The periodic repolarization dynamics index identifies changes in ventricular repolarization oscillations associated with music-induced emotions

The effect of music on cardiovascular dynamics may be useful in a variety of clinical settings. The aim of this study was to assess whether listening to music characterized by different emotional valence affected ventricular periodic repolarization dynamics (PRD), a recently-proposed non-invasive index of sympathetic ventricular modulation. The 12 lead ECG was recorded in 71 healthy volunteers exposed to six 90 s excerpts of pleasant music and unpleasant acoustic stimuli as well as six 90 s intervals of silence. A 20 s interval was allowed between excerpts during which the participants were asked to evaluate the previous excerpt. A simulation study was carried out to assess the capability of the algorithm of tracking fast small changes in PRD. The simulation study shows that the algorithm implemented in this study has a time-frequency resolution sufficient to capture the fast dynamics observed in this study. PRD were higher during listening to both pleasant and unpleasant music than during silence. There was a (weak) trend for the PRD to be higher during listening to pleasant than unpleasant music that may indicate the existence of a (weak) interaction between the valence of music-induced emotions and sympathetic ventricular response. The PRD significantly increased during the 20 s interval in between conditions, possibly reflecting a sympathetic response to the evaluation task and/or to the expectation of the following excerpt

The Effect of Emotional Valence on Ventricular Repolarization Dynamics Is Mediated by Heart Rate Variability: A Study of QT Variability and Music-Induced Emotions

Background: Emotions can affect cardiac activity, but their impact on ventricular repolarization variability, an important parameter providing information about cardiac risk and autonomic nervous system activity, is unknown. The beat-to-beat variability of the QT interval (QTV) from the body surface ECG is a non-invasive marker of repolarization variability, which can be decomposed into QTV related to RR variability (QTVrRRV) and QTV unrelated to RRV (QTVuRRV), with the latter thought to be a marker of intrinsic repolarization variability. Aim: To determine the effect of emotional valence (pleasant and unpleasant) on repolarization variability in healthy volunteers by means of QTV analysis. Methods: 75 individuals (24.5 ± 3.2 years, 36 females) without a history of cardiovascular disease listened to music-excerpts that were either felt as pleasant (n = 6) or unpleasant (n = 6). Excerpts lasted about 90 s and were presented in a random order along with silent intervals (n = 6). QTV and RRV were derived from the ECG and the time-frequency spectrum of RRV, QTV, QTVuRRV and QTVrRRV as well as time-frequency coherence between QTV and RRV were estimated. Analysis was performed in low-frequency (LF), high frequency (HF) and total spectral bands. Results: The heart rate-corrected QTV showed a small but significant increase from silence (median 347/interquartile range 31 ms) to listening to music felt as unpleasant (351/30 ms) and pleasant (355/32 ms). The dynamic response of QTV to emotional valence showed a transient phase lasting about 20 s after the onset of each musical excerpt. QTV and RRV were highly correlated in both HF and LF (mean coherence ranging 0.76–0.85). QTV and QTVrRRV decreased during listening to music felt as pleasant and unpleasant with respect to silence and further decreased during listening to music felt as pleasant. QTVuRRV was small and not affected by emotional valence. Conclusion: Emotional valence, as evoked by music, has a small but significant effect on QTV and QTVrRRV, but not on QTVuRRV. This suggests that the interaction between emotional valence and ventricular repolarization variability is mediated by cycle length dynamics and not due to intrinsic repolarization variability

Bioelectric Signal Analysis to Expose Nervous Control of the Human Heart

This thesis describes the development of new methods to infer the nature of nervous control of the human heart using recordings of its electrical behaviour. Malfunctions of this control system are a leading cause of death, and can be triggered by a diverse range of influences including basic physiological factors and one’s emotional state. However, the mechanisms of failure remain poorly understood, partly due to a lack of relevant human data. The principal purpose of the work described in this thesis is to improve the availability of such data. A literature review was conducted, covering the current understanding of electrical activity in the heart and its control by the nervous system, as well as the techniques available to observe that behaviour. A variety of novel techniques were developed and implemented experimentally to demonstrate their utility. Specialised methods for the filtering and subsequent spectral analysis of electrocardiograph (ECG) signals were used to expose differences between psychologically distinct groups in terms of their response to emotional stimuli. Algorithms were developed to automatically process unipolar electrogram recordings with minimal human intervention, enabling the analysis of heterogeneous electrophysiological dynamics, which requires datasets of a size that would otherwise make in-depth analyses intractable. New indices were developed for measuring the timing of localised electrical activation and recovery from unipolar electrograms, in order to overcome the fact that conventional indices are not well suited to dynamic analyses. Experiments using these tools demonstrated that respiration induces heart-rate independent modulation of the ventricles’ electrophysiological behaviour via the autonomic nervous system. By improving the accessibility of human in situ data, the developed tools enable new research methodologies to study interactions between the heart and the nervous system, which may ultimately contribute to the development of new treatments to prevent thousands of deaths in the UK alone each year

Serotonergic modulation of the ventral pallidum by 5HT1A, 5HT5A, 5HT7 AND 5HT2C receptors

