Armand Mensen

Humor as a Reward Mechanism: Event-Related Potentials in the Healthy and Diseased Brain

Humor processing involves distinct processing stages including incongruity detection, emotional response, and engagement of mesolimbic reward regions. Dysfunctional reward processing and clinical symptoms in response to humor have been previously described in both hypocretin deficient narcolepsy-cataplexy (NC) and in idiopathic Parkinson disease (PD). For NC patients, humor is the strongest trigger for cataplexy, a transient loss of muscle tone, whereas dopamine-deficient PD-patients show blunted emotional responses to humor. To better understand the role of reward system and the various contributions of hypocretinergic and dopaminergic mechanisms to different stages of humor processing we examined the electrophysiological response to humorous and neutral pictures when given as reward feedback in PD, NC and healthy controls. Humor compared to neutral feedback demonstrated modulation of early ERP amplitudes likely corresponding to visual processing stages, with no group differences. At 270 ms post-feedback, conditions showed topographical and amplitudinal differences for frontal and left posterior electrodes, in that humor feedback was absent in PD patients but increased in NC patients. We suggest that this effect relates to a relatively early affective response, reminiscent of increased amygdala response reported in NC patients. Later ERP differences, corresponding to the late positive potential, revealed a lack of sustained activation in PD, likely due to altered dopamine regulation in reward structures in these patients. This research provides new insights into the temporal dynamics and underlying mechanisms of humor detection and appreciation in health and disease.

The effects of theta-burst stimulation on sleep and vigilance in humans

Repetitive transcranial magnetic stimulation (TMS) has become a popular tool to modulate neuronal networks and associated brain functions in both clinical and basic research. Yet few studies have examined the potential effects of cortical stimulation on general levels of vigilance. In this exploratory study, we used theta-burst protocols, both continuous (cTBS) and intermittent (iTBS) patterns, to examine whether inhibition or excitation of the left dorso-lateral prefrontal cortex (dlPFC) was able to induce reliable and acute changes to vigilance measures, compared to the left dorso-lateral associative visual cortex (dlAVC) as a control site in line with previous work. Partially sleep restricted participants underwent four separate sessions in a single day, in a between subjects design for TBS stimulation type and within subjects for locaton, each consisting of maintenance of wakefulness test (MWT), a sleep latency test, and a psychomotor vigilance task (PVT). TBS significantly affected measures of sleep consolidation, namely latency to sleep stage 2 and sleep efficiency, but had no effects on sleep drive or psychomotor vigilance levels for either TBS type or location. Contrary to our initial hypothesis of the dlAVC as a control site, stimulation to this region resulted in the largest differential effects between stimulation types. Moreover, the effect of TBS was found to be consistent throughout the day. These data may provide the basis for further investigation into therapeutic applications of TBS in sleep disorders.

Time perception in narcolepsy in comparison to patients with Parkinson's disease and healthy controls—an exploratory study

The striatum and the prefrontal cortex play an important role in cognitive time processing, and time perception depends on sustained attention. Narcolepsy patients are unable to maintain sustained attention, due probably to deficient hypocretin signalling. Impaired time perception has been found in Parkinsons disease (PD) and attributed to a dysfunctional dopaminergic striatal pacemaker. We aimed to assess time perception in patients with narcolepsy and PD and to compare the outcome to healthy control participants. Seventeen narcolepsy patients, 12 PD patients and 15 healthy controls performed a short time production task, where they had to produce an interval of 1, 2 or 5 s. The accuracy of time production differed significantly according to task target duration, and there was a trend towards a group difference with narcolepsy patients tending to overproduce all target durations. Absolute variability was significantly different between groups, with narcolepsy patients showing higher absolute variability in comparison to controls and PD patients. The analysis of the temporal course of time estimation showed more pronounced overproduction of each target duration at the end of each trial in narcolepsy patients, whereas performance was more or less stable in controls and PD patients. Overproduction and higher variability of all time durations in narcolepsy indicate impaired short interval timing in the seconds range, while the scalar property of timing was preserved. The time–course of accuracy and variability of time production within sessions indicate an attention‐related mechanism of impaired interval timing.

The Roles of Dopamine and Hypocretin in Reward: A Electroencephalographic Study.

