T-pattern detection and analysis for the discovery of hidden features of behaviour.

BACKGROUND: The behaviour of all living beings consists of hidden patterns in time; consequently, its nature and its underlying dynamics are intrinsically difficult to be perceived and detected by the unaided observer. METHOD: Such a scientific challenge calls for improved means of detection, data handling and analysis. By using a powerful and versatile technique known as T-pattern detection and analysis (TPA) it is possible to unveil hidden relationships among the behavioural events in time. RESULTS: TPA is demonstrated to be a solid and versatile tool to study the deep structure of behaviour in different experimental contexts, both in human and non human subjects. CONCLUSION: This review deepens and extends contents recently published by adding new concepts and examples concerning the applications of TPA in the study of behaviour both in human and non-human subjects.

Discovery of recurring behavioural sequences in Wistar rat social activity: Possible support to studies on Autism Spectrum Disorders.

This study was undertaken to investigate whether, in rat interactive activities, recurring sequences of behavioural events might be identified and how and to what extent each component of the pair is involved. To this aim, the multivariate temporal-pattern (t-pattern) analysis was applied to the social interactions of 9 pairs of male Wistar rats tested in open field. Interactive activities were classified into intra- and inter-subjects. Quantitative evaluations showed that intra-subject behavioural elements represented 62.37% and inter-subject ones 37.63% of the comprehensive behaviour. T-pattern analysis revealed the presence of 221 different t-patterns organized in four different categories: containing exclusively inter-subject elements; containing both inter- and intra-subject elements; consisting of rat 1 and rat 2 intra-subject elements and, finally, consisting of intra-subject elements carried out by one of the two subjects. Results show that the activity of two interacting Wistar rats is structured on the basis of several recurring temporal sequences. Moreover, social interactions appear to be expressed also by t-patterns where the behavioural elements are carried out by animals seemingly not interacting. A support of t-pattern analysis to studies on Autism Spectrum Disorders is proposed.

Temporal patterns of rat behaviour in the central platform of the elevated plus maze. Comparative analysis between male subjects of strains with different basal levels of emotionality.

We have analyzed the temporal patterns of behaviour of male rats of the Wistar and DA/Han strains on the central platform of the elevated plus maze. The ethogram encompassed 10 behavioural elements. Durations, frequencies and latencies showed quantitative differences as to walking and sniffing activities. Wistar rats displayed significantly lower latency and significantly higher durations and frequencies of walking activities. DA/Han rats showed a significant increase of sniffing duration. In addition, DA/Han rats showed a significantly higher amount of time spent in the central platform. Multivariate T-pattern analysis revealed differences in the temporal organization of behaviour of the two rat strains. DA/Han rats showed (a) higher behavioural complexity and variability and (b) a significantly higher mean number of T-patterns than Wistar rats. Taken together, T-pattern analysis of behaviour in the centre of the elevated plus maze can noticeably improve the detection of subtle features of anxiety related behaviour. We suggest that T-pattern analysis could be used as sensitive tool to test the action of anxiolytic and anxiogenic manipulations.

Role of the cardio-pulmonary exercise test and six-minute walking test in the evaluation of exercise performance in patients with late-onset Pompe disease.

In patients with late-onset Pompe disease, we explored the role of the Cardiopulmonary Exercise Test (CPET) and the Six-Minute Walking Test (6MWT) in the assessment of exercise capacity and in the evaluation of the effects of enzyme replacement therapy (ERT). Eight patients affected by late-onset Pompe disease, followed up at the Centre for Neuromuscular Diseases and treated with ERT, underwent a baseline evaluation with a spirometry, a CPET and a 6MWT. Four of them were restudied after 36 months of treatment. Three patients showed a reduction in exercise capacity as evaluated by peak oxygen uptake (VO2) measured at the CPET and Distance Walked (DW) measured at the 6MWT (median % predicted: 67.1 [range 54.3-99.6] and 67.3 [56.6-82.6], respectively). Cardiac and respiratory limitations revealed by the CPET were correlated to peak VO2, but not to the DW. Nevertheless, percent of predicted values of peak VO2 and DW were strongly correlated (rho = 0.85, p = 0.006), and close to identity. In the longitudinal evaluation forced vital capacity decreased, while peak VO2 and DW showed a trend to a parallel improvement. We concluded that although only the CPET revealed causes of exercise limitation, which partially differed among patients, CPET and 6MWT showed a similar overall degree of exercise impairment. That held true in the longitudinal assessment during ERT, where both tests demonstrated similar small improvements, occurring despite deterioration in forced vital capacity.

