Central Autonomic Nervous System Research Articles

Functional MRI of the Brainstem for Assessing Its Autonomic Functions: From Imaging Parameters and Analysis to Functional Atlas

BackgroundThe brainstem is a crucial component of the central autonomic nervous (CAN) system. Functional MRI (fMRI) of the brainstem remains challenging due to a range of factors, including diverse imaging protocols, analysis, and interpretation.PurposeTo develop an fMRI protocol for establishing a functional atlas in the brainstem.Study TypeProspective cross‐sectional study.SubjectsTen healthy subjects (four males, six females).Field Strength/SequenceUsing a 3.0 Tesla MR scanner, we acquired T1‐weighted images and three different fMRI scans using fMRI protocols of the optimized functional Imaging of Brainstem (FIBS), the Human Connectome Project (HCP), and the Adolescent Brain Cognitive Development (ABCD) project.AssessmentThe temporal signal‐to‐noise‐ratio (TSNR) of fMRI data was compared between the FIBS, HCP, and ABCD protocols. Additionally, the main normalization algorithms (i.e., FSL‐FNIRT, SPM‐DARTEL, and ANTS‐SyN) were compared to identify the best approach to normalize brainstem data using root‐mean‐square (RMS) error computed based on manually defined reference points. Finally, a functional autonomic brainstem atlas that maps brainstem regions involved in the CAN system was defined using meta‐analysis and data‐driven approaches.Statistical TestsANOVA was used to compare the performance of different imaging and preprocessing pipelines with multiple comparison corrections (P ≤ 0.05). Dice coefficient estimated ROI overlap, with 50% overlap between ROIs identified in each approach considered significant.ResultsThe optimized FIBS protocol showed significantly higher brainstem TSNR than the HCP and ABCD protocols (P ≤ 0.05). Furthermore, FSL‐FNIRT RMS error (2.1 ± 1.22 mm; P ≤ 0.001) exceeded SPM (1.5 ± 0.75 mm; P ≤ 0.01) and ANTs (1.1 ± 0.54 mm). Finally, a set of 12 final brainstem ROIs with dice coefficient ≥0.50, as a step toward the development of a functional brainstem atlas.Data ConclusionThe FIBS protocol yielded more robust brainstem CAN results and outperformed both the HCP and ABCD protocols.Evidence Level2Technical EfficacyStage 1

The Role of Central Oxytocin in Autonomic Regulation

Oxytocin (OXT), a neuropeptide originating from the hypothalamus and traditionally associated with peripheral functions in parturition and lactation, has emerged as a pivotal player in the central regulation of the autonomic nervous system (ANS). This comprehensive ANS, comprising sympathetic, parasympathetic, and enteric components, intricately combines sympathetic and parasympathetic influences to provide unified control. The central oversight of sympathetic and parasympathetic outputs involves a network of interconnected regions spanning the neuroaxis, playing a pivotal role in the real-time regulation of visceral function, homeostasis, and adaptation to challenges. This review unveils the significant involvement of the central OXT system in modulating autonomic functions, shedding light on diverse subpopulations of OXT neurons within the paraventricular nucleus of the hypothalamus and their intricate projections. The narrative progresses from the basics of central ANS regulation to a detailed discussion of the central controls of sympathetic and parasympathetic outflows. The subsequent segment focuses specifically on the central OXT system, providing a foundation for exploring the central role of OXT in ANS regulation. This review synthesizes current knowledge, paving the way for future research endeavors to unravel the full scope of autonomic control and understand multifaceted impact of OXT on physiological outcomes.

Emotion Recognition From Multimodal Physiological Signals via Discriminative Correlation Fusion With a Temporal Alignment Mechanism.

Modeling correlations between multimodal physiological signals e.g., canonical correlation analysis (CCA) for emotion recognition has attracted much attention. However, existing studies rarely consider the neural nature of emotional responses within physiological signals. Furthermore, during fusion space construction, the CCA method maximizes only the correlations between different modalities and neglects the discriminative information of different emotional states. Most importantly, temporal mismatches between different neural activities are often ignored; therefore, the theoretical assumptions that multimodal data should be aligned in time and space before fusion are not fulfilled. To address these issues, we propose a discriminative correlation fusion method coupled with a temporal alignment mechanism for multimodal physiological signals. We first use neural signal analysis techniques to construct neural representations of the central nervous system (CNS) and autonomic nervous system (ANS). respectively. Then, emotion class labels are introduced in CCA to obtain more discriminative fusion representations from multimodal neural responses, and the temporal alignment between the CNS and ANS is jointly optimized with a fusion procedure that applies the Bayesian algorithm. The experimental results demonstrate that our method significantly improves the emotion recognition performance. Additionally, we show that this fusion method can model the underlying mechanisms in human nervous systems during emotional responses, and our results are consistent with prior findings. This study may guide a new approach for exploring human cognitive function based on physiological signals at different time scales and promote the development of computational intelligence and harmonious human-computer interactions.

