Excitability of single firing human motoneurones to single and repetitive stimulation (experiment and model)

The activity of single motoneurones of m. flexor carpi ulnaris (FCU) was investigated by recording their motor unit (MU) action potentials during weak and moderate voluntary muscle contractions. The MU firing rate range was 4.5-15 imp/s. The excitability of motoneurones was tested with a number of single stimuli eliciting a monosynaptic H-reflex of low amplitude. Two different indices were defined which relate to motoneuronal excitability: the response index--the ratio of the number of responses of a motoneurone to the total number of stimuli, and the response time--the time after the last background MU discharge at which motoneurone is ready to respond to the excitatory volley. Both the response index and the response time were determined for single motoneurones at different levels of background activity. In the lower range of firing rates, the response index for all motoneurones decreased when increasing the firing rate, but it remained constant in the higher rate range. This kind of response seems to be a typical motoneuronal response to the stimulation with single stimuli. The data on the response time were used to study the excitability of the same single motoneurones to computer simulated repetitive stimulation (stimulation rate 40-100 imp/s). In this case, the excitability of each motoneurone was determined as an increment of its firing rate in response to the stimulation. For the lower firing rate range, the excitability for all motoneurones also decreased when the firing rates increased whereas a variety of slopes was obtained in the higher rate range.(ABSTRACT TRUNCATED AT 250 WORDS)     

Specific ethanol withdrawal seizures in genetically selected mice

We are selectively breeding mice prone (WSP) and resistant (WSR) to ethanol withdrawal seizures assessed by handling induced convulsions (HIC). The possibility that differences between the lines in HIC scores are a result of differences in general CNS excitability not specific to ethanol withdrawal was examined. Using treatments which produce generalized seizures (electroconvulsive shock, strychnine, and flurothyl) and gamma amino-butyric acid (GABA) antagonists (picrotoxin, bicuculline, and pentylentetrazol), the ED50 for seizures was determined in the selected lines. In addition, the sensitivity of WSP and WSR mice to the anticonvulsant actions of ethanol against each treatment was determined. Neither the convulsant amperage 50 (CA50) for ECS nor the ED50 for any drug treatment differed for the selected lines. When ethanol (1.5 g/kg) was administered prior to ECS, there was a dramatic differential suppression of ECS in the lines: the CA50 of WSR mice was elevated 5-fold, whereas the CA50 of WSP mice increased only two fold. Ethanol pretreatment also elevated the ED50 for strychnine and flurothyl in WSR mice significantly more than WSP mice, but the line difference was smaller than for the anticonvulsant effect against ECS. The ED50s for the GABA antagonists were not different between the WSR and WSP lines after ethanol pretreatment. We conclude that genetic selection is producing lines of mice that differ specifically in the degree of seizure severity caused by withdrawal from ethanol physical dependence and not in generalized CNS excitability. An increased sensitivity to the anticonvulsant effects of ethanol against some convulsant treatments has appeared as a correlated response to selection in the WSR line.     

Abnormal distracter processing in adults with attention-deficit-hyperactivity disorder

Background

Subjects with Attention-Deficit Hyperactivity Disorder (ADHD) are overdistractible by stimuli out of the intended focus of attention. This control deficit could be due to primarily reduced attentional capacities or, e. g., to overshooting orienting to unexpected events. Here, we aimed at identifying disease-related abnormalities of novelty processing and, therefore, studied event-related potentials (ERP) to respective stimuli in adult ADHD patients compared to healthy subjects.

Methods

Fifteen unmedicated subjects with ADHD and fifteen matched controls engaged in a visual oddball task (OT) under simultaneous EEG recordings. A target stimulus, upon which a motor response was required, and non-target stimuli, which did not demand a specific reaction, were presented in random order. Target and most non-target stimuli were presented repeatedly, but some non-target stimuli occurred only once (‘novels’). These unique stimuli were either ‘relative novels’ with which a meaning could be associated, or ‘complete novels’, if no association was available.

Results

In frontal recordings, a positive component with a peak latency of some 400 ms became maximal after novels. In healthy subjects, this novelty-P3 (or ‘orienting response’) was of higher magnitude after complete than after relative novels, in contrast to the patients with an undifferentially high frontal responsivity. Instead, ADHD patients tended to smaller centro-parietal P3 responses after target signals and, on a behavioural level, responded slower than controls.

