P105 Endocrine, autonomic and vascular function in children with Sleep Disordered Breathing

SDB is a risk factor for cardiovascular disease and co-exists with chronic endocrine disorders such as type II diabetes and metabolic syndrome. Children with SDB have increased blood flow velocity, an indicator of reduced vascular compliance and early vascular aging. Increased blood flow velocity is positively associated with sympathetic activity, increased arterial sympathetic nerve fibre density and endothelial damage. Whether changes in endocrine function occur concomitantly with altered autonomic and vascular function in children with SDB was assessed. Thirty six children scheduled for tonsillectomy underwent overnight polysomnography (SDB severity), pupil light reflex (autonomic function), fasting brachial artery blood flow assessment (vascular function - Doppler Ultrasound). Leptin and Ghrelin - both hormonal markers associated with sympathetic activity were measured in urine using ELISA and serum using MagPlex. The following dimensions of the dorsal lingual artery (tonsil) were measured – medial thickness, medial area, smooth muscle cell number/layers. We observed a positive correlation between serum and urine leptin and ghrelin concentrations. Increased blood flow velocity and arterial medial thickness were both associated with increased serum and urine leptin and ghrelin concentrations. Pupil light reflex was negatively associated with serum leptin and ghrelin levels. OAHI was positively correlated with leptin and ghrelin concentration (urine and serum) but not blood flow velocity. Blood flow velocity was inversely correlated with SpO2 nadir (REM). Our findings suggest that SDB has a global effect on the autonomic, vascular and endocrine systems.The impact of untreated paediatric SDB on the development of comorbidities in later life needs urgent attention.

Analysis of pupillometer results according to disease stage in patients with Parkinson’s disease

We performed pupillometer testing on 132 patients with Parkinson’s disease, stratified into two groups according to the disease stage. Neurological examinations and pupillometry were performed in the ON state. Patients in the Hoehn and Yahr stages 1 and 2 comprised the early group, and patients in stages 3–5 formed the late group. We performed age- and sex-matched (2:1) propensity score matching to compensate for the effect of age on pupil light reflex. Eight pupillometer parameters were measured and compared between the two groups. After the propensity score matching, the early group had 64 patients and the late group had 32 patients. The late group had a longer disease duration and took a higher levodopa equivalent dose than the early group. The constriction velocity (P = 0.006) and maximum constriction velocity (P = 0.005) were significantly faster in the early group than in the late group. Pupil size, minimum diameter, and dilation velocity were similar in both groups. The pupillary contraction velocity decreased with the disease progression, suggesting that the progression of Parkinson’s disease could be identified by the pupil constriction velocity.

Analysis of pupillometer results according to motor symptom severity in patients with Parkinson’s disease

We performed pupillometer testing on 132 patients with Parkinson’s disease, stratified into two groups according to the disease severity. Neurological examinations and pupillometry were performed in the ON state. Patients in the Hoehn and Yahr stages 1 and 2 comprised the early group, and patients in stages 3-5 formed the late group. We performed age- and sex-matched (2:1) propensity score matching to compensate for the effect of age on pupil light reflex. Eight pupillometer parameters were measured and compared between the two groups. After the propensity score matching, the early group had 64 patients and the late group had 32 patients. The late group had a longer disease duration and took a higher levodopa equivalent dose than the early group. The constriction velocity (P=0.006) and maximum constriction velocity (P=0.005) were significantly faster in the early group than in the late group. Pupil size, minimum diameter, and dilation velocity were similar in both groups. The pupillary contraction velocity decreased with the disease progression, suggesting that the progression of Parkinson’s disease could be identified by the pupil constriction velocity.

Melanopsin Cell Dysfunction is Involved in Sleep Disruption in Parkinson’s Disease

Background: Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) signal the environmental light to mediate circadian photoentrainment and sleep-wake cycles. There is high prevalence of circadian and sleep disruption in people with Parkinson’s disease, however the underlying mechanisms of these symptoms are not clear. Objective: Based on recent evidence of anatomical and functional loss of melanopsin ganglion cells in Parkinson’s disease, we evaluate the link between melanopsin function, circadian, and sleep behavior. Methods: The pupil light reflex and melanopsin-mediated post-illumination pupil response were measured using chromatic pupillometry in 30 optimally medicated people with Parkinson’s disease and 29 age-matched healthy controls. Circadian health was determined using dim light melatonin onset, sleep questionnaires, and actigraphy. Ophthalmic examination quantified eye health and optical coherence tomography measured retinal thickness. Results: The melanopsin-mediated post-illumination pupil response amplitudes were significantly reduced in Parkinson’s disease (p < 0.0001) and correlated with poor sleep quality (r2 = 33; p < 0.001) and nerve fiber layer thinning (r2 = 0.40; p < 0.001). People with Parkinson’s disease had significantly poorer sleep quality with higher subjective sleep scores (p < 0.05) and earlier melatonin onset (p = 0.01). Pupil light (outer retinal) response metrics, daily light exposure and outer retinal thickness were similar between the groups (p > 0.05). Conclusion: Our evidence-based data identify a mechanism through which inner retinal ipRGC dysfunction contributes to sleep disruption in Parkinson’s disease in the presence of normal outer retinal (rod-cone photoreceptor) function. Our findings provide a rationale for designing new treatment approaches in Parkinson’s disease through melanopsin photoreceptor-targeted light therapies for improving sleep-wake cycles.

Dopamine influences attentional rate modulation in Macaque posterior parietal cortex

Selective attention facilitates the prioritization of task-relevant sensory inputs over those which are irrelevant. Although cognitive neuroscience has made great strides in understanding the neural substrates of attention, our understanding of its neuropharmacology is incomplete. Cholinergic and glutamatergic contributions have been demonstrated, but emerging evidence also suggests an important influence of dopamine (DA). DA has historically been investigated in the context of frontal/prefrontal function arguing that dopaminergic receptor density in the posterior/parietal cortex is sparse. However, this notion was derived from rodent data, whereas in primates DA innervation in parietal cortex matches that of many prefrontal areas. We recorded single- and multi-unit activity whilst iontophoretically administering dopaminergic agonists and antagonists to posterior parietal cortex of rhesus macaques engaged in a spatial attention task. Out of 88 neurons, 50 showed modulation of activity induced by drug administration. Dopamine inhibited firing rates across the population according to an inverted-U shaped dose-response curve. D1 receptor antagonists diminished firing rates in broad-spiking units according to a monotonically increasing function. Additionally, dopamine modulated attentional signals in broad, but not narrow-spiking cells. Finally, both drugs modulated the pupil light reflex. These data show that dopamine plays an important role in shaping neuronal responses and modulates attentional processing in macaque parietal cortex.Significance statementDopamine is critically involved in high-level cognitive functions, and dopaminergic dysfunctions pertain to ageing and neurological and psychiatric disorders. Most previous studies focused on dopaminergic effects on prefrontal activity or its role in basal ganglia circuitry. The effects of dopamine in other brain areas such as parietal cortex, despite its well-established role in cognition and cognitive dysfunction, have largely been overlooked. This study is the first to show dopaminergic modulation of parietal activity in general, and specific to spatial attention in the non-human primate, revealing cell-type specific effects of dopamine on attentional modulation.