Hypocretin/orexin in addiction: a mediator of stress-induced reinstatement of cocaine-seeking behaviour

The importance of the lateral hypothalamus in the pursuit of reward has long been recognized. However, the hypothalamic neuronal network involved in the regulation of reward still remains partially unknown. Hypocretins (aka orexins) are neuropeptides synthesized by a few thousand neurons restricted to the lateral hypothalamus and the perifornical area. Compelling evidence indicates that hypocretin neurons receive inputs from sensory and limbic systems and drive hyper-arousal possibly through modulation of stress responses. Major advances have been made in the elucidation of the hypocretin involvement in the regulation of arousal, stress, motivation, and reward seeking, without clearly defining the role of hypocretins in addictionrelated behaviors. We have recently gathered substantial evidence that points to a previously unidentified role for hypocretin-1 in driving relapse for cocaine seeking through activation of brain stress pathways. Meanwhile, several authors published concordant observations rather suggesting a direct activation of the mesolimbic dopamine system. In particular, hypocretin-1 has been shown to be critically involved in cocaine sensitization through the recruitment of NMDA receptors in the ventral tegmental area. Overall, on can conclude from recent findings that activation of hypocretin/orexin neurons plays a critical role in the development of the addiction process, either by contributing to brain sensitization (which is thought to lead to the unmanageable desire for drug intake) or by modulating the brain reward system that, in coordination with brain stress systems, leads to a vulnerable state that may facilitate relapse for drug seeking behavior.

Using music as a signal for biofeedback

Studies on the potential benefits of conveying biofeedback stimulus using a musical signal have appeared in recent years with the intent of harnessing the strong effects that music listening may have on subjects. While results are encouraging, the fundamental question has yet to be addressed, of how combined music and biofeedback compares to the already established use of either of these elements separately. This experiment, involving young adults (N = 24), compared the effectiveness at modulating participants' states of physiological arousal of each of the following conditions: A) listening to pre-recorded music, B) sonification biofeedback of the heart rate, and C) an algorithmically modulated musical feedback signal conveying the subject's heart rate. Our hypothesis was that each of the conditions (A), (B) and (C) would differ from the other two in the extent to which it enables participants to increase and decrease their state of physiological arousal, with (C) being more effective than (B), and both more than (A). Several physiological measures and qualitative responses were recorded and analyzed. Results show that using musical biofeedback allowed participants to modulate their state of physiological arousal at least equally well as sonification biofeedback, and much better than just listening to music, as reflected in their heart rate measurements, controlling for respiration-rate. Our findings indicate that the known effects of music in modulating arousal can therefore be beneficially harnessed when designing a biofeedback protocol.

Atmung, Aufmerksamkeit und Ablenkung als Funktion emotionaler Stimuli: Ablenkung, Atmung, Aufmerksamkeit, Emotion, Erregung, Valenz

Mittels Bilder, Musikstücken und Geräuschen induzierten wir Emotionen und gingen einerseits der Frage nach, wie emotionale Bewertung und physiologische Vorgänge, insbesondere die Atmung, miteinander verknüpft sind. Andererseits untersuchten wir mit Geruchsexpositionen während einer Mehrfachverrichtung, welche Rolle die Geruchs-Valenz bei der Arbeitsablenkung spielt. Unsere Versuche zeigten, dass die Atmungsantworten auf induzierte Emotionen in einem gewissen Rahmen dem Dimensionsmodell von Valenz und Arousal folgten, insbesondere bildeten sie die induzierte Erregung konsistent ab. Auch das Aufmerksamkeits-Engagement hing von der emotionalen Bedeutung des Stimulus ab, da nur die negativ attribuierten Gerüche eine Leistungsminderung in der Mehrfachverrichtung auslösten. [Autoren]

Proxemics with multiple dynamic characters in an immersive virtual environment

An experiment was carried out to examine the impact on electrodermal activity of people when approached by groups of one or four virtual characters at varying distances. It was premised on the basis of proxemics theory that the closer the approach of the virtual characters to the participant, the greater the level of physiological arousal. Physiological arousal was measured by the number of skin conductance responses within a short time period after the approach, and the maximum change in skin conductance level 5 s after the approach. The virtual characters were each either female or a cylinder of human size, and one or four characters approached each subject a total of 12 times. Twelve male subjects were recruited for the experiment. The results suggest that the number of skin conductance responses after the approach and the change in skin conductance level increased the closer the virtual characters approached toward the participants. Moreover, these response variables were inversely correlated with the number of visits, showing a typical adaptation effect. There was some evidence to suggest that the number of characters who simultaneously approached (one or four) was positively associated with the responses. Surprisingly there was no evidence of a difference in response between the humanoid characters and cylinders on the basis of this physiological data. It is suggested that the similarity in this quantitative arousal response to virtual characters and virtual objects might mask a profound difference in qualitative response, an interpretation supported by questionnaire and interview results. Overall the experiment supported the premise that people exhibit heightened physiological arousal the closer they are approached by virtual characters.