Conclusion

The results demonstrate abnormal novelty processing in adult subjects with ADHD. In controls, the ERP pattern indicates that allocation of meaning modulates the processing of new stimuli. However, in ADHD such a modulation was not prevalent. Instead, also familiar, only context-wise new stimuli were treated as complete novels. We propose that disturbed semantic processing of new stimuli resembles a mechanism for excessive orienting to commonly negligible stimuli in ADHD.     

Effect of Exogenous Cues on Covert Spatial Orienting in Deaf and Normal Hearing Individuals

Deaf individuals have been known to process visual stimuli better at the periphery compared to the normal hearing population. However, very few studies have examined attention orienting in the oculomotor domain in the deaf, particularly when targets appear at variable eccentricity. In this study, we examined if the visual perceptual processing advantage reported in the deaf people also modulates spatial attentional orienting with eye movement responses. We used a spatial cueing task with cued and uncued targets that appeared at two different eccentricities and explored attentional facilitation and inhibition. We elicited both a saccadic and a manual response. The deaf showed a higher cueing effect for the ocular responses than the normal hearing participants. However, there was no group difference for the manual responses. There was also higher facilitation at the periphery for both saccadic and manual responses, irrespective of groups. These results suggest that, owing to their superior visual processing ability, the deaf may orient attention faster to targets. We discuss the results in terms of previous studies on cueing and attentional orienting in deaf.     

Signals invisible to the collicular and magnocellular pathways can capture visual attention

The retinal projection to the superior colliculus is thought to be important both for stimulus-driven eye movements and for the involuntary capture of attention. It has further been argued that eye-movement planning and attentional orienting share common neural mechanisms. Electrophysiological studies have shown that the superior colliculus receives no direct projections from short-wave-sensitive cones (S cones), and, consistent with this, we found that irrelevant peripheral stimuli visible only to S cones did not produce the saccadic distractor effect produced by luminance stimuli. However, when involuntary orienting was tested in a Posner cueing task, the same S-cone stimuli had normal attentional effects, in that they accelerated or delayed responses to subsequent targets. We conclude that involuntary attentional shifts do not require signals in the direct collicular pathway, or indeed the magnocellular pathway, as our S-cone stimuli were invisible to this channel also.     

Substance P and the ethanol-evoked changes in the independent motivated behavioral reactions of rabbits

Ethanol (0.5 g/kg) administered intravenously led to alterations in central mechanisms of feeding and escape, elicited by threshold electrical stimulation either of lateral or of ventromedial hypothalamic centers of the rabbit. Subsequent intravenous injection of substance P (30 mcg/kg) restored the excitability of the ventromedial hypothalamus and facilitatory effects on this motivational center of the midbrain reticular formation. The restoration of both inhibitory influences of the dorsal hippocampus and facilitatory ones of the midbrain reticular formation on the excitability of the lateral hypothalamus was also observed after SP administration. Data obtained suggest that oligopeptides could be used to increase the tolerance to ethanol or to cure the negative acute effects of alcohol in motivated behaviours.     

Low-intensity repetitive transcranial magnetic stimulation decreases motor cortical excitability in humans.

Repetitive transcranial magnetic stimulation of the motor cortex (rTMS) can be used to modify motor cortical excitability in human subjects. At stimulus intensities near to or above resting motor threshold, low-frequency rTMS (approximately 1 Hz) decreases motor cortical excitability, whereas high-frequency rTMS (5-20 Hz) can increase excitability. We investigated the effect of 10 min of intermittent rTMS on motor cortical excitability in normal subjects at two frequencies (2 or 6 Hz). Three low intensities of stimulation (70, 80, and 90% of active motor threshold) and sham stimulation were used. The number of stimuli were matched between conditions. Motor cortical excitability was investigated by measurement of the motor-evoked potential (MEP) evoked by single magnetic stimuli in the relaxed first dorsal interosseus muscle. The intensity of the single stimuli was set to evoke baseline MEPs of approximately 1 mV in amplitude. Both 2- and 6-Hz stimulation, at 80% of active motor threshold, reduced the magnitude of MEPs for approximately 30 min (P < 0.05). MEPs returned to baseline values after a weak voluntary contraction. Stimulation at 70 and 90% of active motor threshold and sham stimulation did not induce a significant group effect on MEP magnitude. However, the intersubject response to rTMS at 90% of active motor threshold was highly variable, with some subjects showing significant MEP facilitation and others inhibition. These results suggest that, at low stimulus intensities, the intensity of stimulation may be as important as frequency in determining the effect of rTMS on motor cortical excitability.     

