Central Autonomic Dysregulation Research Articles

Central autonomic regulation assessed by pupillary light reflex is impaired in children with attention deficit hyperactivity disorder.

It is assumed that the Attention Deficit Hyperactivity Disorder is associated with the central autonomic dysregulation, however, the studies are rare. Analysis of pupillary light reflex represents a non-invasive tool to provide information related to the central autonomic regulation; thus, we aimed to evaluate potential disturbances in the central autonomic integrity using pupillary light reflex examination in Attention Deficit Hyperactivity Disorder. We have examined 20 children with Attention Deficit Hyperactivity Disorder (10 boys, 13.0+/-2.3 years) and 20 age/gender-matched healthy subjects. Pupillary light reflex was examined at rest for both eyes using Pupillometer PLR-2000 (NeurOptics, USA). Evaluated parameters were: diameter of the pupil before the application of light stimulus and after illumination at the peak of the constriction, the percentual change of the pupil diameter during constriction, average constriction velocity, maximum constriction velocity and average dilation velocity. We found significantly lower percentual change of the pupil diameter during constriction for both eyes in Attention Deficit Hyperactivity Disorder group compared to controls (right eye: -25.81+/-1.23 % vs. -30.32+/-1.31 %, p<0.05, left eye: -25.44+/-1.65 % vs. -30.35+/-0.98 %, p<0.05). The average constriction velocity and maximum constriction velocity were significantly shortened in left eye in Attention Deficit Hyperactivity Disorder group compared to controls (p<0.05). Our findings revealed altered pupillary light reflex indicating abnormal centrally-mediated autonomic regulation characterized by parasympathetic underactivity associated with relative sympathetic predominance in children suffering from Attention Deficit Hyperactivity Disorder.

Oculometric behavior assessed by pupil response is altered in adolescent depression.

Oculometric behaviour assessed by pupil response provides important information about central autonomic activity and emotional regulation. However, studies regarding pupil response to emotional stimuli in adolescent depression are rare. We aimed to study emotional-linked pupil response in adolescent depression. Twenty depressive adolescents (average age: 15.4+/-1.2 years) and 20 age/gender-matched healthy subjects were examined. Average pupil diameter assessed by eye-tracking and pupillary light reflex were evaluated during protocol - baseline, free-view task, recovery phase. Regarding right eye, significantly greater initial pupil diameter and pupil dilation to positive pictures free-viewing (p=0.013, p=0.031, respectively), significantly slower average and maximum constriction velocity in baseline and positive pictures free-viewing (p=0.036, p=0.050, p=0.021, p=0.015, respectively), significantly slower maximum constriction velocity in recovery phase (p=0.045), and significantly faster average dilation velocity in negative pictures free-viewing (p=0.042) were observed in depressive group. Regarding left eye, significantly lower constriction percentual change in negative pictures free-viewing (p=0.044) and significantly greater baseline pupil diameter and pupil diameter at the peak of constriction in positive vs. negative pictures free-viewing (p=0.002, p=0.015, respectively) were observed in depressive group. Our study revealed discrete central autonomic dysregulation - parasympathetic hypoactivity associated with relative sympathetic dominance influenced by impairments in emotional processing already in adolescent depression.

Cardiorespiratory Coupling Analysis Based on Entropy and Cross-Entropy in Distinguishing Different Depression Stages.