Muslim Prayer (Salah), and Its Restorative Effect: Psychophysiological Explanation

Stress is the most common problem experienced by people across ages and is associated with poor psychological and physical health. Stress is related to emotional and mental states that can be seen psychologically, namely relaxed and focused, also physiologically through the central nervous system (CNS) and autonomic nervous system (ANS), both sympathetic (SNS) and parasympathetic nervous systems (PNS). Salah, as obligatory Muslim worship, is a coping strategy beneficial for psychological and other aspects, such as physical and neurological health. Salah has a restorative effect, such as reducing mental fatigue and stress, as explained by attention restorative theory (ART) and stress restorative theory (SRT). Salah can reduce stress, psychologically and physiologically, indicated by an increment in PNS [nuHF of heart rate variability (HRV), galvanic skin responses (GSR), heart rate (HR), and blood pressure (BP) activity and a decrease in SNS (nuLF and LF/HF of HRV) also increase of alpha brainwave which part of the central nervous system (CNS). In terms of focus, concentration, and awareness, salah is perceived as giving the worshiper a better mental state. In addition, salah increases the gamma power, which is part of CNS and related to awareness. Interestingly, the relaxation effect of salah is higher in the prostration position; also, reciting the Holy Quran while doing salah has higher effects on focus and attention than mimic salah. Apart from the obligation of salah, the psychological and physiological benefits of salah should make a Muslim pray obediently, and the finding that reciting the Holy Quran ayah during salah and prostration has a higher effect shows that remembering Allah is vital.

Concept: Electrical Cardiac Stimulation is Detected by the Cardiac Autonomic Nervous System with Possible Effects on the Vasovagal Reflex

Abstract A novel concept is described concerning the possible effect of right ventricular pacing stimulation being detected by the cardiac autonomic nervous system and through its afferent neuronal connection to the central autonomic nervous system (spinal cord) causing reversal or attenuation of the vasovagal reflex. This could be a direct effect of electrical stimulation or may occur by the known adverse consequences on ventricular synchrony induced by stimulation which could be right ventricular site and timing in the evolution of the vasovagal reflex dependent.

Differentiated choice of therapy regimen for acute poisoning with topical decongestants in children using a medical decision support system

Introduction. Acute poisoning in children is a major public health issue worldwide. Clinical Decision Support System (CDSS) is designed to improve quality of medical care by integrating scientific knowledge and research with information technology.
 Aim. Analyze clinical features of poisoning, identify unintentional differences in drug therapy and create a CDSS for individual choice of therapy for acute poisoning in children.
 Materials and methods. This study includes 178 children hospitalized with acute drug poisoning in Voronezh Regional Children's Clinical Hospital No. 1 from 2016 to 2022. The CDSS for poisoning with topical decongestants includes an algorithm for determination of the case severity depending on the patient's complaints, state of the central nervous system, cardiovascular system, and autonomic nervous system.
 Results. Most frequently poisoning in young children (under 5 years old) was caused by topical decongestants - 31 people (17.1%). After implementation of information technologies there was a significant decrease from 87.5% to 62.5% in the frequency of prescription of laboratory tests and infusion therapy in young children (p0.05). Decrease of glucocorticosteroid therapy in young children from 50% to 12.5% (p0,05).
 Conclusion. Information technologies implemented in the form of CDSS make it possible to carry out diagnosis and take therapeutic measures with consideration to individual features of the patient, reduce frequency of laboratory tests and drug load.

Complementary role of peripheral and central autonomic nervous system on insulin-like growth factor-1 activation to prevent fatty liver disease.