Introduction: Serotonin's involvement in reward processing is controversial. The large number of serotonin receptor sub-types and their individual and unique contributions have been difficult to dissect out, yet understanding how specific serotonin receptor sub-types contribute to its effects on areas associated with reward processing is an essential step. Methods: The current study used multi-electrode arrays and acute slice preparations to examine the effects of serotonin on ventral pallidum (VP) neurons. Approach for statistical analysis: extracellular recordings were spike sorted using template matching and principal components analysis, Consecutive inter-spike intervals were then compared over periods of 1200 seconds for each treatment condition using a student’s t test. Results and conclusions: Our data suggests that excitatory responses to serotonin application are pre-synaptic in origin as blocking synaptic transmission with low-calcium aCSF abolished these responses. Our data also suggests that 5HT1a, 5HT5a and 5HT7 receptors contribute to this effect, potentially forming an oligomeric complex, as 5HT1a antagonists completely abolished excitatory responses to serotonin application, while 5HT5a and 5HT7 only reduced the magnitude of excitatory responses to serotonin. 5HT2c receptors were the only serotonin receptor sub-type tested that elicited inhibitory responses to serotonin application in the VP. These findings, combined with our previous data outlining the mechanisms underpinning dopamine's effects in the VP, provide key information, which will allow future research to fully examine the interplay between serotonin and dopamine in the VP. Investigation of dopamine and serotonins interaction may provide vital insights into our understanding of the VP's involvement in reward processing. It may also contribute to our understanding of how drugs of abuse, such as cocaine, may hijack these mechanisms in the VP resulting in sensitization to drugs of abuse

Functional and neural mechanisms of human fear conditioning: studies in healthy and brain-damaged individuals

Fear conditioning represents the learning process by which a stimulus, after repeated pairing with an aversive event, comes to evoke fear and becomes intrinsically aversive. This learning is essential to organisms throughout the animal kingdom and represents one the most successful laboratory paradigm to reveal the psychological processes that govern the expression of emotional memory and explore its neurobiological underpinnings. Although a large amount of research has been conducted on the behavioural or neural correlates of fear conditioning, some key questions remain unanswered. Accordingly, this thesis aims to respond to some unsolved theoretic and methodological issues, thus furthering our understanding of the neurofunctional basis of human fear conditioning both in healthy and brain-damaged individuals. Specifically, in this thesis, behavioural, psychophysiological, lesion and non-invasive brain stimulation studies were reported. Study 1 examined the influence of normal aging on context-dependent recall of extinction of fear conditioned stimulus. Study 2 aimed to determine the causal role of the ventromedial PFC (vmPFC) in the acquisition of fear conditioning by systematically test the effect of bilateral vmPFC brain-lesion. Study 3 aimed to interfere with the reconsolidation process of fear memory by the means of non-invasive brain stimulation (i.e. TMS) disrupting PFC neural activity. Finally, Study 4 aimed to investigate whether the parasympathetic – vagal – modulation of heart rate might reflect the anticipation of fearful, as compared to neutral, events during classical fear conditioning paradigm. Evidence reported in this PhD thesis might therefore provide key insights and deeper understanding of critical issues concerning the neurofunctional mechanisms underlying the acquisition, the extinction and the reconsolidation of fear memories in humans

Investigating Cerebellar Mechanisms of Schizophrenia by Using a Pharmacological Mouse Model: Regulation of Voltage-Gated Potassium Channels

Schizophrenia is a heterogeneous psychiatric disorder which affects at least 1% of the global population. Its complex pathology involves impaired neuronal communication that leads to the onset of debilitating symptoms affecting behaviour and cognition. Voltage-gated potassium (Kv) channels are fundamental to neuronal communication because of their intricate roles in regulating neuronal excitability, thereby governing information processing in the brain. The cerebellum has a significant influence over how this information is communicated across the brain because of its interconnectivity with virtually all brain regions. To expand our understanding of Kv channels, this thesis investigates the regulation of three alpha subunits of voltage-gated potassium channels Kv2.1, Kv6.4, and Kv3.1b in the cerebellar cortex of a phencyclidine-induced mouse model of schizophrenia and explores their potential role in schizophrenia symptoms. In Chapter 3 we show using immunohistochemistry that Kv2.1 is expressed in the Purkinje cells and granule cells as membrane-bound clusters in the soma and proximal dendrites, whereas the Kv6.4 are mainly present in the cytosol. Additionally, using proximity ligation we demonstrated for the first time that Kv6.4 arrange with Kv2.1 to form heteromeric channels on the perisomatic membrane of Purkinje cells. These findings suggest that Kv2.1 and Kv6.4 may act as neuronal ‘transistors’ thereby controlling the frequency of neuronal firing in these cell populations. In Chapter 4 we describe the behavioural phenotype of our CBA/CA phencyclidine model to include altered exploratory patterns, changes in locomotor activity, and changes in rearing and grooming behaviours. We also observed dysregulation of NMDA-receptor genes in frontal cortex and the cerebellum, and abnormalities in several features of the cerebellum of the model mice. Additionally, we describe the effectiveness of concomitant antipsychotic agents haloperidol and clozapine in attenuating the acute changes in behaviour induced by phencyclidine, and we introduce specific motor function tests to assess cerebellar involvement in the model. Together, these findings support several aspects of face, construct, and predictive validity expected of a schizophrenia model. Finally in Chapter 5 we investigate the cerebellar regulation of the three Kv subunits in our animal model, where we found Kv2.1 downregulation in the cerebellar cortex which is consistent with findings from human schizophrenia subjects and from animal studies. Strikingly, we found that the Kv6.4 is upregulated in several regions of the cerebellum that was supported by upregulated Kcng4 gene, which may indicate a compensatory mechanism for Kv2.1 loss. Additionally, we observed downregulation of the Kv3.1b in the granule cell layer of the right cerebellar lateral hemisphere, which may indicate a local functional demand. In conclusion, this thesis demonstrates, by using a range of behavioural, histological, and biomolecular investigations, the cerebellar pathology resulting from subchronic phencyclidine treatment, and also elucidates the functional role of Kv channels in a schizophrenia-like pathological state

Aerospace medicine and biology, an annotated bibliography. volume xi- 1962-1963 literature

Aerospace medicine and biology - annotated bibliography for 1962 and 196