Proxemics with multiple dynamic characters in an immersive virtual environment

An experiment was carried out to examine the impact on electrodermal activity of people when approached by groups of one or four virtual characters at varying distances. It was premised on the basis of proxemics theory that the closer the approach of the virtual characters to the participant, the greater the level of physiological arousal. Physiological arousal was measured by the number of skin conductance responses within a short time period after the approach, and the maximum change in skin conductance level 5 s after the approach. The virtual characters were each either female or a cylinder of human size, and one or four characters approached each subject a total of 12 times. Twelve male subjects were recruited for the experiment. The results suggest that the number of skin conductance responses after the approach and the change in skin conductance level increased the closer the virtual characters approached toward the participants. Moreover, these response variables were inversely correlated with the number of visits, showing a typical adaptation effect. There was some evidence to suggest that the number of characters who simultaneously approached (one or four) was positively associated with the responses. Surprisingly there was no evidence of a difference in response between the humanoid characters and cylinders on the basis of this physiological data. It is suggested that the similarity in this quantitative arousal response to virtual characters and virtual objects might mask a profound difference in qualitative response, an interpretation supported by questionnaire and interview results. Overall the experiment supported the premise that people exhibit heightened physiological arousal the closer they are approached by virtual characters.

Proxemics with multiple dynamic characters in an immersive virtual environment

An experiment was carried out to examine the impact on electrodermal activity of people when approached by groups of one or four virtual characters at varying distances. It was premised on the basis of proxemics theory that the closer the approach of the virtual characters to the participant, the greater the level of physiological arousal. Physiological arousal was measured by the number of skin conductance responses within a short time period after the approach, and the maximum change in skin conductance level 5 s after the approach. The virtual characters were each either female or a cylinder of human size, and one or four characters approached each subject a total of 12 times. Twelve male subjects were recruited for the experiment. The results suggest that the number of skin conductance responses after the approach and the change in skin conductance level increased the closer the virtual characters approached toward the participants. Moreover, these response variables were inversely correlated with the number of visits, showing a typical adaptation effect. There was some evidence to suggest that the number of characters who simultaneously approached (one or four) was positively associated with the responses. Surprisingly there was no evidence of a difference in response between the humanoid characters and cylinders on the basis of this physiological data. It is suggested that the similarity in this quantitative arousal response to virtual characters and virtual objects might mask a profound difference in qualitative response, an interpretation supported by questionnaire and interview results. Overall the experiment supported the premise that people exhibit heightened physiological arousal the closer they are approached by virtual characters.

Evolving techniques to evaluate ejaculatory function.

PURPOSE OF REVIEW: Recent findings in the physiology and neurobiology of ejaculation have expanded our understanding of male sexual function and have allowed the development of new instruments to investigate ejaculatory and orgasmic disorders. RECENT FINDINGS: The evidence-based definition of lifelong premature ejaculation has set a model in the evaluation and treatment outcome of sexual dysfunction. New instruments to objectively assess arousal, orgasm and the expulsion phase of ejaculation such as functional MRI, dynamic pelvic ultrasound, PET scans and validated questionnaires have lead to a better understanding of sexual dysfunction in men. Animal models, developments in neurobiology and clinical experience have transformed a purely psychoanalytical approach to ejaculatory and orgasmic function into a novel multidisciplinary, scientifically sound and evidence-based discipline of medicine. SUMMARY: Ejaculation is an integral part of normal sexual function. Ejaculatory dysfunction is common and may cause substantial disruption to the quality of a patient's life. A better understanding of the epidemiology, pathophysiology, neuroscience and genetics of ejaculatory and orgasmic function will eventually lead to the development of new, effective methods of treatment of disorders of ejaculation and orgasm in men.

Efecto placebo en el tratamiento conductual del insomnio : un enfoque desde las diferencias individuales

En el trabajo que se presenta se revisan varias investigaciones sobre el tratamiento conductual del insomnio de conciliación en los que se utilizan procedimientos de control placebo. Se encuentra que los procedimientos diseñados como control placebo causan diferentes efectos sobre la disminución de la latencia inicial de sueño, por lo que se infiere que por su naturaleza los distintos procedimientos diseñados inciden inespecíficamente en los sujetos insomnes.Se intenta buscar analogías hipotéticas sobre las diferencias individuales desde la perspectiva de la teoría de la Atribución (Storms & Nisbett, 1970; Brockner & Swap, 1983) y la hipótesis Extraversión-Arousal (Eysenck, 1967). Se sugiere que se incluyan las diferencias individuales como variables independientes en los futuros diseños en los que se utilicen procedimientos de atención placebo.