AimsThis study used entropy- and cross entropy-based methods to explore the cardiorespiratory coupling of depressive patients, and thus to assess the values of those entropy methods for identifying depression patients with different disease severities.MethodsElectrocardiogram (ECG) and respiration signals from 69 depression patients were recorded simultaneously for 5 min. Patients were classified into three groups according to the Hamilton Depression Rating Scale (HDRS) scores: group Non-De (HDRS 0–7), Mid-De (HDRS 8–17), and Con-De (HDRS >17). Sample entropy (SEn), fuzzy measure entropy (FMEn) and high-frequency power (HF) were computed on the original RR interval time series and breath-to-breath interval time series. Cross sample entropy (CSEn) and cross fuzzy measure entropy (CFMEn) were computed on interval time series resampled at 2 Hz and 4 Hz, respectively. The difference among three patient groups and correlation between entropy values and HDRS scores were analyzed by statistical analysis. Surrogate data were also employed to confirm the validation of entropy measures in this study.ResultsA consistent increasing trend has been found among most entropy measures from Non-De, to Mid-De, and to Con-De groups, and a significant (p < 0.05) difference in FMEn of RR intervals exists between Non-De and Mid-De or Con-De groups. Significant differences have been also found in all cross entropies, between Non-De and Con-De groups and between Mid-De and Con-De groups. Furthermore, significant correlations also exist between HDRS scores and FMEn of RR intervals (R = 0.24, p < 0.05), CSEn at 4 Hz (R = 0.26, p < 0.05) or 2 Hz (R = 0.28, p < 0.05) resampling, and CFMEn at 4 Hz (R = 0.31, p < 0.01) or 2 Hz (R = 0.30, p < 0.05) resampling. A significant difference of cardiorespiratory coupling parameters between different depression stages and significant correlations between entropy measures and depression severity both indicate central autonomic dysregulation in depression patients and reflect varying degrees of vagal modulation reduction among different depression levels. Analysis based on surrogate data confirms that the non-linear properties of the physiological signals played a major role in depression recognition.ConclusionThe current study demonstrates the potential of cardiorespiratory coupling in the auxiliary diagnosis of depression based on the entropy method.

Valsalva maneuver unveils central baroreflex dysfunction with altered blood pressure control in persons with a history of mild traumatic brain injury.

BackgroundPatients with a history of mild TBI (post-mTBI-patients) have an unexplained increase in long-term mortality which might be related to central autonomic dysregulation (CAD). We investigated whether standardized baroreflex-loading, induced by a Valsalva maneuver (VM), unveils CAD in otherwise healthy post-mTBI-patients.MethodsIn 29 healthy persons (31.3 ± 12.2 years; 9 women) and 25 post-mTBI-patients (35.0 ± 13.2 years, 7 women, 4–98 months post-injury), we monitored respiration (RESP), RR-intervals (RRI) and systolic blood pressure (BP) at rest and during three VMs. At rest, we calculated parameters of total autonomic modulation [RRI-coefficient-of-variation (CV), RRI-standard-deviation (RRI-SD), RRI-total-powers], of sympathetic [RRI-low-frequency-powers (LF), BP-LF-powers] and parasympathetic modulation [square-root-of-mean-squared-differences-of-successive-RRIs (RMSSD), RRI-high-frequency-powers (HF)], the index of sympatho-vagal balance (RRI LF/HF-ratios), and baroreflex sensitivity (BRS). We calculated Valsalva-ratios (VR) and times from lowest to highest RRIs after strain (VR-time) as indices of parasympathetic activation, intervals from highest systolic BP-values after strain-release to the time when systolic BP had fallen by 90 % of the differences between peak-phase-IV-BP and baseline-BP (90 %-BP-normalization-times), and velocities of BP-normalization (90 %-BP-normalization-velocities) as indices of sympathetic withdrawal.We compared patient- and control-parameters before and during VM (Mann-Whitney-U-tests or t-tests; significance: P < 0.05).ResultsAt rest, RRI-CVs, RRI-SDs, RRI-total-powers, RRI-LF-powers, BP-LF-powers, RRI-RMSSDs, RRI-HF-powers, and BRS were lower in patients than controls. During VMs, 90 %-BP-normalization-times were longer, and 90 %-BP-normalization-velocities were lower in patients than controls (P < 0.05).ConclusionsReduced autonomic modulation at rest and delayed BP-decrease after VM-induced baroreflex-loading indicate subtle CAD with altered baroreflex adjustment to challenge. More severe autonomic challenge might trigger more prominent cardiovascular dysregulation and thus contribute to increased mortality risk in post-mTBI-patients.

Altered cardiorespiratory coupling in young male adults with excessive online gaming

IntroductionThis study aimed to investigate changes in heart rate variability and cardiorespiratory coupling in male college students with problematic Internet use (PIU) excessive gaming type during action video game play to assess the relationship between PIU tendency and central autonomic regulation. MethodElectrocardiograms and respiration were simultaneously recorded from 22 male participants with excessive online gaming and 22 controls during action video game play. Sample entropy (SampEn) was computed to assess autonomic regularity, and cross-SampEn was calculated to quantify autonomic coordination. ResultsDuring video game play, reduced cardiorespiratory coupling (CRC) was observed in individuals with PIU excessive gaming type compared with controls, implicating central autonomic dysregulation. The PIU tendency was associated with the severity of autonomic dysregulation. ConclusionThese findings indicate impaired CRC in PIU excessive gaming type, which may reflect alterations of central inhibitory control over autonomic responses to pleasurable online stimuli.