T-pattern analysis for the study of temporal structure of animal and human behavior: a comprehensive review.

A basic tenet in the realm of modern behavioral sciences is that behavior consists of patterns in time. For this reason, investigations of behavior deal with sequences that are not easily perceivable by the unaided observer. This problem calls for improved means of detection, data handling and analysis. This review focuses on the analysis of the temporal structure of behavior carried out by means of a multivariate approach known as T-pattern analysis. Using this technique, recurring sequences of behavioral events, usually hard to detect, can be unveiled and carefully described. T-pattern analysis has been successfully applied in the study of various aspects of human or animal behavior such as behavioral modifications in neuro-psychiatric diseases, route-tracing stereotypy in mice, interaction between human subjects and animal or artificial agents, hormonal-behavioral interactions, patterns of behavior associated with emesis and, in our laboratories, exploration and anxiety-related behaviors in rodents. After describing the theory and concepts of T-pattern analysis, this review will focus on the application of the analysis to the study of the temporal characteristics of behavior in different species from rodents to human beings. This work could represent a useful background for researchers who intend to employ such a refined multivariate approach to the study of behavior.

Soluble interleukin-2 receptor release defect in vitro in elderly subjects.

The evidence from several studies indicates that as individuals age, they may display immune dysfunctions, mostly T cell dysfunctions. Recently, a soluble form of the receptor for interleukin-2 (IL-2) (sIL-2R) has been demonstrated in human sera and in vitro stimulated culture supernatants from human T lymphocytes. In the present paper, we report in vitro sIL-2R production from peripheral blood mononuclear cells in elderly subjects. The results show that no difference exists for unstimulated cultures, whereas after mitogen stimulation the elderly subjects showed the lowest values compared with young ones. These findings suggest that sIL-2R may provide a new tool for the study of T lymphocyte dysfunctions in old age.

The effect of age on mitogen responsive T cell precursors in human beings is completely restored by interleukin-2.

It is well known that the function of T lymphocytes is significantly impaired by advancing age. In the present study, attempts have been made to further characterize the T cell impairment of elderly subjects. Thus, we have performed limiting dilution microculture analysis to evaluate the precursor frequency of T lymphocytes responding to a mitogenic stimulus in old and young subjects. Furthermore we have evaluated the activity of recombinant interleukin-2 (rIL-2) on these cells. The results demonstrate that in older subjects the frequency of these precursors is significantly decreased. The in vitro treatment with rIL-2 increased the frequency of mitogen responsive T lymphocyte precursors in both groups so that the difference between the two groups was not significant. Thus present results extend the findings demonstrating that older subjects display an impairment of T cell functions and that IL-2 treatment may correct these alterations. In particular, they confirm the hypothesis that age-associated functional changes are more likely due to diminished numbers of reactive cells, than to a decline in the activity of all cells.

Stimulation of the ventral tegmental area (A10 region) enhances the hypothalamic attack behavior in the cat.

The influence of the A10 region of the ventral tegmental area (VTA) on the quiet biting attack evoked by stimulation of the lateral hypothalamic nucleus (LH) was studied. The latency of the biting was considered as reference value and measured with stop-watches; it remained constant when hypothalamic stimulation was performed with the same parameters. Simultaneous activation of the A10 neuron group induced a facilitation of the aggression in the form of a decrease in the biting latency or a display of the attack pattern when LH was stimulated with parameters below the threshold for biting appearance. The facilitatory effect of the A10 neurons of the VTA is discussed.