Insulin-like growth factor-1 (IGF-1) is involved in the pathology of non-alcoholic fatty liver disease (NAFLD) and ameliorates fatty infiltration in the liver. It is activated by growth hormone (GH); however, the role of GH-IGF-1 axis in NAFLD developmental phase has not been well identified. Therefore, in this study, we focused on the effect of IGF-1 in NAFLD pathology and GH excretion activation from the pituitary gland by peripheral autonomic neural pathways relaying liver-brain-gut pathway and by central neuropeptides. GH and IGF-1 levels were assessed in wild-type and melanocortin-4 receptor knockout mice upon the development of diet-induced NAFLD. The contribution of the peripheral autonomic nervous system connecting the liver-brain-gut axis was assessed by its blockade using capsaicin and that of the central nervous system was assessed by the expression of hypothalamic brain-derived neurotrophic factor (BDNF) and corticotropin-releasing factor (CRH), which activates GH release from the pituitary gland. In the NAFLD mouse models, the levels of GH and IGF-1 increased (p < .05). Further, hepatic fatty infiltration was suppressed even under peripheral autonomic nervous system blockade (p < .001), which inhibited gastric ghrelin expression. In mice with peripheral autonomic nervous blockade, hypothalamic BDNF and CRH were inhibited (p < .05), resulting in GH and IGF-1 excretion, whereas other neuropeptides of somatostatin and cortistatin showed no changes. These complementary effects were canceled in melanocortin-4 receptor knockout mice, which diminished BDNF and CRH release control. Our study demonstrates that the release of IGF-1 by the nervous system is a key factor in maintaining the pathological homeostasis of NAFLD, suggesting its therapeutic potential.

Assessment of ophthalmic vascular changes in fibromyalgia patients using optical coherence tomography angiography: is there a real pathology?

BackgroundFibromyalgia (FM) is a widespread musculoskeletal pain disorder. Although the pathogenesis of fibromyalgia is unknown, central neurotransmitter systems and autonomic nervous system abnormalities may play a critical role. Today, the diagnosis is made by clinical findings, and there is no objective, confirmatory tests. Studies examining ophthalmic structures in patients with fibromyalgia using optic coherence tomography (OCT) and optic coherence tomography angiography (OCTA) sought objective evidence of both the neurodegenerative and vascular processes of the disease. In the results of these few studies, some findings of retinal and vascular density changes were found. Materials and methodsIn this cross-sectional study, retinal superficial and deep vascular plexus density (SVP and DVP), choroid thickness, and choriocapillaris density were investigated in 42 patients with fibromyalgia and 42 healthy controls using OCTA. Results42 fibromyalgia patients, including 42 age- and gender-matched healthy controls, were enrolled in this study. Central macular thickness (CMT) was found to be significantly thinner in fibromyalgia patients than in healthy groups. Retinal SVP and DVP were evaluated. No significant differences were observed between FM patients and control subjects as regards DVP density in the macular area. However, SVP density significantly decreased in the superior and inferior quadrants of fibromyalgia patients compared to the healthy controls. There was no significant difference in choriocapillaris density and choroid thickness between the patients with fibromyalgia and the healthy group in all quadrants. ConclusionWe evaluated detailed ophthalmic vascular structures of patients with fibromyalgia using OCTA in our study. We found changes only superior and inferior quadrants of retinal superficial structures. There was no significant difference in other superficial vascular quadrants of the retina, deep vascular structures, and choriocapillaris density. On the other hand, the central macular thickness was thinner in FM patients. Therefore, these data show that the role of vascular processes in the pathogenesis of fibromyalgia is small, but thinner central macular thickness in FM may be significant as an objective finding of the disease

Signal processing and machine learning algorithm to classify anaesthesia depth

BackgroundPoor assessment of anaesthetic depth (AD) has led to overdosing or underdosing of the anaesthetic agent, which requires continuous monitoring to avoid complications. The evaluation of the central nervous system...

Contemporary Understanding of the Central Autonomic Nervous System in Fetal-Neonatal Transition

THE CRITICAL ROLE OF THE CENTRAL AUTONOMIC NERVOUS SYSTEM IN FETAL-NEONATAL TRANSITION: Sarah B. Mulkey, Adre dú Plessis Seminars in Pediatric Neurology Volume 28, December 2018, Pages 29-37 The objective of this article is to understand the complex role of the central autonomic nervous system in normal and complicated fetal-neonatal transition and how autonomic nervous system dysfunction can lead to brain injury. The central autonomic nervous system supports coordinated fetal transitional cardiovascular, respiratory, and endocrine responses to provide safe transition of the fetus at delivery. Fetal and maternal medical and environmental exposures can disrupt normal maturation of the autonomic nervous system in utero, cause dysfunction, and complicate fetal-neonatal transition. Brain injury may both be caused by autonomic nervous system failure and contribute directly to autonomic nervous system dysfunction in the fetus and newborn. The central autonomic nervous system has multiple roles in supporting transition of the fetus. Future studies should aim to improve real-time monitoring of fetal autonomic nervous system function and in supporting typical autonomic nervous system development even under complicated conditions.