An Analysis of Eye Scanpath Entropy in a Progressively Forming Virtual Environment

A sign of presence in virtual environments is that people respond to situations and events as if they were real, where response may be considered at many different levels, ranging from unconscious physiological responses through to overt behavior,emotions, and thoughts. In this paper we consider two responses that gave different indications of the onset of presence in a gradually forming environment. Two aspects of the response of people to an immersive virtual environment were recorded: their eye scanpath, and their skin conductance response (SCR). The scenario was formed over a period of 2 min, by introducing an increasing number of its polygons in random order in a head-tracked head-mounted display. For one group of experimental participants (n 8) the environment formed into one in which they found themselves standing on top of a 3 m high column. For a second group of participants (n 6) the environment was otherwise the same except that the column was only 1 cm high, so that they would be standing at normal ground level. For a third group of participants (n 14) the polygons never formed into a meaningful environment. The participants who stood on top of the tall column exhibited a significant decrease in entropy of the eye scanpath and an increase in the number of SCR by 99 s into the scenario, at a time when only 65% of the polygons had been displayed. The ground level participants exhibited a similar decrease in scanpath entropy, but not the increase in SCR. The random scenario grouping did not exhibit this decrease in eye scanpath entropy. A drop in scanpath entropy indicates that the environment had cohered into a meaningful perception. An increase in the rate of SCR indicates the perception of an aversive stimulus. These results suggest that on these two dimensions (scanpath entropy and rate of SCR) participants were responding realistically to the scenario shown in the virtual environment. In addition, the response occurred well before the entire scenario had been displayed, suggesting that once a set of minimal cues exists within a scenario,it is enough to form a meaningful perception. Moreover, at the level of the sympathetic nervous system, the participants who were standing on top of the column exhibited arousal as if their experience might be real. This is an important practical aspect of the concept of presence.

Using music as a signal for biofeedback

Studies on the potential benefits of conveying biofeedback stimulus using a musical signal have appeared in recent years with the intent of harnessing the strong effects that music listening may have on subjects. While results are encouraging, the fundamental question has yet to be addressed, of how combined music and biofeedback compares to the already established use of either of these elements separately. This experiment, involving young adults (N = 24), compared the effectiveness at modulating participants' states of physiological arousal of each of the following conditions: A) listening to pre-recorded music, B) sonification biofeedback of the heart rate, and C) an algorithmically modulated musical feedback signal conveying the subject's heart rate. Our hypothesis was that each of the conditions (A), (B) and (C) would differ from the other two in the extent to which it enables participants to increase and decrease their state of physiological arousal, with (C) being more effective than (B), and both more than (A). Several physiological measures and qualitative responses were recorded and analyzed. Results show that using musical biofeedback allowed participants to modulate their state of physiological arousal at least equally well as sonification biofeedback, and much better than just listening to music, as reflected in their heart rate measurements, controlling for respiration-rate. Our findings indicate that the known effects of music in modulating arousal can therefore be beneficially harnessed when designing a biofeedback protocol.

The down-regulation of disgust by implementation intentions: experiential and physiological concomitants

Emotion regulation plays a key role in mental health and psychopathology. Therefore, it seems important to develop effective forms of emotion regulation. Implementation intentions are if-then plans that help people attain their self-regulatory goals. Perspective-taking and response-focused implementation intentions have been shown to reduce feelings of unpleasantness and arousal, respectively, in response to briefly presented disgusting pictures. The present study addressed the open research questions whether forming these types of implementation intentions is effective in regulating affect during prolonged presentation of disgusting pictures, and whether it is associated with changes in physiological arousal. Eighty-one participants viewed disgusting, neutral, and pleasant pictures of 6 s duration under four instructions: the goal intention to not get disgusted, this goal intention furnished with a perspective-taking or a response-focused implementation intention, and no emotion regulation instructions. The dependent variables were ratings of disgust, valence, arousal, and electrodermal activity. Only perspective-taking implementation intention participants significantly reduced their disgust and unpleasantness as compared to goal-intention and control participants. Arousal and skin conductance did not significantly differ between conditions. The effectiveness of response-focused but not perspective-taking implementation intentions seems to be substantially reduced during sustained exposure duration.

The central histaminergic neurons in vitro, and their neuroprotective role in excitotoxic cell death in the postnatal rat hippocampus.