Circling behavior: ethological analysis and functional considerations.

Head-turning and circling movements evoked by substantia nigra (pars compacta) (SNpc) stimulation have been ethologically analyzed in order to attribute a functional meaning to these lateralization processes. It has been shown that these motor acts, separated by a constant interval, may be considered a fixed action pattern. The duration of the single acts depends on the SNpc stimulation parameters: the increase in the stimulus strength produces an increase in the number of turns but does not induce the disappearance of the orientation movement. The body movement is always preceded by the head-movement. Haloperidol administration induces a dose-related increase of the orientation component of the motor pattern. These data together with others in the literature suggest the participation of the SNpc in the mechanism of shift in the focus of attention from one point to another in the contralateral surrounding environment.

The influence of dopaminergic A10 neurons on the motor pattern evoked by substantia nigra (pars compacta) stimulation.

The influence of the mesolimbic-mesocortical dopaminergic (DA) system on the motor pattern evoked by substantia nigra pars compacta (SNpc) stimulation was studied. Electrical stimulation of the A10 group of neurons caused an inhibitory effect preferentially directed towards the orientation movement. Sulpiride administration at low dosages (50 mg/kg i.p.) did not modify this movement at the basal condition, but abolished the increase of its duration induced by ventral tegmental area (VTA) co-stimulation. Mesolimbic activation opposes the effects of SNpc stimulation, restraining the animal in its antero-posterior axis by means of orientation movement inhibition. The results suggest a role of the DA mesolimbic-mesocortical system in the maintenance of focused attention.

Inhibitory effect of the ventral tegmental A10 region on the hypothalamic defence reaction: evidence for a possible dopaminergic mediation.

The influence of A10 region neurons of the ventral tegmental area (VTA) on the defence reaction evoked by stimulation of the ventromedial hypothalamic nucleus (VMH) was studied in the cat. The latency of the hissing in the defence reaction increased when the VTA was stimulated both ipsi- and contralaterally. A sulpiride (50mg/kg i.p.) injection totally abolished the VTA-provoked increase of the hissing latency without affecting the basal response.

Influence of ventral tegmental area (A10 region) on flight behaviour elicited by hypothalamic stimulation in the cat.

The influence of the ventral tegmental area (VTA) (dopaminergic A10 group neurons) on flight behaviour, induced by hypothalamic stimulation, was studied in the cat. Co-stimulation of hypothalamus and VTA (ipsi- or contralateral) induced an increase of the flight latency. Slow-motion analysis of flight behaviour showed that this increase was due to the augmentation of the fixation latency (FL) whereas the upright latency (UL) was not modified. Sulpiride injection (50 mg/kg i.p.) provoked the disappearance of VTA effect without affecting the basal behavioural sequence. The results show that DA A10 group neurons increase the attentive component of the flight reaction, suggesting a possible influence of the DA A10 system on the mechanisms modulating focused attention in the animal.

Accumbens microinjection of LY 171555 and sulpiride: effects on circling behaviour, in the rat.

In rats with unilateral 6-hydroxydopamine lesions of the substantia nigra (pars compacta) and amphetamine i.p. some parameters of the rotational activity, following intra-accumbens microinjection of D2 agonist (LY 171555) and antagonist (sulpiride), have been analyzed. An increase in the number of turns was observed with LY 171555, whereas sulpiride determined a decrease. The type of circling was also analyzed: D2 agonist induced a very close turn around the central axis of the animal and D2 antagonist a close turn in the centre of the cage. Data were compared with control condition, which exhibited a large turn around the walls of the cage. The results show that pharmacological manipulation of nucleus accumbens influences rotational behaviour with a specific role for D2 receptors.

The control exerted by the substantia nigra on the quiet biting attack elicited by hypothalamic stimulation in the cat.