Face Orientation and Motion Differently Affect the Deployment of Visual Attention in Newborns and 4-Month-Old Infants

Orienting visual attention allows us to properly select relevant visual information from a noisy environment. Despite extensive investigation of the orienting of visual attention in infancy, it is unknown whether and how stimulus characteristics modulate the deployment of attention from birth to 4 months of age, a period in which the efficiency in orienting of attention improves dramatically. The aim of the present study was to compare 4-month-old infants’ and newborns’ ability to orient attention from central to peripheral stimuli that have the same or different attributes. In Experiment 1, all the stimuli were dynamic and the only attribute of the central and peripheral stimuli to be manipulated was face orientation. In Experiment 2, both face orientation and motion of the central and peripheral stimuli were contrasted. The number of valid trials and saccadic latency were measured at both ages. Our results demonstrated that the deployment of attention is mainly influenced by motion at birth, while it is also influenced by face orientation at 4-month of age. These findings provide insight into the development of the orienting visual attention in the first few months of life and suggest that maturation may be not the only factor that determines the developmental change in orienting visual attention from birth to 4 months.     

Increased CNS sensitivity to flurothyl as a measure of physical dependence in mice following morphine,phenobarbital, and ethanol treatment

Male C57BL/6 mice were administered either morphine, phenobarbital or ethanol in their drinking water in order to make them dependent. During withdrawal onset of myoclonus, clonus and tonus was evaluated with flurothyl, a convulsant inhalant. Morphine, phenobarbital and ethanol treated subjects displayed significantly lower latencies for myoclonic and clonic convulsive behavior when compared with their respective controls. The increased CNS excitability observed is characteristic of physical dependence and the flurothyl technique employed is discussed in light of its broad applicability to a number of agents characterized by their dependence producing properties.     

An attempt to confirm magnetic sensitivity in the pigeon,Columba livia

Summary An attempt was made to test the sensitivity of homing pigeons to weak magnetic variations of the order of the ones naturally occuring on earth. Pigeons were first subjected to a cardiac orienting reflex test to 50 magnetic stimuli and to 50 control stimuli presented alone and randomly interdigitated. They were then subjected to a differential nociceptive conditioning procedure using the same magnetic and control stimuli for 100 trials under each stimulus condition. Cardiac activity was used as an index of reactivity throughout the study. The tests were performed in uniform magnetic fields using 1 m diameter Helmholtz coils. Results indicate that the magnetic stimuli presentations did not evoke a cardiac orienting reflex when compared to the cardiac orienting response of control pigeons to a neutral luminous stimulus. Moreover, results from the conditioning tests indicate that the magnetic stimuli were not used by the pigeons as a cue presaging the forthcoming shock. It is concluded that, in the present experimental situation, homing pigeons did not respond to small changes in the ambiant magnetic field with changes in autonomic functioning. Results are discussed in the context of the inappropriateness of the stimuli and tests used to show magnetic sensitivity in birds.This research was carried out as part of a doctoral dissertation in the Département de Psychologie at the Université de Louvain (Belgique). The author is indebted to Professor G. Thinès, Director of the Centre de Psychologie Expérimentale et Comparée of the Université de Louvain for his guidance and encouragement as dissertation adviser. We would also like to express our appreciation to Dr. A. Vandenplass, director of the Institut Royal Metéorologique de Belgique and the Fédération Royale Colombophile de Belgique and to Professor J.L. Koenigsfeld from the University of Liège for their interest and cooperation in this research. Dr. Marco Citta and Louis Laurencelle gave computer assistance and Francois Labelle made the technical drawings. This research was supported by the Centre de Psychologie Expérimentale et Comparée and the Fédération Royale Colombophile de Belgique and made possible by a special leave of absence granted to the author by the Université du Québec à Montréal.     