Synchronous measurements of prefrontal activity and pulse rate variability during online video game playing with functional near-infrared spectroscopy

Interactions between the central nervous system (CNS) and autonomic nervous system (ANS) play a crucial role in modulating perception, cognition, and emotion production. Previous studies on CNS–ANS interactions, or heart–brain coupling, have often used heart rate variability (HRV) metrics derived from electrocardiography (ECG) recordings as empirical measurements of sympathetic and parasympathetic activities. Functional near-infrared spectroscopy (fNIRS) is a functional brain imaging modality that is increasingly used in brain and cognition studies. The fNIRS signals contain frequency bands representing both neural activity oscillations and heartbeat rhythms. Therefore, fNIRS data acquired in neuroimaging studies can potentially provide a single-modality approach to measure task-induced responses in the brain and ANS synchronously, allowing analysis of CNS–ANS interactions. In this proof-of-concept study, fNIRS was used to record hemodynamic changes from the foreheads of 20 university students as they each played a round of multiplayer online battle arena (MOBA) game. From the fNIRS recordings, neural and heartbeat frequency bands were extracted to assess prefrontal activities and short-term pulse rate variability (PRV), an approximation for short-term HRV, respectively. Under the experimental conditions used, fNIRS-derived PRV metrics showed good correlations with ECG-derived HRV golden standards, in terms of absolute measurements and video game playing (VGP)-related changes. It was also observed that, similar to previous studies on physical activity and exercise, the PRV metrics closely related to parasympathetic activities recovered slower than the PRV indicators of sympathetic activities after VGP. It is concluded that it is feasible to use fNIRS to monitor concurrent brain and ANS activations during online VGP, facilitating the understanding of VGP-related heart–brain coupling.

Heart Rate Variability as a Translational Dynamic Biomarker of Altered Autonomic Function in Health and Psychiatric Disease.

The autonomic nervous system (ANS) is responsible for the precise regulation of tissue functions and organs and, thus, is crucial for optimal stress reactivity, adaptive responses and health in basic and challenged states (survival). The fine-tuning of central ANS activity relies on the internal central autonomic regulation system of the central autonomic network (CAN), while the peripheral activity relies mainly on the two main and interdependent peripheral ANS tracts, the sympathetic nervous system (SNS) and the parasympathetic nervous system (PNS). In disease, autonomic imbalance is associated with decreased dynamic adaptability and increased morbidity and mortality. Acute or prolonged autonomic dysregulation, as observed in stress-related disorders, affects CAN core centers, thereby altering downstream peripheral ANS function. One of the best established and most widely used non-invasive methods for the quantitative assessment of ANS activity is the computerized analysis of heart rate variability (HRV). HRV, which is determined by different methods from those used to determine the fluctuation of instantaneous heart rate (HR), has been used in many studies as a powerful index of autonomic (re)activity and an indicator of cardiac risk and ageing. Psychiatric patients regularly show altered autonomic function with increased HR, reduced HRV and blunted diurnal/circadian changes compared to the healthy state. The aim of this article is to provide basic knowledge on ANS function and (re)activity assessment and, thus, to support a much broader use of HRV as a valid, transdiagnostic and fully translational dynamic biomarker of stress system sensitivity and vulnerability to stress-related disorders in neuroscience research and clinical psychiatric practice. In particular, we review the functional levels of central and peripheral ANS control, the main neurobiophysiologic theoretical models (e.g., polyvagal theory, neurovisceral integration model), the precise autonomic influence on cardiac function and the definition and main aspects of HRV and its different measures (i.e., time, frequency and nonlinear domains). We also provide recommendations for the proper use of electrocardiogram recordings for HRV assessment in clinical and research settings and highlight pathophysiological, clinical and research implications for a better functional understanding of the neural and molecular mechanisms underlying healthy and malfunctioning brain-heart interactions in individual stress reactivity and psychiatric disorders.

An Exploratory Study of the Effect of Tinnitus on Listening Effort Using EEG and Pupillometry.

Previous behavioral studies on listening effort in tinnitus patients did not consider extended high-frequency hearing thresholds and had conflicting results. This inconsistency may be related that listening effort is not evaluated by the central nervous system (CNS) and autonomic nervous system (ANS), which are directly related to tinnitus pathophysiology. This study matches hearing thresholds at all frequencies, including the extended high-frequency and reduces hearing loss to objectively evaluate listening effort over the CNS and ANS simultaneously in tinnitus patients. Case-control study. University hospital. Sixteen chronic tinnitus patients and 23 matched healthy controls having normal pure-tone averages with symmetrical hearing thresholds were included. Subjects were evaluated with 0.125 to 20 kHz pure-tone audiometry, Montreal Cognitive Assessment Test (MoCA), Tinnitus Handicap Inventory (THI), Visual Analog Scale (VAS), electroencephalography (EEG), and pupillometry. Pupil dilation and EEG alpha band in the "coding" phase of the sentence presented in tinnitus patients was less than in the control group (p < .05). VAS score was higher in the tinnitus group (p < .01). Also, there was no statistically significant relationship between EEG and pupillometry components and THI or MoCA (p > .05). This study suggests that tinnitus patients may need to make an extra effort to listen. Also, pupillometry may not be sufficiently reliable to assess listening effort in ANS-related pathologies. Considering the possible listening difficulties in tinnitus patients, reducing the listening difficulties, especially in noisy environments, can be added to the goals of tinnitus therapy protocols.