Cognitive and autonomic dysfunction in presymptomatic and early Huntington’s disease

Huntington's disease is characterized by disorders of movement, cognition and behavior. Individuals with Huntington's disease display aberrant changes in the autonomic nervous system that are detected even before the onset of other symptoms. Subtle cognitive dysfunction may start before other clinical manifestations. The aim of the present study was to investigate the autonomic nervous system response to mental arithmetic and the relationship between the autonomic and cognitive/motor function in presymptomatic and early Huntington's disease. We examined 15 presymptomatic Huntington's disease gene carriers (PHD), 15 early Huntington's disease patients (EHD) and 30 healthy controls. PHD and EHD groups were determined according to Unified Huntington's Disease Rating Scale (UHDRS) motor score. ECG, heart rate, systolic and diastolic blood pressure, and cutaneous laser Doppler flux were measured during rest and during a simple mental arithmetic test. UHDRS cognitive test battery was applied to determine cognitive dysfunction. During mental arithmetic, the heart rate of PHD/EHD increased significantly less than that of controls. Decreased microvascular response to mental arithmetic was found in EHD. Significant correlations for the PHD/EHD group were found between laser Doppler flux response and Symbol Digit Modalities Test score, and between laser Doppler flux response and UHDRS motor score. It seems that central autonomic dysregulation of cardiovascular system in Huntington's disease goes along with the degeneration of other central neuronal systems. This finding is relevant as it could enable simple and noninvasive testing of disease progression.

Abstract 19352: Obstructive Sleep Apnea Impairs the Time Delay of the Baroreflex Control and the Oscilattory Pattern of the Sympathetic Activity in Patients with Metabolic Syndrome

Background: Incidence and oscillatory pattern of muscle sympathetic nerve activity (MSNA) depends on the magnitude (sensitivity) and time delay of the arterial baroreflex. In metabolic syndrome (MetS), the obstructive sleep apnea (OSA) exacerbates the MSNA and baroreflex control of heart rate. Unknown is the impact of MetS and OSA on oscillatory pattern of MSNA and time delay of the baroreflex control of MSNA in MetS patients. We tested the hypotheses that: 1) MetS would impair these autonomic functions; 2) OSA would impair even further these autonomic functions. Methods and Results: Thirty-nine never-treated MetS patients (ATP III) were allocated in two groups according to the presence of OSA (MetS+OSA, n=17 and MetS-OSA, n=22). Twelve aged-paired healthy subjects were enrolled in the study as control group (C). OSA (apnea-hypopnea index&gt;15 events/hour) was determined during a polysomnography. We recorded MSNA (microneurography), blood pressure (beat-to-beat basis) and HR (ECG), during 10 min. Oscillatory patterns of MSNA, HR and systolic arterial pressure were evaluated by autoregressive spectral analysis. The baroreflex control of MSNA (gain and time delay), were evaluated by bivariate autoregressive analysis. Patients with MetS+OSA had increased high frequency band of MSNA (HF MSNA , 60±3 vs. 49±2 and 37±2 n.u., P&lt;0.001) and decreased low frequency band of MSNA (LF MSNA , 40±3 vs. 51±2 and 63±2 nu, P&lt;0.001) compared to MetS-OSA and C. The gain of the baroreflex control of MSNA was lower in MetS+OSA compared MetS-OSA and C (13±1 vs. 30±3 and 43±3 a.u./mmHg, P&lt;0.001). The time delay of the baroreflex control of MSNA was augmented in MetS+OSA compared to MetS-OSA and C (6±0.3 vs. 4±0.3 and 3±0.2 s, P&lt;0.001). MetS-OSA patients showed increased HF MSNA (P&lt;0.001) and decreased LF MSNA (P&lt;0.001) compared with C. And, the gain of the baroreflex control of MSNA was lower in MetS-OSA than in C groups (P&lt;0.001). Conclusions: MetS reduces the oscillatory pattern of MSNA and the gain of the baroreflex control of MSNA. OSA exacerbates these dysfunctions and further increases the time delay of the baroreflex control of MSNA in these patients. These central autonomic dysregulation of sympathetic modulation may have important clinical implications in patients with MetS+OSA.