The proper functioning of the mesolimbic reward system is largely dependent on the neurotransmitter dopamine. Recent evidence suggests that the hypocretin system has significant projections to this reward system. We examined the distinct effects of reduced dopamine or reduced hypocretin levels on reward activity in patients with Parkinson’s disease, dopamine deficient, as well as patients with narcolepsy-cataplexy, hypocretin depleted, and healthy controls. Participants performed a simple game-like task while high-density electroencephalography was recorded. Topography and timing of event-related potentials for both reward cue, and reward feedback was examined across the entire dataset. While response to reward cue was similar in all groups, two distinct time points were found to distinguish patients and controls for reward feedback. Around 160ms both patient groups had reduced ERP amplitude compared to controls. Later at 250ms, both patient groups also showed a clear event-related potential (ERP), which was absent in controls. The initial differences show that both patient groups show a similar, blunted response to reward delivery. The second potential corresponds to the classic feedback-related negativity (FRN) potential which relies on dopamine activity and reflects reward prediction-error signaling. In particular the mismatch between predicted reward and reward subsequently received was significantly higher in PD compared to NC, independent of reward magnitude and valence. The intermediate FRN response in NC highlights the contribution of hypocretin in reward processing, yet also shows that this is not as detrimental to the reward system as in Parkinson’s. Furthermore, the inability to generate accurate predictions in NC may explain why hypocretin deficiency mediates cataplexy triggered by both positive and negative emotions.

The occurrence of individual slow waves in sleep is predicted by heart rate

The integration of near-infrared spectroscopy and electroencephalography measures presents an ideal method to study the haemodynamics of sleep. While the cortical dynamics and neuro-modulating influences affecting the transition from wakefulness to sleep is well researched, the assumption has been that individual slow waves, the hallmark of deep sleep, are spontaneously occurring cortical events. By creating event-related potentials from the NIRS recording, time-locked to the onset of thousands of individual slow waves, we show the onset of slow waves is phase-locked to an ongoing oscillation in the NIRS recording. This oscillation stems from the moment to moment fluctuations of light absorption caused by arterial pulsations driven by the heart beat. The same oscillating signal can be detected if the electrocardiogram is time-locked to the onset of the slow wave. The ongoing NIRS oscillation suggests that individual slow wave initiation is dependent on that signal, and not the other way round. However, the precise causal links remain speculative. We propose several potential mechanisms: that the heart-beat or arterial pulsation acts as a stimulus which evokes a down-state; local fluctuations in energy supply may lead to a network effect of hyperpolarization; that the arterial pulsations lead to corresponding changes in the cerebral-spinal-fluid which evokes the slow wave; or that a third neural generator, regulating heart rate and slow waves may be involved.

M-N-125 REACTION TIME IN A MONETARY INCENTIVE TASK DOES NOT DIFFER BETWEEN NARCOLEPSY PATIENTS AND HEALTHY CONTROLS

of the drugs used for treatment. The Minnesota Multiphasic Personality Inventory (MMPI) is the clinical test used most frequently to identify personality profiles and for diagnosing different psychopathologies. It is composed of multiple scales, including six critical variables with a greater influence in the treatment decision. Materials and Methods: We have performed a comparative and observational study using the latest version of the MMPI-2RF in 10 patients in our sleep laboratory diagnosed with Primary Hypersomnia. The range of age was 18 to 40 years. 7 of them had Narcolepsy, 3 of them with Cataplexy, and 3 had Idiophatic Hypersomnia. None of them had a history of psychiatric or somatic problems. The education level of the patients was at least the high school level. We compared the results with 10 healthy controls with similar demographic characteristics but without sleep disorder. Previous informed consent was obtained from all patients. Results: Preliminary results showed in patients a high level of demoralization, somatization, absence of positive emotions, hopelessness and no motivation for change. Many patients showed a propensity for violence, familial conflicts and impulsivity. None of these characteristics were identified in the control group. We performed a statistical analysis with the data. In a discriminant analysis between the critical variables, we found that a combination of two factors, specifically anxiety (AXY) and defenselessness (HLP), were capable of separating patients from the control subjects. Conclusion: Based on preliminary data we have found a specific psychopathological profile in patients with Primary Hypersomnia but a more detailed and extensive study is needed to provide consistent data. In our experience, we suggest that these patients need specific psychological support.