Central Autonomic Nervous System Balanced by Electroacupuncture in Hypertension

Overexcitation of sympathetic activity strongly related to increased blood pressure (BP) is decreased by electroacupuncture (EA). Reflex elevated BP response and elevated neuronal activity in the rostral ventrolateral medulla (rVLM), a central region for sympathetic outflow are reduced by stimulation of somatosensory nerves during a 30 min EA. However, it is unclear if the medullary nucleus ambiguus (NA) related to parasympathetic activity also is influenced by EA during elevated BP. In hypertensive subjects, EA therapy over deep peroneal and tibial nerves (ST36-37+SP6-7) decreases high BP. We hypothesize that a course of EA treatments decreases high BP by reducing rVLM and simultaneously increasing NA neuronal activity in hypertensive rats. Dahl salt-sensitive rats were fed either a standard rat diet or 4% salt rat diet developing hypertension. Normotensive control rats were acclimated to handling and restraining while Sham-EA (absence of electrical input to acupuncture needles) and EA treated hypertensive rats were acclimatized also to needling. Sham-EA or EA was given twice a week for 30 minutes in awake hypertensive rats for 5 weeks. BPs were measured with tail-cuff CODA system. At end of 10 weeks, tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) neuronal (NeuN) expressions were evaluated by immunohistochemistry as well as neuronal activity were determined by extracellular recordings in the rVLM and NA in Sham-EA, EA treated rats, and control rats. BP of control rats was at 130.3±1.7 mmHg (n=6) at end of experiment. BP significantly decreased by 25.9% in EA treated (138.04±1.8 mmHg, n=6) compared to Sham-EA (186.3±2.3 mmHg, n=7) hypertensive rats. Cardiovascular pre-sympathetic neuronal activity in rVLM significantly was decreased by 43% (1.33±0.10 to 0.75±0.13 sp/s, n=10) while the pre-parasympathetic activity in NA was increased by 96% (0.70±0.08 to 1.37±0.13 sp/s, n=12) in EA compared to Sham-EA treated hypertensive rats. Control rats rVLM activity was 0.23± 0.07 sp/s (n=4) and NA activity was 2.71±0.56 sp/s (n=5). Also, numbers of rVLM neurons expressing TH and NeuN were decreased (from 96 to 73) and NA neurons expressing ChAT and NeuN were increased (from 35 to 107) in Sham-EA compared to EA treated hypertensive rats. In normal control rats, rVLM showed 69 TH neurons and NA demonstrated 134 ChAT neurons. In conclusion, the BP lowering EA effect likely involved central autonomic rebalance by activating both sympathoinhibition and parasympathoexcitation. National Institute of Health National Center for Complementary &amp; Integrative Health Grant AT011306 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Shark Fin Electrocardiogram in the Intensive Care Unit.

