin-6 (IL-6) is produced in large amounts during malaria infection and seems to have inhibitory action on TNF production. Anti-malarial drugs were investigated for their ability to interfere with TNF and IL-6 secretion by human non-immune macrophages stimulated by lipopolysaccharides (LPS) or Plasmodium falciparum culture supernatant. Macrophages were pretreated with chloroquine, quinine, proguanil, mefloquine or halofantrine before stimulation. TNF and IL-6 production were suppressed in a dose-dependent manner when macrophages were treated with chloroquine, but not with other anti-malarial drugs. Considering that chloroquine probably acts via lysosomotropic mechanisms, and that iron metabolism may interfere with the non-specific immune response, we focused our attention on these biochemical events in order to investigate the mechanisms by which chloroquine inhibits cytokine production. Our results demonstrated that chloroquine-induced inhibition of TNF and IL-6 production is not mediated through a lysosomotropic mechanism, and that chloroquine probably acts on TNF secretion by disrupting iron homeostasis. Inhibition of IL-6 production seems not to be mediated through these pathways. These observations suggest that chloroquine may help to prevent cerebral malaria whatever the drug sensitivity of the parasite strain, and may provide new tools for an anti-disease therapy regardless of the emergence of parasite multi-drug resistance.     

Acyl-coenzyme A binding protein expression is fibre-type specific in rat skeletal muscle but not affected by moderate endurance training

The metabolic active form of free fatty acids, long-chain acyl-coenzyme A (lc-acyl-CoA), binds to its 10-kDa binding protein with high affinity. In the present study, we investigated the content of lc-acyl-CoA binding protein (ACBP) in different skeletal muscle fibre types. Soleus had the highest expression of ACBP (0.33+/-0.02 microg mg protein(-1)) and the content was as high as in heart muscle. The content in mixed gastrocnemius (0.27+/-0.02 microg mg protein(-1)), extensor digitorum longus (0.21+/-0.01 microg mg protein(-1)) and white gastrocnemius (0.16+/-0.01 microg mg protein(-1)) were lower than in soleus and differed from each other ( P<0.05). The ACBP content correlated positively with the fraction of myosin heavy chain I in the skeletal muscles (Spearman rank correlation rho=0.90; P<0.0001), and negatively with the myosin heavy chain IIB fraction ( rho=-0.92; P<0.0001). The content of ACBP also correlated with 3-hydroxy-acyl-CoA dehydrogenase (HAD) and citrate synthase (CS). Five weeks of endurance training increased HAD and CS activities in soleus and mixed gastrocnemius but did not affect the ACBP content. These findings demonstrate that ACBP expression is fibre-type specific in skeletal muscles and correlates with beta-oxidative potential. Training-induced increase in oxidative capacity was not paralleled by an increase in ACBP content.     

The cerebral metabolic ratio is not affected by oxygen availability during maximal exercise in humans

Intense exercise decreases the cerebral metabolic ratio of O(2) to carbohydrates (glucose + (1/2) lactate) and the cerebral lactate uptake depends on its arterial concentration, but whether these variables are influenced by O(2) availability is not known. In six males, maximal ergometer rowing increased the arterial lactate to 21.4 +/- 0.8 mm (mean +/- s.e.m.) and arterial-jugular venous (a-v) difference from -0.03 +/- 0.01 mm at rest to 2.52 +/- 0.03 mm (P < 0.05). Arterial glucose was raised to 8.5 +/- 0.5 mm and its a-v difference increased from 1.03 +/- 0.01 to 1.86 +/- 0.02 mm (P < 0.05) in the immediate recovery. During exercise, the cerebral metabolic ratio decreased from 5.67 +/- 0.52 at rest to 1.70 +/- 0.23 (P < 0.05) and remained low in the early recovery. Arterial haemoglobin O(2) saturation was 92.5 +/- 0.2% during exercise with room air, and it reached 87.6 +/- 1.0% and 98.9 +/- 0.2% during exercise with an inspired O(2) fraction of 0.17 and 0.30, respectively. Whilst the increase in a-v lactate difference was attenuated by manipulation of cerebral O(2) availability, the cerebral metabolic ratio was not affected significantly. During maximal rowing, the cerebral metabolic ratio reaches the lowest value with no effect by a moderate change in the arterial O(2) content. These findings suggest that intense whole body exercise is associated with marked imbalance in the cerebral metabolic substrate preferences independent of oxygen availability.