P1.24 Orthostatic challenge identifies subtle sympathetic cardiac dysfunction in patients after mild traumatic brain-injury

McMillan and Teasdale showed in a prospective seven-year follow-up study of patients with mild traumatic brain injury (MTBI) significantly increased mortality rates with up to 7-times higher risk of mortality than in the average population [1]. The pathomechanisms causing increased death rates are unknown but might be related to central autonomic dysregulation due to the brain injury. Clinically overt signs or symptoms of autonomic dysfunction may be missing after MTBI. However, maneuvers activating the central autonomic modulation, such as orthostatic challenge with baroreflex activation, might unveil mild centrally caused autonomic dysfunction after TBI.

Abstract 4439: Insular Cortex Atrophy as an Independent Determinant of Disrupted Diurnal Rhythm of Ambulatory Blood Pressure in Elderly Hypertension

Recently, insular cortex (Ic) is suggested to be a key site in limbic-autonomic integration. Association of Ic damage with diurnal blood pressure (BP) variation disruption, higher level of brain natriuretic peptide (BNP) and catecholamine were reported. We examined the relationship of Ic volume with ambulatory BP measures and these biomarkers. Amubulatory BP monitoring and brain MRI were performed in 55 elderly hypertensives. Right and left Ic volumes were measured using Intensity Contour-Mapping Algorithm. BNP, adrenaline and noradrenaline concentration were evaluated. Subjects were classified into Ic-atrophy group (n=14) and non-atrophy group (n=41) based on total Ic volume (right and left side) of 12.6 cm 3 (lowest quartile). In Ic-atrophy group, 24hr (144.5 vs 134.2 mmHg, p=0.032), sleep (143.4 vs 127.2 mmHg, p=0.002) systolic BP (SBP), nocturnal SBP dipping (1.30 vs 8.54 %, p=0.027) and BNP (60.6 vs 28.1 pg/ml, p=0.008) were significantly, and noradrenaline (373.5 vs 296.5 pg/ml, p=0.084) was marginally different from those in non-atrophy group. Right Ic volume was significantly correlated with 24hr (r=−0.271, p=0.046), sleep (r=−0.420, p=0.001) SBP, nocturnal SBP dipping (r=0.311, p=0.021) and noradrenaline (r=−0.334, p=0.013), while left Ic volume with 24hr (r=−0.279, p=0.039), sleep (r=−0.498, p=0.0001) SBP, nocturnal SBP dipping (r=0.409, p=0.002) and BNP (r=−0.363, p=0.006). In multiple linear regression analysis adjusted for age, gender and body mass index, left Ic volume was significantly negatively associated with sleep SBP (p=0.008) and BNP (p=0.001), and positively with nocturnal SBP dipping (p=0.044). In elderly hypertensives, predominant left Ic atrophy was significantly associated with sleep SBP measures and BNP. Ic damage, specifically in the left side, may partly contribute to disruption of diurnal ambulatory BP rhythm as well as cardiac function via central autonomic dysregulation.

Increased QT dispersion in breath‐holding spells

Breath‐holding spells (BHS) in children can be a frightening and clinically challenging paroxysmal, non‐epileptic childhood disorder. The pathophysiology has been found to incorporate central nervous system dysregulation in addition to an underlying genetic predisposition. Akalin and colleagues found group differences (BHS versus controls) in QT dispersion and QTc dispersion. These differences, however, may have been affected mainly by normal sinus arrhythmia from the predominant cyanotic BHS cohort.Conclusion: The subtle differences measured in the current study between pallid and cyanotic breath‐holder groups, in terms of increased QTc dispersion in the pallid group, may represent an additional factor impacted upon by the resting state of underlying central autonomic dysregulation.

Evidence for autonomic dysregulation in the irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by chronic abdominal pain and visceral hypersensitivity. In this study, resting blood pressure and heart rate were recorded in 20 IBS patients and 23 controls. We assessed pain intensity and unpleasantness to visceral and cutaneous stimuli using rectal distension and immersion of the foot in hot water. Mean resting heart rate was higher in IBS patients compared to controls. IBS patients rated pain intensity and unpleasantness to visceral and cutaneous stimuli significantly higher than controls. In IBS patients, blood pressure was significantly inversely associated with visceral pain and only weakly and positively associated with cutaneous pain; there were no relationships in controls. Sex and anxiety did not explain these relationships. In conclusion, we found evidence suggestive of central autonomic dysregulation in IBS patients.