HomeCirculationVol. 146, No. 14Shark Fin Electrocardiogram in the Intensive Care Unit Free AccessCase ReportPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessCase ReportPDF/EPUBShark Fin Electrocardiogram in the Intensive Care Unit Bin Zhang, PhD, Zhao-Wei Yin, MD and Wenbiao Chen, PhD Bin ZhangBin Zhang https://orcid.org/0000-0002-7590-3752 Department of Cardiovascular Disease and Clinical Experimental Center, Jiangmen Central Hospital, Jiangmen, Guangdong, China (B.Z.). *B. Zhang and Z.-W. Yin contributed equally. Search for more papers by this author , Zhao-Wei YinZhao-Wei Yin https://orcid.org/0000-0001-9051-1426 Peking University Health Science Center, Beijing, China (Z.-W.Y.). *B. Zhang and Z.-W. Yin contributed equally. Search for more papers by this author and Wenbiao ChenWenbiao Chen Correspondence to: Wenbiao Chen, PhD, No. 38, Jinglong Construction Road, Shenzhen, 518109, Guangdong, China. Email E-mail Address: [email protected] https://orcid.org/0000-0002-1028-6319 Department of Respiratory Medicine, People’s Hospital of Longhua, The Affiliated Hospital of Southern Medical University, Shenzhen, Guangdong, China (W.C.). Search for more papers by this author Originally published3 Oct 2022https://doi.org/10.1161/CIRCULATIONAHA.122.062034Circulation. 2022;146:1099–1102ECG ChallengeA 54-year-old woman was admitted to the intensive care unit with septic shock induced by intraabdominal infection. An initial physical examination revealed a body temperature of 38.6°C, a blood pressure of 82/56 mm Hg, a pulse rate of 109 beats per minute, and a respiratory rate of 26 breaths/minute. At admission, a 12-lead ECG was performed (Figure 1). Serum troponin I level was 2.02 ng/mL (normal value <0.10 ng/mL) and NT-proBNP (N-terminal pro–B-type natriuretic peptide) level was 5300 pg/mL (normal value <450 pg/mL). What are the important findings on the ECG? What is the most likely diagnosis? How would you manage the patient?Download figureDownload PowerPointFigure 1. Initial ECG at admission.Please turn the page to read the diagnosis.Response to ECG ChallengeThe initial ECG showed diffuse ST-segment elevations in leads I, II, III, aVF, and V3 through V6 (Figure 1), which suggested a diagnosis of anterior and inferior wall ST-segment–elevation myocardial infarction. However, ST-segment depressions in leads aVR and V1 were inconsistent with that diagnosis. The prominent ST-segment depression in aVR might reflect a ST-segment elevation in lead aVR, which faces the apical and inferolateral regions. Diffuse ST-segment elevations (most prominent in leads II and aVR) might reflect extensively distributed wall motion abnormalities centered around the apex, which extended beyond the perfusion territory of any single coronary artery. The ST-segment depression in lead V1 indicated that wall motion abnormalities did not involve the right ventricular anterior region and the right paraseptal region faced by lead V1.1,2 The V3 through V6 leads showed giant R waves (amplitude ≥1 mV) that merged with markedly elevated ST segments, which formed a triangular morphology known as the same configuration called shark-fin sign and lambda-wave pattern (Figure 1). This electrocardiographic presentation is characteristic of ST-segment–elevation myocardial infarction, where the QRS complex, the ST segment, and the T wave are fused in a unique complex. Although acute coronary ischemia is traditionally associated with a shark-fin sign, this unusual tracing is also occasionally found in takotsubo cardiomyopathy (TTC), associated with hemodynamic instability and shock.3 In addition, the rise in serum troponin I level was disproportionately lower than expected for the degree of left ventricular contractile impairment and the NT-proBNP level was much higher than typically observed in a myocardial infarction, which suggested a high degree of acute left ventricular dilation and myocardial stretch. The ECG and cardiac biomarkers provided a clue that this patient might have TTC. Confirmation of TTC diagnosis requires coronary angiography and left ventriculography. In this patient, coronary angiography revealed normal coronary arteries (Figure 2A and 2B) and left ventriculography showed systolic apical ballooning in the left ventricle (Figure 2C and 2D) with a low left ventricular ejection fraction of 38%, consistent with a diagnosis of TTC. TTC was the final diagnosis in this patient.Download figureDownload PowerPointFigure 2. Emergent coronary angiography and left ventriculography. A and B, Emergent coronary angiography showed no evidence of obstructive or spastic coronary disease. C and D, Left ventriculography revealed systolic apical ballooning in the apical region of the left ventricle.The patient was treated in an intensive care unit with a trachea cannula and mechanical ventilation. She was given empiric broad-spectrum antibiotics, intravenous fluids, and vasopressor support. The empiric antimicrobial therapy was replaced once the underlying pathogen was recognized and antimicrobial sensitivities were established. Systolic apical ballooning in the left ventricle was treated with levosimendan, a noncatecholamine inotrope that does not increase myocyte cyclic adenosine monophosphate or oxygen consumption. Six days later, the disease had abated and the ECG (Figure 3) showed resolution of ST-segment elevations in leads I, II, III, aVF, and V2 through V6; T-wave flatness in leads I, II, III, aVR, aVL, aVF, V5, and V6; T-wave inversion in leads V1 through V4; and mild QT prolongation. A repeat ultrasonic cardiogram 5 weeks after discharge showed resolution of left ventricular systolic function (left ventricular ejection fraction, 59%).Download figureDownload PowerPointFigure 3. ECG after resolution.TTC is characterized by systolic dysfunction typically localized in the apical aspect (81.7%) and less frequently localized in the midventricular aspect (14.6%), basal aspect (2.2%), or focal aspect (1.5%) of the left ventricle. The most accepted hypothesis to explain how TTC arises is an elevation in circulating catecholamines and stress hormones, typically related to physical or emotional stress. Sepsis, a state of severe physical stress, can raise catecholamine levels, which activates the central autonomic nervous system and causes calcium overload in cardiac myocytes, leading to stunning of the myocardium and precipitation of cardiomyopathy. The rather specific ECG changes in TTC are T-wave inversion, often deep and widespread, and substantial QT prolongation, usually developing 24 to 48 hours after the onset of symptoms or the precipitating stressful trigger. ST-segment elevation involving precordial leads is seen in ≈40% of cases. In our case, cardiac involvement was associated with sepsis caused by an intraabdominal infection. The shark-fin sign, described in high-level stressors like critical illness, is an uncommon electrocardiographic finding that typically results from the fusion of the QRS complex, ST segment, and T wave. A proposed mechanism of ST-segment elevation in TTC is a mismatch between endo-epicardial wall tension and stretch-activated channel activation, which eventually leads to a transmural repolarization gradient and hence a coved-type ST modification that mimics the ischemic shark-fin sign. Mounting evidence has associated this feature with increased risk of ventricular fibrillation and cardiogenic shock.3In a critically ill patient with shark-fin sign on ECG and septic shock, TTC needs to be considered, and TTC should be included in the differential diagnosis for patients with sepsis and ST elevation that mimics acute anterior ST-segment–elevation myocardial infarction.Article InformationSources of FundingNone.Disclosures None.Footnotes*B. Zhang and Z.-W. Yin contributed equally.Circulation is available at www.ahajournals.org/journal/circFor Sources of Funding and Disclosures, see page 1101–1102.Correspondence to: Wenbiao Chen, PhD, No. 38, Jinglong Construction Road, Shenzhen, 518109, Guangdong, China. Email [email protected]com