Frequency-dependent excitability of "membrane" slow responses of Rabbit left atrial trabeculae in the presence of Ba2+ and high K+

Small trabeculae of rabbit left atrium immersed in TKBa solution (Tyrode with 10 mM K+ and 1 mM Ba2+) were used to study frequency dependence of "membrane" slow response excitability at long cycle lengths (greater than 1 s). In TKBa, stimuli generate graded, low- amplitude (2-15 mV) subliminal responses of variable long duration (up to 450 ms). A full all-or-none slow response is generated when a subliminal response depolarizes the membrane to about--35 mV. Subliminal response amplitude and rate of rise augment with stimulus intensity-duration product. For a fixed stimulus, the subliminal response is larger and faster at higher frequencies. Sudden changes in stimulus frequency or time course induce changes in subliminal response tha take four to eight cycles to attain steady state. For a fixed stimulus, slow response latency shortens progressively during the first few cycles after a sudden increase in frequency or when a rested preparation is excited (latency adaptation phenomenon, LAP). Slow response threshold stimulus requirements decrease during LAP (excitability hysteresis). The degree of excitability hysteresis is dependent on stimulation frequency and is more pronounced at higher frequencies. Frequency sensitivity of subliminal response (which causes frequency sensitivity of slow response excitability) is explained in terms of a transient state of enhancement set up by each stimulus. The enhanced state decays between stimuli with a half-time of approximately 4 s, thus allowing cumulative effects to become evident at rates above 0.1 Hz.     

The phases of visual cortex and hippocampal evoked potentials in rabbit reflect the orienting reaction in case of visual stimuli intensity changes

The oddball paradigm was applied in experiments with waking rabbits using rare (deviant) and frequent (standard) stimuli, which were similar in color but different in intensity, deviant ones being of lower intensity. In addition, the VEPs to the single deviants were averaged. Such single deviants (without standard stimuli) were given at the beginning and at the end of the stimulation. The positivity of cortical and hippocampal visual evoked potentials to deviant stimuli increased in comparison to responses to standards and single deviants. The VEP-peaks P1 and P2 in the visual cortex and the VEP P1, N1 and P2 peaks in hippocampus increased. The most prominent significant changes were demonstrated for cortical VEP P2 (P130) peak. It is suggested that the increase of positivity to oddball deviants is due to the orienting reflex arising in response to rare stimuli. The increase of P2-peak can be connected with the transfer of information signaling changes of light intensity. It was demonstrated that the most clear and contrast differences in the VEPs to deviants and standards took place for the case of minimal distinction in their intensities. This fact may reflect the orienting reactionto threshold stimuli.     

Hyperventilatory hypocapnia and muscle tonus

It has been established that hyperventilation hypocapnia inhibits the postural tone in both the unrespiratory and respiratory muscles. However, muscle excitability increases at the same time. As a result phasic as well as tonic reflexes in response to additional nervous stimuli are facilitated in the presence of hypocapnia.     

The Specificity Of Processes Of Motivational Conditioning In The Human Mind

The methodological principle of the objectification of needs, which in activity theory explains the ontological development of motivation (Leont'ev, 1975), is in need of concrete psychological development to ascertain what influences and mental processes give rise to such objectification. In terms of biological motivation, this question is made easier by the existence of a detailed system of data, accumulated in conditioning studies, concerning the acquisition of the capacity to activate a person by neutral stimuli. A psychological interpretation of these data purports to explain the fact that the conditioned response phenomenon indicates not only a redirecting of unconditioned responses toward new stimuli but also the genesis, in response to this stimulus, of subjective relations orienting the person toward influences relevant to his needs. Such an interpretation therefore helps to concretize the concept of the objectification of biological needs (Vilyunas, 1986. Pp. 154-74).     

Touch induces ATP release in Arabidopsis roots that is modulated by the heterotrimeric G-protein complex

Amongst the many stimuli orienting the growth of plant roots, of critical importance are the touch signals generated as roots explore the mechanically complex soil environment. However, the molecular mechanisms behind these sensory events remain poorly defined. We report an impaired obstacle-avoiding response of roots in Arabidopsis lacking a heterotrimeric G-protein. Obstacle avoidance may utilize a touch-induced release of ATP to the extracellular space. While sequential touch stimulation revealed a strong refractory period for ATP release in response to mechano-stimulation in wild-type plants, the refractory period in mutants was attenuated, resulting in extracellular ATP accumulation. We propose that ATP acts as an extracellular signal released by mechano-stimulation and that the G-protein complex is needed for fine-tuning this response.     