Histamine acts as a neurotransmitter in the central nervous system. Brain histamine in synthesized in neurons located to the posterior hypothalamus, from where these neurons send their projections to different parts of the brain. Released histamine participates in the regulation of several physiological functions such as arousal, attention and body homeostasis. Disturbances in the histaminergic system have been detected in diseases such as epilepsy, sleep disorders, anxiety, depression, Alzheimer’s disease, and schizophrenia. The purpose of this thesis was to develop optimal culture conditions for the histaminergic neurons, to study their detailed morphology, and to find out their significance in the kainic acid (KA)-induced neuronal death in the immature rat hippocampus. The morphology of the histaminergic neurons in vitro was comparable with the earlier findings. Histamine-containing vesicles were found in the axon but also in the cell body and dendrites suggesting a possibility for the somatodendritic release. Moreover, histamine was shown to be colocalized with the vesicular monoamine transporter 2 (VMAT2) suggesting that VMAT2 transports histamine to the subcellular storage vesicles. Furthermore, histamine was localized with γ-aminobutyric acid (GABA) in distinct storage vesicles and with neuropeptide galanin partly in the same storage vesicles suggesting different corelease mechanisms for GABA and galanin with histamine. In the organotypic hippocampal slice cultures, KA-induced neuronal death was first detected 12 h after the treatment being restricted mainly to the CA3 subregion. Moreover, cell death was irreversible, since the 48 h recovery period did not save the cells, but instead increased the damage. Finally, neuronal death was suggested to be necrotic, since intracellular apoptotic pathways were not activated, and the morphological changes detected with the electron microscopy were characteristic for necrosis. In the coculture system of the hippocampal and posterior hypothalamic slices, histaminergic neurons significantly decreased epileptiform burst activity and neuronal death in the hippocampal slices, this effect being mediated by histamine 1 (H1) and 3 (H3) receptors. In conclusion, the histaminergic neurons were maintained succesfully in the in vitro conditions exhibiting comparable morphological characteristics as detected earlier in vivo. Moreover, they developed functional innervations within the hippocampal slices in the coculture system. Finally, the KA-induced regionspecific, irreversible and necrotic hippocampal pyramidal cell damage was significantly decreased by the histaminergic neurons through H1 and H3 receptors.

Scoring criteria for portable monitor recordings: a comparison of four hypopnoea definitions in a population-based cohort.

RATIONALE: Limited-channel portable monitors (PMs) are increasingly used as an alternative to polysomnography (PSG) for the diagnosis of obstructive sleep apnoea (OSA). However, recommendations for the scoring of PM recordings are still lacking. Pulse-wave amplitude (PWA) drops, considered as surrogates for EEG arousals, may increase the detection sensitivity for respiratory events in PM recordings. OBJECTIVES: To investigate the performance of four different hypopnoea scoring criteria, using 3% or 4% oxygen desaturation levels, including or not PWA drops as surrogates for EEG arousals, and to determine the impact of measured versus reported sleep time on OSA diagnosis. METHODS: Subjects drawn from a population-based cohort underwent a complete home PSG. The PSG recordings were scored using the 2012 American Academy of Sleep Medicine criteria to determine the apnoea-hypopnoea index (AHI). Recordings were then rescored using only parameters available on type 3 PM devices according to different hypopnoea criteria and patients-reported sleep duration to determine the 'portable monitor AHIs' (PM-AHIs). MAIN RESULTS: 312 subjects were included. Overall, PM-AHIs showed a good concordance with the PSG-based AHI although it tended to slightly underestimate it. The PM-AHI using 3% desaturation without PWA drops showed the best diagnostic accuracy for AHI thresholds of ≥5/h and ≥15/h (correctly classifying 94.55% and 93.27% of subjects, respectively, vs 80.13% and 87.50% with PWA drops). There was a significant but modest correlation between PWA drops and EEG arousals (r=0.20, p=0.0004). CONCLUSION: Interpretation of PM recordings using hypopnoea criteria which include 3% desaturation without PWA drops as EEG arousal surrogate showed the best diagnosis accuracy compared with full PSG.

Personality effects and sex differences on the international affective picture system (IAPS) : a Spanish and Swiss study

The present study analyses the relationship between Anxiety and Impulsivity personality factors and emotions, by controlling for country and sex effects in a sample of Spanish and Swiss university students. Emotions were assessed through the International Affective Picture System (IAPS) of pictures (valence/arousal) using the Self-Assessment Manikin (SAM) procedure. The mixed valence/arousal groups' pictures were formed according to Tok, Koyuncu, Dural and Catikkas procedure (2010). Results showed that females scored significantly higher in Anxiety factor and men in Impulsivity factor in both countries. The effect of sex was highly significant for Anxiety (ŋ2: 0.12), but there was no significant effect of the country. Also, females obtained higher scores in the four valence/arousal pictures groups. The sex effect was particularly robust for negative valence-high arousal (ŋ2: 0.13). Impulsivity correlated with high ratings of positive valence-high arousal while Anxiety correlated with high ratings of negative valence-high arousal and with high ratings of negative valence-low arousal in both sexes, although scores were higher for females. Structural Equation Modelling confirmed these relationships. Nevertheless, Anxiety and Impulsivity explained only a small amount of the accounted variance of the self-reported valence and arousal of the pictures.