Insular functional connectivity in migraine with aura

IntroductionInsula plays an integrating role in sensory, affective, emotional, cognitive and autonomic functions in migraine, especially in migraine with aura (MA). Insula is functionally divided into 3 subregions, the dorsoanterior, the ventroanterior and the posterior insula respectively related to cognition, emotion, and somatosensory functions. This study aimed at investigating functional connectivity of insula subregions in MA.MethodsTwenty-one interictal patients with MA were compared to 18 healthy controls (HC) and 12 interictal patients with migraine without aura (MO) and were scanned with functional MRI during the resting state. Functional coupling of the insula was comprehensively tested with 12 seeds located in the right and left, dorsal, middle, ventral, anterior and posterior insula, by using a seed-to-voxel analysis.ResultsSeed-to-voxel analysis revealed, in MA, a strong functional coupling of the right and left antero-dorsal insula with clusters located in the upper cerebellum. The overlap of these cerebellar clusters corresponded to the vermis VI. These functional couplings were not correlated to duration of MA, frequency of MA attacks nor time since last MA attack, and were not found in MO.DiscussionThe anterior insula and superior cerebellum, including vermis VI, are components of the central Autonomic Nervous System (ANS) network. As these regions are involved in the control of cardiovascular parasympathetic tone, we hypothesize that this connectivity may reflect the cardiovascular features of MA.ConclusionThe anterior dorsal insula is connected with vermis VI in MA patients in the resting state. This connectivity may reflect the cardiovascular features of MA.Trial registrationNCT02708797.

Neurological Manifestations of Fabry Disease: Literature Review

BACKGROUND: Fabry disease (FD) or Anderson FD is a hereditary disease belonging to the group of lysosomal storage diseases caused by decreased or absent activity of the enzyme α-galactosidase A. Enzyme deficiency leads to accumulation of glycospholipids in the lysosomes of cells of various organs, including the heart, kidneys, nervous system, and vascular endothelium. The complexity of the diagnosis of FD is due to the variety of its symptoms, the simultaneous involvement of many organs and systems. At present, possible pathogenetic treatment of the disease is enzyme replacement therapy, but its effectiveness is reduced in the later stages of the disease, when there are irreversible abnormal changes in vital organs and systems. In this regard, an urgent task is the early diagnosis of FD. AIM: Determination of neurological manifestations of FD as well as clinical criteria for screening for FD. MATERIALS AND METHODS: We analyzed cohort studies, randomized controlled trials, systematic reviews and meta-analyses, case-control studies, and case series from scientific medical databases: PubMed, Web of Science, Google Scholar in Russian, and English languages. CONCLUSION: The authors found that lesions of the nervous system in FD are detected in more than 80% of patients and can manifest as isolated or combined lesions of both the central and peripheral and autonomic nervous systems.