The effects of substantia nigra (SN) (pars compacta) stimulation on the quiet biting attack evoked by hypothalamic activation in the cat were studied. The measure of the aggressive behavior was the latency of the biting which did not greatly change from one animal to another when hypothalamic stimulation was performed with the same parameters. Concurrent activation of the SN determined an inhibitory effect on the studied behavior in the form of an increase in the biting latency or loss of the attack pattern. The inhibitory role of the SN on predatory attack behavior is discussed.

Electrophysiological relationship between claustrum and contralateral area 4 and 6 pyramidal tract neurons.

The connections between the claustrum and the contralateral motor areas were electrophysiologically investigated in cats under chloralose anesthesia. The extracellular unitary activity of 81 pyramidal tract neurons (PTNs) was recorded; 22 PTNs were inhibited by activation of the contralateral claustrum; inhibition was preceded by an early activation of 4 out of the 22 inhibited PTNs. Section of the corpus callosum abolished the contralateral claustrum effect, while the action of the ipsilateral homologous structure persisted.

Effect of claustrum stimulation on neurons of the contralateral medial oculomotor area, in the cat.

In chloralose-anaesthetized cats, the extracellular spontaneous unitary activity was recorded from 157 neurons, located in the medial oculomotor area. 98 units were identified as projecting onto the superior colliculus. Electrical stimulations of the contralateral claustrum provoked, on 13 of these cells, an excitatory effect, lasting 10-35 ms and appearing with a latency of 20-50 ms. Full length section of the corpus callosum totally abolished the contralateral claustrum effect. The results suggest that in the cat, the claustrum may have a role in the bilateral control of the visuo-motor performance.

Effect of claustrum activation on the spontaneous unitary activity of frontal eye field neurons in the cat.

The influence of claustrum stimulation on spontaneous unitary activity of the ipsilateral frontal oculomotor area was analyzed in anesthetized cats. Sixty-five neurons were isolated, 37 of which (57%) were identified as projecting to the superior colliculus; on 12 of these last units (32%), electrical activation of the dorsal claustrum provoked an excitatory effect, which appeared after a latency of 5-15 ms and lasted 10-25 ms. These data could suggest the involvement of the claustrum in the visuomotor coordination function.

Functional relationship between claustrum and pyramidal tract neurons, in the cat.

Electrophysiological relationships between the claustrum and the motor cortex were studied in cats preliminarily anesthetized with ketamine and then with chloralose. Single shock electrical activation of the claustrum induced a decrease of the spontaneous unitary activity of the pyramidal tract neurons (PTNs) both in area 4 and in area 6. Eighty percent of the total number of PTNs was inhibited whereas the remaining 20% was unaffected. The inhibitory effect lasted about 200 msec and appeared about 19 msec after claustrum activation. The results show a functional linkage between the claustrum and the efferent cells of the motor cortex. This relationship suggests the hypothesis that the claustrum, a multisensory structure, may be involved in motor activity integration.

Modifications of head turning and circling movement following sulpiride microinjections into nucleus accumbens in the rat.

The aim of this study was to determine whether a relationship exists between nucleus accumbens D2 receptors, circling behavior, and its first stage, the head turning. Rats were unilaterally lesioned in the substantia nigra with 6-hydroxydopamine and afterward treated with d-amphetamine IP following bilateral intraaccumbens microinjections (1, 5, 10 micrograms/0.5 microliters) of sulpiride, a D2 receptor antagonist. Computer-assisted video analysis allowed the study of some parameters (number of turns, type of turn, head turning duration, degree and speed) characterizing rotatory activity. Sulpiride microinfusion resulted in a dose-dependent decrease of the number of turns and head rotation speed and in a dose-dependent increase of head-turning duration. Two turn types were observed in relation to the animal's position: a large head-to-tail position with a short-diameter turn type following sulpiride microinjection, and a close head-to-tail position in relation to a wide diameter turn type in the control condition (saline). The results show a relationship between head turning parameters, circling behavior, and D2 receptors in nucleus accumbens, which may be also involved in the regulation of some mechanisms related to sensory-motor integration in the rat.