KCNQ Channels Show Conserved Ethanol Block and Function in Ethanol Behaviour

In humans, KCNQ2/3 channels form an M-current that regulates neuronal excitability, with mutations in these channels causing benign neonatal familial convulsions. The M-current is important in mechanisms of neural plasticity underlying associative memory and in the response to ethanol, with KCNQ controlling the release of dopamine after ethanol exposure. We show that dKCNQ is broadly expressed in the nervous system, with targeted reduction in neuronal KCNQ increasing neural excitability and KCNQ overexpression decreasing excitability and calcium signalling, consistent with KCNQ regulating the resting membrane potential and neural release as in mammalian neurons. We show that the single KCNQ channel in Drosophila (dKCNQ) has similar electrophysiological properties to neuronal KCNQ2/3, including conserved acute sensitivity to ethanol block, with the fly channel (IC₅₀ = 19.8 mM) being more sensitive than its mammalian ortholog (IC₅₀ = 42.1 mM). This suggests that the role of KCNQ in alcohol behaviour can be determined for the first time by using Drosophila. We present evidence that loss of KCNQ function in Drosophila increased sensitivity and tolerance to the sedative effects of ethanol. Acute activation of dopaminergic neurons by heat-activated TRP channel or KCNQ-RNAi expression produced ethanol hypersensitivity, suggesting that both act via a common mechanism involving membrane depolarisation and increased dopamine signalling leading to ethanol sedation.     

Effect of desglycine-arginine vasopressin on the excitability of the command neurons of the defensive reflex in the edible snail

Perfusion of the snail (Helix lucorum L.) CNS with DG-AVP (concentration 10(-6) M) in the course of low frequency intracellular stimulation (2-4-minute interval) of the defensive reflex command neurons led to an increase in the excitability. It was expressed both in the reduction of the spike generation latency, in the increased number of spikes in response to fixed stimuli, and in the activation of pacemaker potentials. If DG-AVP was added to the medium during endoneuronal habituation, there was no increase in the excitability. It is supposed that modification of the neuronal excitability may be caused by the DG-AVP effect on the pacemaker mechanism.     

Racial group membership is associated to gaze-mediated orienting in Italy

Viewing a face with averted gaze results in a spatial shift of attention in the corresponding direction, a phenomenon defined as gaze-mediated orienting. In the present paper, we investigated whether this effect is influenced by social factors. Across three experiments, White and Black participants were presented with faces of White and Black individuals. A modified spatial cueing paradigm was used in which a peripheral target stimulus requiring a discrimination response was preceded by a noninformative gaze cue. Results showed that Black participants shifted attention to the averted gaze of both ingroup and outgroup faces, whereas White participants selectively shifted attention only in response to individuals of their same group. Interestingly, the modulatory effect of social factors was context-dependent and emerged only when group membership was situationally salient to participants. It was hypothesized that differences in the relative social status of the two groups might account for the observed asymmetry between White and Black participants. A final experiment ruled out an alternative explanation based on differences in perceptual familiarity with the face stimuli. Overall, these findings strengthen the idea that gaze-mediated orienting is a socially-connoted phenomenon.     

Relation between warning stimuli and contingent negative variation in man

Seven right handed male students were submitted to standard and target paired auditory stimuli to determine the relationship between contingent negative variation (CNV) and the slow negative waves following non paired stimuli. The warning stimuli informed subjects whether or not the impending unconditional stimulus implied a motor response. Subjects were instructed to execute the motor task at less than one second after unconditional stimulus. They were informed that the standard warning stimulus would be followed by an additional stimulus which confirmed its detection. Recordings of standard warning stimulus condition showed a subsequent increase in CNV amplitude. This significant increase appeared to be related to an enhancement in the subject's expectation towards the additional stimulus. The lowered CNV voltage in target condition seemed to be linked to the instructions, which involved a motor preparation after the imperative stimuli occurrence. It is suggested that the CNV may represent not only a general anticipatory but also an orienting process related to the signal value of the warning stimulus.     

Wood Grain Pattern Formation: A Brief Review

In trees, new wood develops from a layer of stem cells called the vascular cambium. A subpopulation of cambial cells—the fusiform initials—are elongated and capable of coordinated reorientation in response to internal and external stimuli. Changes in the orientation of fusiform initials in turn leads to changes in the grain pattern of developing wood. This article reviews the phenomenon of cambial orientation, with an emphasis on a recent computer model that takes the plant hormone auxin as the orienting signal. New model results are presented that demonstrate the surprisingly complex grain patterns that can emerge from simple initial conditions, in qualitative agreement with similar patterns found in wood. Lastly, an alternative theory of wood grain pattern that takes mechanical stress as the orienting signal is critically evaluated.