Impact of Catheter Ablation on Brain Microstructure and Blood Flow Alterations for Cognitive Improvements in Patients with Atrial Fibrillation: A Pilot Longitudinal Study.

Atrial fibrillation (AF) predisposes patients to develop cognitive decline and dementia. Clinical and epidemiological data propose that catheter ablation may provide further benefit to improve neurocognitive function in patients with AF, but the underlying mechanism is poorly available. Here, we conducted a pilot prospective study to investigate whether AF ablation can alter regional cerebral blood flow (rCBF) and brain microstructures, using multimodal magnetic resonance imaging (MRI) technique. Eight patients (63 ± 7 years) with persistent AF underwent arterial-spin labeling (ASL) perfusion, 3D T1-structural images and cognitive test batteries before and 6 months after intervention. ASL and structural MR images were spatially normalized, and the rCBF and cortical thickness of different brain areas were compared between pre- and 6-month post-treatment. Cognitive–psychological function was improved, and rCBF was significantly increased in the left posterior cingulate cortex (PCC) (p = 0.013), whereas decreased cortical thickness was found in the left posterior insular cortex (p = 0.023). Given that the PCC is a strategic site in the limbic system, while the insular cortex is known to play an important part in the central autonomic nervous system, our findings extend the hypothesis that autonomic system alterations are an important mechanism explaining the positive effect of AF ablation on cognitive function.

A new framework for modeling the bidirectional interplay between brain oscillations and cardiac sympathovagal activity.

The study of functional brain-heart interplay (BHI) aims to describe the dynamical interactions between central and peripheral autonomic nervous systems. Here, we introduce the Sympathovagal Synthetic Data Generation Model, which constitutes a new computational framework for the assessment of functional BHI. The model estimates the bidirectional interplay with novel quantifiers of cardiac sympathovagal activity gathered from Laguerre expansions of RR series (from the ECG), as an alternative to the classical spectral analysis. The main features of the model are time-varying coupling coefficients linking Electroencephalography (EEG) oscillations and cardiac sympathetic or parasympathetic activity, for either ascending or descending direction of the information flow. In this proof-of-concept study, functional BHI is quantified in the direction from-heart-to-brain, on data from 16 human volunteers undergoing a cold-pressor test. Results show that thermal stress induces heart-to-brain functional interplay originating from sympathetic and parasympathetic activities and sustaining EEG oscillations mainly in the δ and γ bands. The proposed computational framework could provide a viable tool for the functional assessment of the causal interplay between cortical and cardiac sympathovagal dynamics.

Insula Response to Interoception Is Inversely Correlated with Trait Mindfulness, Self-compassion, and Migraine Frequency in Patients with Episodic Migraine

Migraine is a highly prevalent chronic pain disorder that is characterized by sensitization and dysregulation of the central autonomic nervous system. Interoception is the sensing of signals originating from within the body, and is altered in chronic pain conditions including episodic migraine. The relationship between brain mechanisms of interoceptive awareness and clinical measures of migraine severity has not been fully explored. We used functional MRI to investigate whether insula response to interoceptive awareness is associated with clinical and behavioral measures in patients with episodic migraine. In this study, 18 patients with episodic migraine (17 F, 1 M, mean age ± SD: 41.3 ± 13.1 years). All patients underwent a 3-Tesla fMRI scan and completed a novel interoceptive awareness task (TR=2s,). During the task, patients were asked to focus on and rate the intensity of sensation for two interoceptive conditions (heart and lungs), as well as two exteroceptive conditions (sight and sound). Participants completed survey measures related to interoception, mindfulness, self-compassion, and migraine frequency. Bold response to the interoception - exteroception task contrast (z > 3.1, p = 0.05 corrected) included two clusters overlapping with bilateral mid-insula (left center: x=-46,y=-1.5,z=7.4, 2615 voxels, 33% overlap with anatomical insula, right center: x=44,y=7.1,z=3.9, 1332 voxels, 46% overlap with anatomical insula). Significant inverse associations were observed between insula response to interoception and SCS (r = -0.65, p = 0.003), Freiburg Mindfulness (r = -0.68, p = 0.002), and the number of migraine days reported within 30 days prior to the MRI scan (r = -0.64, p = 0.004) (all significant after Bonferroni correction). Patients with episodic migraine showed insula response during a novel interoceptive awareness task, and this response was inversely correlated with recent migraine frequency, and measures of both trait mindfulness and self-compassion. Grant support from NIH NCCIH P01AT009965.